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Résumés des prochains séminaires
Proprioception and spinal circuits for postural control
Niccolò ZAMPIERI, MDC Berlin, Germany
I will talk about recent work aimed at unveiling propriospinal neuron muscle identity and spinal circuits involved in postural control. We recently identified the determinants at the basis of propriospinal neuron muscle subtype identity. This discovery allowed us to selectively study proprioceptors controlling the activity of back muscles and identify molecular mechanisms controlling their identity. This work paves the way for dissecting proprioceptive circuits specifically controlling the activity of muscles with different biomechanical functions and their roles in the construction of a body map that is used for the generation of coordinated and adaptable movement. In addition, I will discuss how an evolutionary ancient interoceptive system that is conserved among all vertebrates has surprising functions in mammalian motor control. Altogether these data highlight the importance of different spinal circuits in integrating multiple source of sensory information to precisely control movement, balance and posture.
Wednesday 30 June 2021 à 11h30, Salle de conférence.
Principles and Mechanisms of Genome Diversification & Integrity
Michela Di Virgilio, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany
Genomic DNA is constantly under the assault of both endogenous and exogenous damaging sources. As a result, our cells experience a multitude of DNA lesions every day. Among all the different types of DNA damage, DNA double-strand breaks (DSBs) represent one of the most dangerous lesions since they may lead to cancer-prone genome alterations. DSBs arise following exposure to ionizing radiation or radio-mimetic chemicals, but they are also generated as a by-product of normal cellular metabolism, with the majority of spontaneous DSBs originating during DNA replication. In addition to these accidental breaks, DSBs can be introduced in a programmed manner as intermediates of physiological processes such as Class Switch Recombination (CSR) in B lymphocytes, a deletional recombination reaction that changes the constant region of the antibody molecule, altering its effector function. Accurate repair of both accidental and programmed DSBs is therefore crucial to ensure both the preservation of genome integrity and the generation of genome diversity. The research in my laboratory aims at addressing a fundamental question in Life Sciences: What are the molecular mechanisms that ensure both the integrity and diversity of our genome by modulating DSB formation and by steering their repair towards the appropriate physiological outcome? We employ mature B lymphocytes as ideal model system since in addition to experiencing programmed DNA breaks during CSR, these cells are highly proliferative and therefore susceptible to stochastic replication-associated damage, thus allowing us to comprehensively investigate the mechanisms ensuring genome diversity and stability, and their relationship.
Tuesday 29 June 2021 à 11h30, Salle de conférence.
Neurophysiological substrates for gaze stabilization during passive movement and locomotion
Mathieu Beraneck (CNRS UMR 8002, France)
All vertebrates share the need to stabilize the visual field during motion with rapid counteracting eye adjustments. Gaze control largely results from the sensory-motor transformation which primarily depends on the integration of visual and vestibular inputs. The optokinetic and vestibulo-ocular reflex are known to both contribute to gaze stabilization during passive, externally applied movements. During active movement however, sensory-motor pathways are supplemented by other neural signals. During this talk, I will first illustrate the differential organization of central vestibular pathways by focusing on the subpopulations of neurons responsible for visuo-vestibular integration and implicated in the vestibulo-ocular reflex (VOR) pathway and its adaptation. I will then present data that demonstrate in both xenopus and mice that during locomotion, an efferent copy signal originating from spinal-CPG participates early on to gaze control.
Monday 14 June 2021 à 11h, Visioconférence.
Quantification de comportement chez l’homme
Danping Wang (Plateforme d’Etude de la sensorimotricité)
exemples de projets scientifiques biomécaniques, physiologiques, cognitifs, de perception, de rééducation et de prévention avec des sujets sains, des patients et des sportifs
Thursday 10 June 2021 à 14h30, Visioconférence.
From prion diseases to Alzheimer’s disease: convergence of neurodegeneration mechanisms
Benoit Schneider (INSERM UMR-S1124, France)
Although amyloid-based neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, prion diseases… display distinct etiologies and clinical manifestations, it is more and more suspected the occurrence of common mechanisms of neurodegeneration. Starting from prion diseases, we uncovered a neurodegenerative signaling cascade that is common to prion and Alzheimer’s diseases. In this cascade, two kinases ROCK (for RhoA-associated kinases) and PDK1 (for 3-phosphoinositide-dependent kinase-1) provoke the neutralization of the neuroprotective α-secretase TACE (ADAM17). This amplifies the production of pathogenic prions PrP^Sc in prion diseases and beta-amyloid (Aβ) peptides in Alzheimer’s disease and renders diseased neurons highly vulnerable to TNFα injury. We recently showed that the deregulation of the PDK1-TACE pathway by PrP^Sc is also at the root of Aβ overproduction in prion diseases. Accumulated Aβ can deposit and form plaques in the brain of prion-infected mice, but only when a seed of trimers of Aβ is co-transmitted with PrP^Sc , which introduces trimers of Aβ as seeding and replicating entities. The consequence of brain Aβ deposition is an anticipated death of prion-infected mice because of the onset of a mixed PrP^Sc /Aβ pathology. This presentation will detail the mechanisms sustaining deregulation of the ROCK-PDK1-TACE pathway in prion and Alzheimer’s diseases and define whether targeting the ROCK/PDK1 kinases duo would be a novel therapeutic option for both prion and Alzheimer’s diseases and possibly other amyloid-based neurodegenerative diseases.
Monday 31 May 2021 à 11h, Visioconférence.
Liver X Receptor: a key player in myelination process and remyelination after injuries
Charbel Massaad (Inserm UMR 1124, France)
The peripheral nervous system is characterized by a unique symbiotic relationship between nerve fibers and their associated myelinating glial cells, the Schwann cells, which ensure axonal function and rapid nerve conduction. During peripheral nerve development, Schwann cells undergo a sequential developmental lineage transition from Schwann cell precursors to immature and finally myelinating Schwann cells, and any perturbation of Schwann cell lineage progression entails severe impairment of motor and sensory function. Importantly, many key regulators of SC development remain crucial for the generation and differentiation of the Schwann cell repair cell, which drives peripheral nerve regeneration. We identified an essential novel role for the liver X receptor ß (LXRß), a member of the nuclear receptor family of transcription factors and regulator of lipid metabolism, in early SC development. We showed that this receptor is involved in myelination process in the central and peripheral nervous systems. Furthermore, it plays a crucial role in the regulation of redox homeostasis in the nerve. Its activation alleviates from oxidative stress elicited by diabetic injuries in the nerve, leading to a protection from diabetic neuropathies. When we conditionally ablated LXRß specifically in SC precursors at embryonic day 12.5 (E12.5), peripheral nerves showed a developmental arrest at early embryonic stages and, postnatally, a dramatically reduced SC number along with a complete absence of myelinated axons. LXRß mutant mice developed a severe limb paralysis and died prematurely at the age of 7 months. The presentation will provide novel insight into the fundamental, yet unexplored role of LXRβ in Schwann cell development and regeneration and will open new therapeutic perspectives based on LXR modulation. Indeed, as this nuclear receptor constitutes a hub of lipid metabolism, cholesterol homeostasis, redox status stabilization and Schwann cell development, we propose that LXR signaling can be considered as a major regulator in peripheral nerve glial cell function, and hence provides a promising targetable pathway for treating PNS myelin-related diseases.
Monday 10 May 2021 à 11h, Visioconférence.
A sequential strategy for multiphoton actuation and recording of neuronal membrane voltage in awake animals
Stéphane Dieudonné, IBENS, Ecole Normale Supérieure, CNRS UMR 8197, INSERM U1024, Paris, France
Technologies for recording and manipulating neuronal membrane potential /in vivo/ in defined neuronal populations with high fidelity will be essential to understand how information is represented, processed, and propagated in the brain. Genetically encoded voltage indicators (GEVIs) and optogenetic actuators are especially promising as they can be expressed in defined cell types and are compatible with long-term chronic imaging /in vivo/. Optical recording and actuation of cellular voltage /in vivo/, however, suffers from limitations of both speed and sensitivity inherent in current indicators and imaging modalities. /In vivo/2P excitation of membrane proteins has been limited by three main factors: the low number of membrane proteins within a 2P focal volume, the low frame rate of standard 2P imaging and the possible imaging artefacts linked to brain motion in awake behaving mice. To address these three issues, we have developed light patterning strategies based on the acousto-optic technology. These strategies combine fast scanning (resonant rate), fast random-access (100 kHz- 1 MHz), holographic shaping of the focal volume and beam multiplexing. We demonstrate 10 kHz random-access voltage recordings from ensembles of neurons in awake behaving mice. Using ASAP3, a newly developed fast GEVI, we report single spike detection with sub-millisecond precision and subthreshold membrane potential recordings with cellular resolution deep in the cortex and hippocampus of awake mice. We show activation of the optogenetic actuator ChR2 at reduced laser power and with equivalent XY and Z resolution. Finally, we present new developments for 3D imaging and stimulation and demonstrate GCaMP6 calcium recording of neurons at different laminar positions within a 400x400x400 µm volume of mouse sensory cortex at 1 kHz sampling speed.
Friday 6 November 2020 à 11h30, Salle de conférence.
Exploratory behavior, individual trait and nicotine addiction: the role of dopamine
Philippe Faure, IBPS– Paris – France
Consistent individual differences in behaviours represent an ubiquitous feature in animal populations. These behavioural differences among individuals define personality and have been linked to the susceptibility to addiction. Indeed, the susceptibility to develop drug addiction differs substantially between individuals and some traits that characterize an individual, such as impulsivity, exploration or novelty seeking, have been shown to represent a predictive factor for the addictive properties of drugs. The presentation will explore the relationship between the dopaminergic system, the social context and the interindividual variability in behavioural traits and in particular in exploratory behaviour.
Friday 16 October 2020 à 11h30, Salle de conférence.
Optogenetics for vision restoration: toward clinical trials
Gregory Gauvain, Institut de la Vision – Paris – France
Using vector and genetic constructs most suitable for vision restoration in patients with retinopathies, we have demonstrated temporal resolution compatible with highly dynamic visual scenes and a visual acuity above legal blindness.
Friday 9 October 2020 à 11h30, Salle de conférence.
The neuroscience of why flies are people too!
Bassem Hassan, Institut du cerveau et de la moelle épinière (ICM) – Paris
The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using Drosophila melanogaster, we demonstrate a link between stochastic variation in brain wiring and behavioral individuality.
Friday 2 October 2020 à 11h30, Salle de conférence.
Schwann cell metamorphosis in type 1 neurofibromatosis
Piotr Topilko, Institut Mondor de Recherche Biomédicale, Hôpital Henri Mondor, France
Neurofibromatosis type 1 (NF1) is one of the most common (1/3000 births) rare genetic disorders caused by mutations in the /NF1/tumor suppressor gene. Nearly all NF1 patients develop benign nerve sheath tumors called neurofibromas (NFs) whichnumbermay reachintothethousands. In addition, some NFs progress into malignant peripheral nerve sheath tumors (MPNST) that are invariably lethal. Despite important advances in deciphering mechanisms driving development of NFs and their malignant transformation there is still no treatment options to block development of neurofibromas or to prevent their malignant transformation. In this context we have set up unique GEM model that faithfully recapitulates development of benign and malignant neurofibromas. Exploring this model allowed us to perform important discoveries concerning the cells at the origin of NFs, the role of inflammation in development of those tumors, the new mechanism driving malignant transformation and pave the way for development of new therapeutics to defeat this devastating disease.
Monday 28 September 2020 à 11h, Salle de conférence.
Evaluation of the corticofugal hypothesis in ALS
Caroline Rouaux, Ph.D, Inserm U1118 – University of Strasbourg – France
Amyotrophic lateral sclerosis (ALS) is the third most frequent neurodegenerative disease after Alzheimer’s and Parkinson’s diseases, and the most frequent disease of the adult motoneuron. Clinically and histopathologically, ALS is defined as the simultaneous degeneration of corticospinal neurons (CSN) in the motor cortex, and bulbar and spinal motor neurons (MN), leading to muscle denervation, rapidly progressing paralysis and death. While preclinical studies have greatly contributed to our understanding of the mechanisms that govern MN degeneration, little is known about the contribution of the motor cortex, the CSN and other populations of cortical neurons and glia to MN survival and more broadly to disease onset and progression.** Recent clinical and pathological studies suggest that ALS might start in the motor cortex and spread along the corticofugal axonal projections (including the CSN), according to the so-called corticofugal hypothesis of ALS. Two mechanisms have been proposed i) altered cortical excitability and subsequent excitotoxicity, or ii) prion-like propagation of misfolded proteins. Using various mouse models of the disease and combination of behavioural, functional and molecular approaches, we are testing the corticofugal hypothesis of ALS in order to identify i) the type and kinetics of cortical impairments, ii) the contribution of corticofual populations to disease onset and progression, and iii) the type of detrimental message conveyed by the motor cortex to its targets. The long term goal of this research project is to determine whether the motor cortex and its cellular populations could represent new therapeutic targets and design innovative treatment strategies to combat ALS.
Friday 25 September 2020 à 11h30, Salle de conférence.
Potential roles of the kinase DCLK3 in neurons: from diseases to basic research
Emmanuel BROUILLET, Neurodegenerative Diseases Lab, CNRS/CEA, Fontenay aux Roses
I shall focus on new findings on DCLK3 (Doublecortin-like kinase 3), a kinase preferentially expressed in neurons, especially in the striatum and hippocampus. Our interest in this kinase came from a large scale transcriptomic analysis of the molecular signatures of neurons from different brain regions. We showed a possible role of DCLK3 in Huntington’s disease which is characterized by an early degeneration of the striatum and more recently discovered that this kinase in hippocampal neurons may play a role in spatial memory. Preliminary evidence that the function of DCLK3 may involve epigenetic mechanisms will be also presented.
Thursday 24 September 2020 à 13h, Amphi Lavoisier A.
Control of presynaptic function and excitability by endocytosis and the autophagy-endosomal system
Volker Haucke, Berlin, Germany
Wednesday 11 March 2020 à 11h, Salle de conférence.
Electrophysiological correlates of audio-visual conflicts
Sébastien Scannella, Institut Supérieur de l’Aéronautique et de l’Espace, Toulouse,France
The human cognitive system receives environmental information through multiple sensory channels. Most of the time, the channels provide congruent content, the integration of which helps to build a unified perception of the world. Sometimes, the environment provides inconsistent stimuli that prevent from an efficient interpretation. These situations may induce a conflict associated with a behavioural cost and disastrous consequences such as an airplane accident. The research presented here focuses and one of its consequences: the insensitivity to auditory alarms sometimes observed in pilots. We investigated the electrophysiological correlates of this conflict from well controlled lab tasks to realistic airplane environment.
Monday 9 March 2020 à 11h, Salle de conférence.
Neuroeductation and transfer effects from music training to novel word learning
Mireille Besson, Laboratoire de Neurosciences Cognitive, CNRS & Aix-Marseille Université, Marseille, France
In France, as in many other countries, there is an on-going public debate on whether and how knowledge issued from neuroscience and cognitive neuroscience can be used to better understand cognitive development and to implement neuroscience-based education methods. In the first part of my talk, I will review and discuss the /pro /and /cons /of neuroeducation. In the second part, I will illustrate these issues by showing how knowledge in cognitive neuroscience, as well as in linguistics, musicology and psychology, can be used to study the influence of learning to play a music instrument 1) on novel word learning in children and in adults, and 2) on the development of cognitive functions in children from low socio-economic backgrounds. These different issues will hopefully generate a vivid discussion.
Monday 2 March 2020 à 11h, Salle de conférence.
Synaptic restoration by cAMP/PKA drives activity-dependent neuroprotection to motoneurons in Amyotrophic Lateral Sclerosis
Francesco ROSELLI (Neurozentrum der Universitat Ulm, Germany)
Wednesday 26 February 2020 à 11h, Salle de conférence.
How infants start learning the grammar of their native language
Judit Gervain, INCC UMR 8002, University of Paris, France
Learning a new language is a challenging task. Yet, very young infants master their native language(s) in just a few years with ease and without any explicit teaching. Learning the grammar has been argued to be a particularly difficult learning problem, as speech contains very few direct cues to the underlying grammatical structure of sentences. Decades of research in developmental psychology has tried to identify the mechanisms that allow infants to achieve this feat. This talk will focus on the earliest mechanisms of grammar learning. It will argue that prenatal speech experience, i.e. speech heard in the womb, already lays the foundations of grammar learning, which thus starts very early on. A series of behavioral and brain imaging studies with newborns and young infants will be presented establishing some of the main mechanisms of this early learning, specifically prosodic and frequency-based bootstrapping, as well as their underlying brain mechanisms.
Monday 24 February 2020 à 11h, Salle de conférence.
Modélisation et traitement ex-vivo des lésions d’ischémie-reperfusion d’un greffon pulmonaire porcin par nanoparticules d’adénosine-squalène
Jean Baptiste Ménager
Friday 14 February 2020 à 11h30, Salle de conférence.
Synapse formation in the developing CNS – learning lessons from the neuromuscular junction
Stephan Kröger, Ludwig-Maximilians-University, Munich Allemagne
Wednesday 12 February 2020 à 11h, Salle de conférence.
Decision making and motor control in larval zebrafish
Ruben Portugues, Max Planck Institute of Neurobiology, Martinsried, Germany
In order to succeed in a changing environment, animals need to take into account noisy and ambiguous stimuli and select appropriate behavior. Furthermore, animals need to modify their behavior when the outcome is unsuccessful. In this talk, I will present two projects from my lab, which works on larval zebrafish, which touch upon these topics of decision making and motor control.
Friday 7 February 2020 à 11h30, Salle de conférence.
Early-life adversity and its long-term influence on cerebral oligodendrocytes and myelination
Naguib Mechawar, McGill University, Canada
Early-life adversity can have devastating and lasting consequences on individuals, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet, the neurobiological processes underlying this increase in vulnerability remain poorly understood. I will present some of our recent work, conducted with well-characterized post-mortem brain samples, indicating that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a fundamental feature of cerebral connectivity.
Friday 24 January 2020 à 11h30, Salle de conférence.
Visualising time in the brain
Jennifer Coull, Aix-Marseille University – CNRS UMR7291, France
Functional neuroimaging techniques have consistently identified a network of regions, including Supplementary Motor Area, basal ganglia, and prefrontal cortex, that are activated when participants make judgements about the duration of currently unfolding events. But why should the perception of duration be represented in regions of the brain more traditionally involved in motor function? One possibility is that we learn about time through action in childhood, potentially explaining why it has come to be represented in motor circuits of the adult brain. Yet duration judgements are not the only way of measuring how accurately time is perceived. Being able to predict when relevant events are likely to occur allows us to orient attentional resources to the predicted moment in time, thereby optimising performance. Indeed, speeded response times to temporally predictable events may actually provide a more suitable method for studying timing in cognitively fragile populations. In contrast to duration judgement tasks, the performance benefits of temporal predictability consistently activate left inferior parietal cortex. These neuroanatomical differences in duration judgement versus temporal prediction paradigms reflect distinct functional mechanisms for processing time.
Monday 20 January 2020 à 11h, Salle de conférence.
Dissecting Cognitive Complexity in a Miniature Brain
Martin Giurfa, University of Toulouse, France
Honeybees possess miniature brains but exhibit a sophisticated behavioral repertoire. In the last decades, bees have emerged as useful models for the study of the neural bases of simple forms of associative learning based on their capacity to learn elemental, univocal links between olfactory or visual stimuli and appetitive sucrose reinforcement. Recent work has shown the robustness of such learning and of the memories derived from i. Moreover, experiments by our team uncovered unsuspected cognitive capabilities in these insects such as conceptual forms of learning and a sense of numerosity, which require an explanatory level beyond that of elemental learning. I will discuss some of these findings, focusing on capabilities such as attentional modulation, non-elemental pattern discrimination and concept learning, and discuss their mechanistic bases in an attempt to trace them down to specific circuitries and neuromodulatory processes in the insect brain. In doing this, I will highlight experimental challenges and suggest future directions for investigating the neurobiology of higher-order learning in insects, with the goal of uncovering basic neural architectures underlying cognitive processing.
Friday 17 January 2020 à 11h30, Salle de conférence.
Exosomes and lysosomes in amyloid metabolism
Guillaume van Niel, Institute of Psychiatry and Neurosciences of Paris, U-1266 INSERM
Tuesday 14 January 2020 à 11h15, Salle de conférence.
Neural dynamics of the primate attention network
Sabine Kastner, Princeton Neuroscience Institute, USA
The selection of information from our cluttered sensory environments is one of the most fundamental cognitive operations performed by the primate brain. In the visual domain, the selection process is thought to be mediated by a static spatial mechanism – a ‘spotlight’ that can be flexibly shifted around the visual scene. This spatial search mechanism has been associated with a large-scale network that consists of multiple nodes distributed across all major cortical lobes and includes also subcortical regions. To identify the specific functions of each network node and their functional interactions is a major goal for the field of cognitive neuroscience. In my lecture, I will give an overview on the neural basis of this fundamental cognitive function and discuss recently discovered rhythmic properties that set up alternating attention states.
Friday 20 December 2019 à 11h30, Salle de conférence.
Using all-optical electrophysiology to study neural circuits in vivo
Adam E. Cohen, Departments of Chemistry and Chemical Biology and Physics, Harvard University, USA
High-resolution voltage imaging in vivo has long been a dream of neuroscientists. Recent advances in voltage indicator proteins, optics, and software bring this dream closer to reality. This talk will describe tools for all-optical electrophysiology in behaving mice, and application to dissecting the function of cortical Layer 1 in the mouse somatosensory cortex.
Friday 13 December 2019 à 11h30, Salle de conférence.
The Role of Temporal Memory in Cerebellar Purkinje Cells for Motor Timing
Fredrik Johansson, Lund University, Sweden
The general consensus for learning and memory is that changes in synaptic strength via long-term potentiation (LTP) and long-term depression (LTD) are the primary mechanisms for the formation of memories. Here, I will make the case that cerebellar Purkinje cell responses during eyeblink conditioning paradigms reveal a previously unknown cell-intrinsic learning mechanism which significantly differs from both LTP/LTD and changes in membrane excitability. When the conditional (CS) and unconditional stimuli (US) are delivered directly to the Purkinje cell’s immediate pre-synaptic afferents, the parallel fibres and the climbing fibre, the cell learns to respond to the CS with a pause in its spontaneous firing that reflects the interval between the two temporally separated CS and US onsets. After training, the CS duration can be manipulated but the cell still responds with the duration, e.g. 200 ms, that it was previously trained to. The pause response has a delayed onset and adaptively timed maximum, offset and duration, determined by the previously experienced CS-US interval. The timing is not dependent on any network-generated time-varying input. This implies the existence of a timing mechanism and a memory substrate that encodes the duration of the CS-US interval inside the Purkinje cell itself. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Instead, the Purkinje cell appears to learn an adaptively delayed interruption of the cell’s spontaneous firing for a specific duration.
Monday 9 December 2019 à 11h, Salle de conférence.
Neocortical dynamics during sensory discrimination behavior
Fritjof Helmchen, Brain Research Institute, University of Zurich, Switzerland
Through the combination of in vivo optical imaging and chronic expression of genetically encoded calcium indicators it is now feasible to directly ‘watch’ neuronal population dynamics in the neocortex of awake, head-restrained mice during specific behaviors. Here, I will present results from calcium imaging experiments in mouse neocortex while the animals perform whisker-based or auditory sensory discrimination tasks. We used wide-field calcium imaging to resolve spatiotemporal activation patterns across large parts of the neocortex during individual trials. We also chronically monitored cortical dynamics over weeks and across task learning. We observed wide-spread, coordinated activation of multiple cortical areas, which correlated with various behavioral aspects such as whisking, body movements, and licking. In particular, we identified highly distinct patterns of persistent cortical activity during a short-term memory phase, which were contingent of the animal’s behavior (active versus passive). We also found that posterior parietal cortex (PPC) presumably acts as a routing hub, with distinct subdivisions being activated for tactile versus auditory discriminations. During learning we identified two salient phases framing the effective learning period, which in particular reorganized the signal flow through posterior association areas, including PPC. Our results contribute to the understanding of the principles of large-scale activation patterns supporting sensory discrimination and of how these patterns emerge during learning.
Friday 22 November 2019 à 11h30, Salle de conférence.
Dynamics of membrane tension, synaptic vesicle recycling, and modulation of fusion pores by the neuronal calcium sensor Synaptotagmin-1
Erdem Karatekin, Nanobiology Institute, Yale University, New Haven
Calcium-triggered release of neurotransmitters and hormones entails fusion of cargo-filled vesicles with the plasma membrane (exocytosis). Although key molecules involved in this process and their basic functions have been identified, how these components work together to achieve release well within a millisecond after stimulation is not understood. After fusion, plasma membrane area returns to its pre-release value via endocytosis over much slower time scales (0.1-10 seconds). Two key factors that regulate release and vesicle recycling are dynamics of the initial nanometer-sized fusion pore and membrane flows. During release, some fusion pores fluctuate in size, flicker open-closed multiple times, and either reseal or dilate. Pore resealing results in recovery of a nearly intact vesicle– a rapid mechanism for vesicle recycling. To monitor dynamics of single fusion pores, we fuse ~25 nanometer phospholipid bilayer discs (nanodiscs) with engineered cells expressing components of the neuronal fusion machinery on their surfaces. The nanodiscs are reconstituted with complementary fusion proteins. Fusion results in a nanometer-sized pore whose dynamics are monitored using cell-attached, voltage-clamp recordings of currents passing through the pore. The method allows probing single pores with sub-millisecond time resolution. I will present how molecular crowding and mechanical forces generated by Synaptotagmin-SNARE-membrane interactions lead to larger pores. Another crucial factor regulating synaptic transmission by neurons and hormone release by neuroendocrine cells is membrane tension. In neurons, endocytosis occurs some distance away from the active zone where release takes place. Because exocytosis and endocytosis locally decrease and increase membrane tension, respectively, sustained exo-endocytic activity would lead to membrane tension gradients. Such gradients relax by membrane flows, which are extremely slow in plasma membranes of non-neuronal cells, or non-terminal regions of neurons. Slow membrane flows could limit spatio-temporal coupling of exo- and endocytosis, but have never been probed in presynaptic terminals. We characterized membrane tension dynamics in presynaptic terminals by pulling thin membrane tethers from them. We find extremely facile membrane flows and tension equilibration at presynaptic plasma membranes, which appear to be tuned for rapid turnover of synaptic vesicles, thus playing a key role in neurotransmission.
Monday 18 November 2019 à 14h, Salle de conférence.
How infants learn about themselves and others
Sabine Hunnius, Radboud University, The Netherland
From early on, infants explore the world around them with great interest: They watch their own hands as they move through their visual field, pay close attention to the people around them, and take pleasure in interacting with adults in a playful manner. But how do infants first learn about their own bodies and actions? And how do they develop the ability to understand actions they observe in others? In this talk, I will present a series of behavioral and neuroscientific experiments that examine how infants build models that allow them to generate predictions about own and others’ actions. In particular, I will discuss how active action experience and observational experience provide infants with the necessary information to learn about themselves and others and gradually develop complex social-cognitive capabilities.
Monday 18 November 2019 à 11h, Salle de conférence.
Multisensory mechanisms of place cells and theta rhythm
Mayank R. Mehta, Physics & Astronomy, Neurology, Neurobiology, UCLA
The hippocampus is responsible for learning and spatial mapping. How does the hippocampus turn sensory stimuli into mental maps of space and how do they guide navigation? To address these questions, we have developed a noninvasive virtual reality system for rats where sensory and behavioral variables can be precisely manipulated. We measured neural responses from the cortico-hippocampal circuit while rats performed spatial tasks, such as the Virtual (Water) Maze navigation. We developed computational techniques to decipher the emergent neural dynamics. We also measured the membrane potential of individual dendritic branches in freely behaving rats for up to four days. The results provide surprising insights about place cells and dendritic computations. These have some wider implications too, some of which are described here: https://www.youtube.com/watch?v=o4Ey8JzTDB
Friday 15 November 2019 à 11h30, Salle de conférence.
Social interactions and word learning in deaf children with cochlear implants
Derek Houston, The Ohio State University College of Medicine, USA
Children learn words in social contexts in which they and their caregivers interact and create moments of joint attention. Parent-child interactions are complex and multimodal, and differences in children’s sensory experiences may impact the quantity and quality of joint attention events. We investigate this possibility by conducting detailed analyses of interactions between deaf children with cochlear implants and their hearing parents during free play sessions with novel objects that were assigned nonword labels. During the sessions, parents and children wear head-mounted cameras and eye trackers, which allows us to gain rich information about the frequency and qualities of parent-child interactions from first-person perspectives. We are also able to assess the coordination of parent novel-object labeling with moments of joint attention. Data have been collected also from dyads with normal-hearing children. I will report between-group similarities and differences in social interactions and word labeling behaviors and discuss the possible implications of our findings for understanding how early auditory experience affects parent-child interactions and word learning.
Tuesday 5 November 2019 à 11h, Salle des Thèses.
Conscious awareness as inference in a higher-order state space
Steve Flemming, University College London, UK
Humans have the ability to report the contents of their subjective experience – we can say to each other, “I am aware of /X/”. However, the decision processes that support reports about mental contents remain poorly understood. In this article I propose a computational framework that characterises awareness reports as metacognitive decisions (inference) about a generative model of perceptual content. This account is motivated from the perspective of how flexible hierarchical state spaces are built during learning and decision-making. Internal states supporting awareness reports, unlike those covarying with perceptual contents, are simple and abstract, varying along a one-dimensional continuum from absent to present. A critical feature of this architecture is that it is both higher-order and asymmetric: there is a vast number of possible states nested under “present”, but a much smaller number of possible states nested under “absent”. A critical prediction of this framework (in contrast to global workspace approaches) is that there should be higher-order, symmetric neural coding of both presence and absence. In my talk I will first demonstrate this in simulation, before presenting the results of a recent experiment in which we identify evidence for such symmetry in human frontopolar and temporoparietal cortex. I interpret these results as initial evidence in favour of the higher-order state space view.
Monday 4 November 2019 à 11h, Salle de conférence.
Perceptual priors explain acquisition of high-level skills and its failure – in the general population, autism and dyslexia
Merav Ahissar, Hebrew University of Jerusalem, Israel
Quick updating of predictions (sensory and motor plans) – within .5-~3 sec, based on recent information, is crucial for adequate sensory-motor actions (like driving) and for social skills (on-line interactions with people). By contrast, inferences based on long-term stimuli statistics allow the formation of complex categories allowing fluent use of language, and acquisition of expertise. Analyzing performance in serial pitch discrimination we find that individuals with autism have difficulties with the former, whereas individuals with dyslexia have difficulties with the latter (Lieder et al., Nature Neurosci, 2019). A similar pattern is found in sensorimotor synchronization, where individuals with autism are slow in error correction, and hence fail in synchronization to external beats. Finally, studying the underlying neural mechanisms, we find that dynamics of inference is mirrored in the dynamics of cortical adaptation processes.
Monday 7 October 2019 à 11h, Salle de conférence.
Spatial and temporal windows in the human visual pathways
Jonathan Winawer, New York University
A successful visual system extracts meaning from stimuli that are spread over space and time. To do so requires integrating and segregating features at multiple scales. In this talk I describe a method to measure how sites in visual cortex pool information across the spatial extent of the image (spatial windows) and across time (temporal windows). The method is applied to signals from functional magnetic resonance imaging (fMRI) and intracranial electrical recordings in patients. One set of studies reveals a compressive nonlinearity in spatial summation. This effect becomes increasingly more pronounced in higher visual areas. The compressive spatial summation we observe has implications for a wide range of visual computations, including tolerance for changes in the position and size of objects. A second set of studies examines temporal windows across the visual pathways. As with space, we find that temporal signals are combined subadditively, and that the subadditivity increases in higher visual areas. The response patterns we observe in both space and time are explained in terms of a model with a small number of simple, interpretable computations. The parallels in the responses to space and time suggest that for the two domains, cortex uses a similar processing strategy to achieve higher-level and increasingly invariant representations of the visual world.
Friday 4 October 2019 à 14h, Salle de réunion LPP.
Rhythms of perception and attention: a multimodal neuroimaging approach
Thursday 3 October 2019 à 14h, Salle de conférence.
Molecular bases of astrocyte functions at neurovascular interfaces
Martine Cohen-Salmon, University of Giessen, Germany
Astrocytes are the most abundant glial cells in the brain. Although the astrocyte characteristics vary from one region of the brain to another, they all have a large number of processes that ramify into branches and then secondary branchlets. Hence, protoplasmic astrocytes are large, bushy-shaped cells with diameters of ~40-60 μm and volumes of ~10^4 μm^3 . Each astrocyte covers a unique domain, and (in humans) contacts up to 2 million synapses. At the synaptic interface, perisynaptic astrocyte processes sense the extracellular interstitial fluid, take up neurotransmitters and ions, and release neuroactive factors. Astrocytes are also in contact with blood vessels; indeed, the latter are entirely sheathed in perivascular astrocyte processes. The astrocytes at this interface modulate the integrity and functions of the blood-brain barrier, immunity, cerebral blood flow, and interstitial fluid drainage. The mechanisms underlying the astrocyte synaptic and vascular influence are critically important. Indeed, dysregulation of the astrocyte functions and interplay with neurons and the vascular system contributes to the development and progression of most neurological diseases. In our recent studies, we showed that mRNA distribution and local translation specific events occur at perivascular and perisynaptic astrocyte interfaces. We proposed that these mechanisms may be crucial to regulate distal astrocyte perivascular and perisynaptic functions.
Monday 30 September 2019 à 11h, Salle de conférence.
Harnessing opioid receptor signaling to improve therapeutic potential
Laura M. Bohn, Professor of Molecular Medicine and Neuroscience, The Scripps Research Institute in Jupiter, FL, USA
When drugs bind to receptors, they coordinate a series of signaling events that lead to physiological responses. Opioid receptors are G protein-coupled receptors (GPCRs); in addition to coupling to G proteins, they can be regulated by many different cellular proteins. The interactions between receptors and their signaling partners can vary between neuronal populations and tissues throughout the body; therefore there may be an opportunity to maintain efficacy in pain pathways while avoiding other side effects associated with opioid pain management. We are developing compounds that selectively engage certain signaling pathways over others to directly test if we can improve mu opioid receptor (MOR)- mediated pain relief while avoiding certain side effects, such as opioid overdose. Studies will also be presented comparing these compounds to conventional opioids in studies of antinociceptive tolerance and biological adaptations that accompany prolonged administration.
Friday 27 September 2019 à 11h30, Salle de conférence.
Bridging Modeling and Experimental Neuroscience
Wednesday 25 September 2019 à 14h, Salle de conférence.
Relationship between visual-spatial processing of objects and motor development in infants
Gudrun Schwarzer, University of Giessen, Germany
It is essential that infants learn to understand the visual-spatial characteristics of objects in their environment. This enables them to recognize objects despite changes in the viewing angles, and to visually anticipate and grasp them at the right moment when they move. That in turn allows infants to interact safely with objects and perform successful actions with them in everyday life. In this talk, I will provide empirical evidence that infants’ development of visual-spatial abilities is deeply interwoven with their motor development. First, I will demonstrate that infants’ mental rotation ability of objects and their predictive visual-spatial ability are clearly linked to their locomotion and manual object exploration skills. Then, I will present experiments in which we investigated visual and visual-manual mediators through which locomotion and manual object exploration most likely bring about improvements in infants’ visual-spatial abilities. Finally, I will introduce studies that examined the implications of this close coupling of visual-spatial development with motor development for young children with motor or visual impairment.
Monday 23 September 2019 à 11h, Salle de conférence.
Targeting muscle and metabolic pathologies to develop new treatment strategies for spinal muscular atrophy
Melissa Bowerman, Keele University UK
Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by reduced levels of the survival motor neuron (SMN) protein and characterized by motoneuron and muscle loss. Patients with the severe form typically die before the age of two while children with milder forms live into adulthood with limited motor abilities. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have recently approved the first SMN replacement strategy and additional promising SMN-enhancing gene therapies and small molecules are currently being evaluated. However, emerging results from pre-clinical and clinical studies highlight the need for approaches that will also include SMN–independent and systemic strategies. We and others have demonstrated that SMA patients and animal models display various metabolic and muscle pathologies that contribute to disease manifestation and progression. Our overall aim is to identify novel SMN-independent therapeutic strategies that ameliorate metabolic and/or muscle perturbations and that can be used in combination with clinically relevant SMN gene therapies for the treatment of all SMA patients.
Friday 13 September 2019 à 11h3, Salle de conférence.
Functional organization of the mammalian tactile sensory system: a view from the periphery
David Ginty, Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, USA
The sense of touch is key to our experience of the world around us, but unraveling the neural pathways underpinning this key sense has been a challenge. Research in my laboratoryuses the mouse as a model system to addressthe development,organization,andfunctionofneural circuitsthat underlie the perception of touch andpain, in health and disease. In this lecture, I will describe the range of mouse genetic toolswehavegeneratedthatenableinterrogation ofthemajor physiologically distinctclassesoflow-threshold mechanosensoryneurons(LTMRs),which arethe primarycutaneoussensoryneuronsthat mediateour sense oftouch, as well as nociceptors, which detect painful stimuli. I will also describea complementary set of genetictools useful for studying spinal cordinterneuronand projectionneuronsubtypes.These somatosensorynervoussystem toolshave enabledvisualization, targeted/invitro/and/invivo/electrophysiological recordings and imaging,andfunctional manipulation ofLTMRs as well asdorsal hornandbrainstem LTMR circuit componentsthat underlie thesense oftouch. I will then present recent workaimed at defining a conceptualframeworkfor understandinghowensembles ofLTMR activitiesare integratedand processed in thespinal cord and brainstem, and new insights into the properties and brain targets of ascending spinal pathways that underlie discriminative and affective touch.
Friday 6 September 2019 à 11h30, Salle de conférence.
Traces of top-down modulations of sensory responses in the behaving primate
Nicholas Priebe, Department of Neuroscience, University of Texas, Austin, USA
Early sensory cortical areas receive a large number of feedback projections from higher cortical areas, yet the role of these connections in mediating behavior is not well understood. Such top-down signals could optimize cortical representations for task demands, yet these modulations are likely to be subtle in order to minimize the interference with sensory signals that are useful for multiple concurrent perceptual goals. Consistent with this possibility, top-down modulations are typically small or absent in single unit measurements in macaque V1. It is possible, however, that important top-down modulations are present at the subthreshold level. Indeed, previous (Vm) studies using voltage-sensitive dye imaging, which measures the pooled membrane potential over large populations of neurons, revealed robust top-down modulations in macaque V1 (Chen & Seidemann, 2012), but the effects of these modulations at the single neuron level are unknown. The goal of the current study was to use whole cell recording to measure, for the first time, the effects of top-down modulations at the level of single V1 neurons. Two macaque monkeys were required to report whether a small, low contrast Gabor target appeared at one of two possible locations by making a saccade toward the target location. At a random interval after the animal established fixation, it received a temporal cue 300 ms prior to target onset (tone + fixation point dimming). In a subset of the trials, no temporal cue was given and no visual target appeared. On those ‘blank’ trials the animal was required to maintain fixation. As expected, when the target appeared in V1 neuron’s receptive field, we observed clear contrast-dependent visual response. However, when we compared Vm in detection trials in which no target appeared in the receptive field to Vm in blank trials, we observed reliable depolarization that started shortly prior to stimulus onset. V1 neurons exhibited significant Vm depolarization in the interval between target onset and saccade initiation (Monkey T, mean depolarization =1.84 +/- 0.15 mV, N=11, monkey A, mean depolarization = 1.24 +/- 0.19, N=11). Of the 22 recorded neurons, 18 showed significant Vm depolarization. This small but reliable depolarization has a weak effect on the spiking activity of single neurons, but is likely to have a robust effect at the level of neural population due to the highly interconnected nature of cortical circuits. These results demonstrate that primary visual cortex is not a purely sensory area, but instead contextual information modulates visual responses in a way that is likely to improve performance in demanding perceptual tasks.
Monday 24 June 2019 à 11h, Salle de conférence
Inducible and deterministic forward programming of human pluripotent stem cells into somatic cell types. – The stem cell promise fulfilled?
Mark Kotter, University of Cambridge, UK
The discovery of human stem cells has fueled hopes and expectation of using human cells for drug discovery, research and cell therapy. However, during the past two decades, technical challenges have limited a broad adoption of human stem cells. Many conventional differentiation protocols are challenging, lack consistency, and are not scalable. Direct cell reprogramming is a novel synthetic biology paradigm that is revolutionising our understanding of cellular identity. An ever-increasing number of protocols mediating transitions between cellular states challenge traditional concepts of cell types. Reprogramming was thought to be restricted to and predetermined by conducive metastable states of cells. Our recent work challenges these preconceptions. By overcoming gene silencing phenomena in human pluripotent stem cells, it is possible to deterministically reprogram human iPSCs into different human cell types within time scales of less than a week. Large scale ‘omics studies provide a detailed insight into the molecular processes that govern these rapid and efficient cellular transitions. In conclusion, cellular reprogramming overcomes known bottlenecks of stem cell research and has the potential of providing reliable cells for research and large-scale applications.
Friday 21 June 2019 à 11h30, Salle de conférence
The emergence of selectivity in the mammalian neocortex
Nicholas Priebe (Professor, Department of Neuroscience, University of Texas, Austin, USA)
The question of how precise response selectivity emerges in the visual cortex has been marked by considerable controversy, ever since Hubel and Wiesel first described orientation selectivity. Today, there are essentially two opposing views of how selectivity arises. Feed-forward models, derived from Hubel and Wiesel’s original proposals, rely entirely on the properties and organization of thalamic, or feed-forward, inputs to cortical cells. Feed-back models require some form of lateral inhibition to refine response selectivity relative to the rather weak bias provided by thalamic inputs. This debate has in large part been driven by the paradox presented by two divergent lines of evidence. On the one hand, many cortical response properties, such as cross-orientation suppression, orientation, direction and temporal frequency selectivities, appear to require lateral inhibition. On the other hand, while lateral inhibition could potentially provide considerable computational power to neuronal circuits, several lines of evidence suggest that it may not sharpen selectivity in the cerebral cortex. In intracellular recordings from primary sensory cortical areas /in vivo/, synaptic activity often lacks the necessary properties to support lateral inhibition. Specifically, inhibitory inputs are most often tuned to the same stimuli as the excitatory inputs, and inhibition evoked by non-preferred stimuli is generally weak. Additionally, inactivation of the cortical circuit, including both excitatory and inhibitory components, does not degrade the selectivity of the remaining feed-forward synaptic inputs. I will present intracellular /in vivo/ recordings that suggest a model for cortical computation that does not rely on lateral inhibition. Instead, we can explain complex aspects of cortical responses parsimoniously from simple, well-characterized, nonlinear features of the feed-forward excitatory pathways, such as spike threshold, contrast saturation, and spike rectification, along with stimulus induced changes in background membrane potential fluctuations. These changes in the amplitude and frequency of membrane potential fluctuations alter the relationship between the average membrane potential and firing rate, and act as a gain control element that shapes cortical selectivity.
Monday 17 June 2019 à 11h, Salle de conférence.
Visual recognition memory: A view from V1
Mark Bear, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology
Daily exposure of a mouse to a phase reversing, full-field visual grating stimulus reliably triggers a dramatic form of synaptic plasticity in primary visual cortex (V1) that alters the behavioral response of the mouse to this stimulus. This plasticity reveals itself in several different ways depending on how it is assayed. As the initially novel stimulus becomes familiar: (1) visual evoked potentials (VEPs) recorded in layer 4 _grow_ via mechanisms shared with long-term synaptic potentiation (LTP), (2) activity in a network of parvalbumin-containing inhibitory interneurons _decreases_, changing the state of oscillations in the local field potential, and (3) evoked cellular responses revealed by calcium imaging of layer 4 principal neurons are _depressed_. Understanding how these puzzle pieces fit together promises to reveal the neurobiological substrate of a simple but crucial form of visual recognition memory, manifested behaviorally as long-term habituation to stimuli that portend neither reward nor punishment. In humans, habituation deficits are a common feature of neuropsychiatric disorders. Studying this phenomenon in mice carrying gene mutations linked to psychiatric disorders may reveal pathophysiology that points the way to novel therapeutic approaches
Friday 14 June 2019 à 11h30, Salle de conférence.
The circuit mechanics of neuronal variability
Brent Doiron, Department of Mathematics, University of Pittsburgh, USA
Neuronal responses are notoriously variable, with sizable trial-to-trial and dynamics fluctuations in spiking activity that are shared across large populations of neurons. Furthermore, the degree and population structure of this variability is malleable, depending on host of stimulus and cognitive factors. I will present modelling and theoretical work that uncovers how spatially extended cortical circuits with large excitation that is balanced by an opposing inhibition can capture low dimensional shared variability reported in many population recording studies. The spiking variability in our model is also easily quenched through a top-down signal to inhibitory neurons, matching experimental results in spatial attention discrimination task. Finally, we explore how our circuit based manipulation of neuronal variability affects information flow as it propagates across cortical areas
Friday 7 June 2019 à 11h30, Salle de conférence.
Genetic and optogenetic dissection of the central stress response and stress-linked psychiatric disorders
Alon Chen Max-Planck Institute of Psychiatry, Munich, Germany and Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
The biological response to stress is concerned with the maintenance of homeostasis in the presence of real or perceived challenges. This process requires numerous adaptive responses, involving changes in the central nervous and neuroendocrine systems. When a situation is perceived as stressful, the brain activates many neuronal circuits, linking centers involved in sensory, motor, autonomic, neuroendocrine, cognitive, and emotional functions in order to adapt to the demand. However, the details of the pathways by which the brain translates stressful stimuli into the final, integrated biological response are not completely understood. Nevertheless, it is clear that dysregulation of these physiological responses to stress can have severe psychological and physiological consequences, and there is substantial evidence to suggest that inappropriate regulation, disproportional intensity, or chronic and/or irreversible activation of the stress response is linked to the etiology and pathophysiology of anxiety, depression and metabolic-related disorders. Understanding the neurobiology of stress by focusing on the specific genes and brain circuits, which are associated with, or altered by, the stress response, will provide important insights into the brain mechanisms by which stress affects psychological and physiological disorders. The long-term goal of our research is to elucidate the pathways by which stress is perceived, processed, and transduced into neuroendocrine and behavioral responses. We are using integrated molecular (genetics and epigenetics), biochemical, physiological and behavioral methods, with focus on the generation of mutant mice models as an in vivo tool, to study the roles of specific stress-linked genes and brain circuits in coordinating the neuroendocrine, autonomic and behavioral responses to stressful challenges
Monday 3 June 2019 à 11h, Salle de conférence.
Who am I? Representing oneself, according to the Theory of Event Coding (TEC)
Bernhard Hommel (Leiden Institute for Brain and Cognition, The Netherlands)
This talk is asking the question how we represent ourselves, and it gives an embarrassingly simple answer: just like any other event. I motivate my claim by introducing the Theory of Event Coding (TEC), which claims that perception and action are not only based on shared (i.e., sensorimotor) representations but are in some sense one and the same thing, and describe recent extensions of this theory to include the representation of self and other individuals. These extensions make surprising predictions, of which some have been already tested successfully by using the joint Simon task and virtual reality techniques
Monday 27 May 2019 à 11h, Salle de conférence.
The neurobiology of perceptual and value based decisions: A memorable connection
Michael Shadlen (Columbia University, New York, USA)
We ought to make decisions by combining evidence with prior knowledge (e.g., base rates) and the anticipated value/cost of deciding correctly. If the evidence arrives sequentially, the decision may take time as we wait for the accumulated evidence to reach a criterion level, or for a sufficiently compelling sample (e.g., an extrema). Both strategies are examples of /sequential sampling with optional stopping/ (SSwOS). It is surprisingly difficult to differentiate these strategies based on behavioral data, but I will supply two examples in which nonhuman primates use an accumulate-to-threshold strategy to make decisions. These examples, drawn from perception and reasoning, have helped to elucidate the neural mechanisms of decision making, including speed-accuracy relationships. I will suggest that they implicate the involvement of associative memory. This insight could help resolve a much larger mystery. Many decisions are supported by just a few samples of evidence, supplied at once. Yet these decisions also exhibit speed-accuracy regularities consistent with SSwOS. Value-based decisions, such as a preference between two familiar items, are exemplary. Such decisions take more time and the preferences are less consistent when the choice is between items of similar value. This speed-consistency relationship—analogous to speed-accuracy—is also explained by SSwOS. But what constitutes the samples of evidence? And why are they processed sequentially? In other words, where does the time go? I will describe recent findings (collaboration with Daphna Shohamy lab) that suggests the sequential samples are formed though a constructive process of valuation that draws on episodic (hippocampal) memory.
Monday 20 May 2019 à 11h, Salle de conférence.
Mechanistic insights into GBA1-associated Parkinson’s disease: therapeutic implications
Dimitri Krainc, Northwestern University, Chicago, USA
There is an urgent need to identify effective neuroprotective therapies for synucleinopathies such as Parkinson’s disease (PD) and Diffuse Lewy Body Dementia (DLB). Recent emergence of genetic forms of PD has facilitated identification of potential targets for therapeutic development. One of the most promising and extensively studied targets has been lysosomal glucocerebrosidase (GCase) in patients with GBA1-linked PD and DLB. These patients exhibit loss of GCase activity in lysosomes which in turn results in downstream neuronal dysfunction. Therefore, chaperoning and/or direct activation of GCase in lysosomes has been postulated as viable therapeutic strategy. Several ongoing therapeutic efforts have focused on chemical chaperones to promote translocation of mutant GCase to the lysosome. We found that wild-type GCase activity is also reduced in sporadic and genetic forms of PD, suggesting that wild-type GCase could serve as promising therapeutic target in synucleinopathies. Therefore, we explored whether activation of wild-type GCase could enhance lysosomal function and rescue downstream pathological phenotypes in dopaminergic neurons from patients with sporadic and familial forms of PD. We identified GCase activator S-181, which was able to increase the activity of wild-type GCase, and partially ameliorated lipid substrate accumulation, lysosomal dysfunction and dopamine oxidation, in both /GBA1/-linked and non-/GBA1/-linked PD patient-derived dopaminergic neurons. Our work thus suggests that rescuing GCase activity is sufficient to improve lysosomal function and to reduce accumulation of toxic oxidized dopamine in midbrain neurons. In turn, decreased accumulation of oxidized dopamine resulted in diminished downstream pathogenic effects, including oxidation-mediated modifications of GCase which disrupt its enzymatic activity. We found that this vicious feedback cycle could be interrupted by targeting wild-type GCase with small molecule activators in human DA neurons. Moreover, our /in vivo/ analysis in mice revealed that S-181 could penetrate CNS and enhance wild-type GCase enzyme activity in brain tissue. In sum, these findings point to the relevance of therapeutically targeting GCase across multiple genetic and sporadic synucleinopathies.
Vendredi 17 mai 2019 à 11h30, Salle de conférence.
Toward the study of brain mechanisms underlying free behavior in laboratory settings
Eli Nelken (Hebrew University, Edmond J. Safra Campus, Jerusalem, Israel)
The links between brain activity and behavior are often studied using very constrained tasks involving simple binary choices. We wanted to operationalize the notion of the use of sensory (specifically auditory) information to drive behavior, and for that purpose we developed a setup (the RIFF – rat interactive fantasy facility) that allows us to implement general Markov decision processes (MDPs) with a large number of action choices (up to 12 different ports for accessing food and water) based on auditory cues. The use of MDPs makes it possible to apply reinforcement learning theory in order to calculate optimal policies. Rats can freely move in the RIFF, and brain activity is recorded using telemetry or neural loggers on the animal. I will describe the RIFF and the theory underlying it, and present preliminary results regarding (1) the behavior of rats in the RIFF and its correspondence with optimal policies as well as optimal policies under information constraints; (2) neural activity recorded in primary auditory cortex as well as in the auditory field within the insular cortex, and its dependence on behavioral state
Monday 13 May 2019 à 11h, Salle de conférence.
An algorithm identifying adenosine deaminase 2 (ADA2) as a novel lysosomal protein, and a model of the pathomechanism underlying the inborn auto-inflammatory disease DADA2
Ole Kristian Greiner-Tollersrud, UiT The Arctic University of Norway
Friday 10 May 2019 à 11h, Salle de conférence.
The ecology of collective behavior
Deborah M. Gordon, Stanford University, USA
Like many biological systems, an ant colony operates without central control. Each ant responds to its interactions with other ants nearby. In the aggregate, these stochastic, dynamical networks of interaction regulate colony behavior Ants are extremely diverse, and species differences in collective behavior reflect relations with diverse environments. A long-term study of desert seed-eating ants shows how colonies regulate foraging activity according to food availability and humidity, and how natural selection is shaping collective behavior in current drought conditions. In the tropical arboreal turtle ant, trail networks respond to the distribution and stability of resources. The algorithms that generate collective behavior have evolved feedback regimes that fit the dynamics of particular environments. Examples from ants provide a starting point for examining more generally the fit between the particular pattern of interaction that regulates collective behavior, and the environment in which it functions. There are interesting analogies with the diverse functions of neural systems.
Friday 26 April 2019 à 11h30, Salle de conférence.
The role of confidence in self-regulated decision making
Nicholas Yeung, Professor of Cognitive Neuroscience, University of Oxford, UK
People are capable of finely calibrated evaluations of their own decisions–they often know when they have made an error and express graded confidence judgments that validly predict their objective accuracy. I will present explorations of the cognitive and neural basis of these confidence judgements, and their role in regulating decision processes: Knowing which decisions to make, when to seek feedback or advice, and who to trust when asking for advice.
Thursday 18 April 2019 à 11h30, Salle de réunion LPP.
Circuit mechanisms underlying CA1 place cell representations
Christine Grienberger, Baylor College of Medicine in Houston, USA
A crucial function of the brain is to produce useful representations of the external world. The hippocampus contains neurons tuned to fire action potentials (APs) in particular spatial locations within an environment. Collectively, populations of these place cells encode abstract and concrete environmental features. Our results demonstrate that place cells are driven by a subset of inputs whose elevated synaptic weights provide excitation that exceeds a spatially uniform level of inhibition. A novel form of synaptic plasticity called behavioral timescale synaptic plasticity (BTSP) mediates this increase in synaptic weights. BTSP has several distinct characteristics, including that it depends on dendritic plateau potentials (plateaus) instead of APs. Using two-photon Ca^2+ imaging in mice exploring for the first time a novel linear track we show that plateaus and BTSP shape CA1 place cell representations. Taken together, these results point towards a fundamental role of BTSP in creating CA1 representations and, thus, identify plateaus as a key signal instructing CA1 neurons which features to encode.
Monday 15 April 2019 à 11h, Salle de conférence.
Implicit Social Cognition
Mahzarin Banaji, Professeur, Harvard University, USA
How deep are the bounds on human thinking and feeling and how do they shape social interactions and decisions?For the past 30 years, I have studied attitudes and beliefs that operate without conscious awareness or conscious control.In social contexts, the decisions that stem from such implicit mental processes can be at odds with consciously expressed preferences and beliefs including one’s own values.From this basic dissociation between implicit and explicit attitudes and beliefs we have explored all aspects of the nature of implicit social cognition:its universality and cultural variations, its developmental origins, neural underpinnings, and stability and malleability.I will provide an overview of this research program with special focus on the experiments that are currently underway in the lab
Monday 15 April 2019 à 11h, Amphi Giroud.
Neurobiological substrate of food addiction
Rafael Maldonado, University Pompeu Fabra, Barcelona, Spain
Monday 8 April 2019 à 11h, Salle de conférence.
Role of non-neuronal cells in the death of neuronal cells in ALS and neurodegeneration
Serge Przedborski, M.D., Ph.D., Departments of Neurology, Pathology, and Cell Biology, Columbia University, New York, USA
Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. During this lecture, an integrative, systems biology approach that combines proteomics and regulatory network analysis to elucidate ligand-mediated interactions between distinct cellular compartments, will be discussed. It will be shown how such an approach could help unraveling the non-cell autonomous basis of neurodegeneration by using an experimental model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs). Integrative analysis identified the interaction between astrocyte-released N-terminal fragments of amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred pathogenic role of APP and/or DR6 was confirmed in vitro in both human sporadic and mouse familial ALS models, and in transgenic mutSOD1 mice with DR6 knockdown in MNs. Importantly, the proposed methodology is not restricted to this biological context and could be generalized to a variety of other non-cell-autonomous communication mechanisms.
Friday 22 March 2019 à 11h, Amphi Polonovski.
Functional circuits involved in motor learning
Agnès Gruart, Division of Neurociences, Pablo de Olavide University, Seville, Spain
The complexity of brain functions can only be approached by a multidisciplinary and comparative approach. The availability of genetically manipulated mammals (mice and rats) and of sophisticated electrophysiological techniques, susceptible of being applied in behaving animals during the acquisition of new motor abilities, have largely facilitated this approach. Our group has studied for years the contribution of sensory, motor, premotor, hippocampal, and prefrontal circuits to non-associative, pavlovian, and instrumental learning paradigms. For this, we have recorded activity dependent changes in strength in cortical and subcortical synapses during the respective acquisition process. Recently we have concentrated our attention to the contribution of prefrontal circuits to the acquisition and storage of instrumental learning tasks, including cooperative learning and decision making in mice and rats. The main hypothesis of our studies is that learning is the result of the activity of wide cortical and subcortical circuits activating functional properties of involved synaptic nodes. In particular, unitary firing, synaptic and local field potentials recorded in prefrontal sites are modified during the acquisition of the above-mentioned tasks. In addition, I will present recent evidences on the available information from our laboratory with respect to the use of these functional states for brain-machine interphase in behaving rats and for coordinated cooperation between pairs of rats aimed to achieve simultaneous rewards.
Friday 15 March 2019 à 11h, Amphi Polonovski.
Iris Berent, Professor, Northeastern University, USA
Why do we /tweet/ and /blog/, but not /wteet /and /lbog/? Every natural language forms words by patterning meaningless elements, and these patterns are strictly constrained. But the nature of these constraints is not fully understood. One possibility is that linguistic patterns are governed solely by sensory and motor restrictions—/lbog/ is avoided because it’s harder to hear and articulate. An alternative account asserts that linguistic restrictions are algebraic and abstract. Here, I revisit this debate from a novel perspective. In this talk, I ask whether phonological patterns in signed and spoken languages share common principles and computational mechanisms. Using the case of reduplication (XX, where X is a syllable), I first show that across modalities, phonological patterns rely on algebraic rules. Next, I demonstrate that people transfer their phonological knowledge across language modalities. Specifically, speakers with no command of a sign language spontaneously project the restrictions on reduplication from their native spoken language to linguistic signs. Finally, I explore the origins of these amodal restrictions in infancy.
Monday 11 March 2019 à 11h, Amphi Giroud.
Adaptive control of human reaching movements: a very fast neural mechanism for execution and learning
Frédéric Crèvecoeur, Université catholique de Louvain, Belgium
Classical studies in the field of motor learning have documented that humans and animals can learn to anticipate dynamical disturbances with practice, such as torque loads induced by the manipulation of a new tool. This important function of the nervous system supports adaptation to changing dynamics, yet the time scales at which this process influences behaviour has remained elusive. More precisely, it remains unknown how quickly motor adaptation alters movement control. Here we address this question in the context of human reaching movements performed in a virtual reality environment, and found that unexpected changes in the robot dynamics induced adaptation within a single movement. Furthermore, correlates of adapted control commands were found in surface recordings of motoneurons activity in about 200ms following reach onset. At this time, the online correction becomes tuned to the unexpected disturbance, which improved behaviour performances. We conclude that motor adaptation is supported at least in part by very fast neural mechanism that can adapt an ongoing movement and complement feedback control. These results highlight that feedback control and motor adaptation both participate in real-time adjustments of motor behaviour.
Monday 18 February 2019 à 11h, Salle de conférence.
Ticklishness, Ambivalence and Play
Michael Brecht, Bernstein Center for Computational Neuroscience, Berlin, Germany
In my talk I will describe neural and behavioral correlates of ticklishness and playfulness in rat somatosensory cortex. Rats greatly enjoy being tickled, as evident from approach behaviors, 50 kHz vocalizations and joy jumps (Freudensprünge). At the same time, rats fight the tickling hand, show escape behaviors and, under some circumstances, also emit 22 kHz alarm calls. Cells in the somatosensory cortex are involved in the generation 50 kHz vocalizations during tickling. Somatosensory cortical responses to tickling predict responses to play behaviors, suggesting a neural link between tickling and play. Finally, I will discuss behavioural and neural correlates of hide and seek in rats. The evidence suggests that rats have elaborate cognitive and neural capacities for role play.
Friday 15 February 2019 à 11h30, Salle de conférence.
Novel targets for mood disorders: exploring signaling pathway in mice and human
Eleni Tzavara, UMR 8002, Paris Descartes University, France
Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room of improvement, on their long delay of onset of action in particular. In this respect, novel compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience, are much warranted. The extracellular-signal-regulated-kinase (ERK) pathway is implicated in mood regulation, but its pleiotropic functions and lack of target specificity prohibit optimal drug development. Here, we identified the transcription factor Elk-1, an ERK downstream partner, as a specific signaling module in the pathophysiology and treatment of depression, which can be targeted independently of ERK. ELK1 mRNA was upregulated in postmortem hippocampal tissues from depressed suicides; in blood samples from depressed patients, failure to reduce ELK1 expression was associated with resistance to treatment. In mice, hippocampal Elk-1 overexpression per se produced depressive behaviors; conversely, the selective inhibition of Elk-1 activation prevented depression-like molecular, plasticity and behavioral states induced by stress. Our work stresses the importance of target selectivity for a successful signal transduction-based antidepressant approach, singles out Elk-1 as a depression-relevant transducer downstream of ERK and brings proof-of-concept evidence for its druggability.
Monday 11 February 2019 à 11h, Salle de conférence.
The Deep History of Counting Words
Mark Pagel, University of Reading, UK
English speakers use the counting word ‘/two’/, the French say /deux/, Greeks say δύο (/duo/), Russians say два (/dva/), Sanskrit speakers say /dve/, and Caesar would have said /duo/.English, French, Greek, Russian, Sanskrit and Latin are all members of the Indo-European family of languages. The various forms of the word /two/ that all these languages use are cognate – that is, they descend from a common ancestral proto-Indo-European form spoken perhaps 6000 to 8000 years ago and reconstructed by linguists as /duoh/. By comparison, each of these languages uses a different and non-cognate form of the word /bird/.I present evidence to show that the remarkable conservation of the word ‘two’ in the Indo-European languages is repeated in other language families and is typical of the deep histories of the simple counting words (taken here as the words representing ‘one’ to ‘five’), but not of most other words. I reflect on several reasons for the conservation of counting words, including speculation about numerical abilities having a hard-wired neurological basis.
Friday 8 February 2019 à 11h, Salle de conférence.
The physiology of excitation in the medial habenula: the novel role of GluN3A-containing NMDA receptors
Marco Diana, UMR 8246, Pierre & Marie Curie University, France
Much is known about the central role of conventional GluN1/GluN2 subunit-containing NMDA receptors (NMDARs) in glutamatergic synaptic transmission during normal and pathological brain states. However, there exists also a largely underappreciated group of glycine-binding NMDAR subunits, GluN3A and GluN3B, which have been so far uniquely associated with synaptic maturation and plasticity at early developmental stages. During this seminar, I will show that, in contrast to all expectations, GluN3A forms a completely novel type of excitatory glycine-activated receptors in the neurons of a specific region of the adult brain, the epithalamic medial habenula (MHb). The MHb is an important information hub linking the forebrain to neuromodulator-releasing caudal areas, which participates to the expression of physiological responses to stress, anxiety and fearful stimuli, and more generally to the treatment of aversive information. During my talk, I will describe the localization, the properties and the possible functional role of this novel receptor in the MHb. In particular, consistently with the complete lack of an afferent glycinergic plexus in the MHb, I will identify glial cells as a possible physiological source of the glycine leading to receptor activation. Finally, I will illustrate how the reduction in GluN3A expression levels in the MHb via interference RNA methods disrupts the development of aversive states, thus directly involving this novel receptor type in known MHb-related phenotypes. Overall, our data demonstrate for the first time the functional expression of purely glycine-activated excitatory receptors in adult native neurons and propose a signaling mechanism between glial and neuronal cells potentially controlling aversive states through the medial habenular relay station.
Monday 4 February 2019 à 11h, Salle de conférence.
How neurotransmitters reduce our antiviral defense
Jean-Philippe Herbeuval, UMR 8601, Paris Descartes University, France
Neurons are not restricted to the brain but are also present in very large numbers in the gut, which also represents the reservoir of immune cells. Recent discoveries have demonstrated a close dialogue between the nervous and immune systems. Immune cells communicate by secreting molecules called cytokine. These include interferons, which are antiviral proteins secreted in response to viral or bacterial infection. Present in most vertebrates, interferons act as guardians of our immunity. We have been focusing on the effect of neurotransmitters when the antiviral response is triggered. We have discovered that serotonin and histamine are potent inhibitors of interferon production in response to influenza infection. We next identified the chemokine receptor CXCR4 as the receptor used by neurotransmitters to inhibit interferons. Our study highlights a novel mechanism at the cellular and molecular levels in neuronal and immunologic interactions.
Monday 28 January 2019 à 11h, Salle de conférence.
Making sense of time in the Human mind
Virginie van Wassenhove, CEA DRF/Joliot, INSERM, Université Paris-Sud, Université Paris-Saclay
While we are all experts in “experiencing time”, introspection provides us with very little intuition regarding the neural mechanisms supporting time perception and temporal cognition. In this talk, I will discuss the importance of clocking mechanisms for the biology of the mind, and how oscillations help reframing temporalities from the perspective of the brain itself (as generator-observer of events) in opposition to that of the external observer (as information reader). I will illustrate this point by focusing on the role of oscillatory activity in low-level temporal logistics of information processing, yielding temporal order and behavioral precision. Second, I will focus on the notion that conscious timing does not linearly map onto neural timing – i.e., temporalities are represented abstractly and intelligibly – and exemplify this with recent work focused on the generative nature of the psychological time arrow (mental time travel), and the ability to introspect about one’s self-generated timing productions (temporal metacognition).
Friday 18 January 2019 à 11h, Salle de conférence.
Speech processing with (and without) cortical oscillations
Anne-Lise Giraud, University of Geneva, Switzerland
Perception of connected speech relies on accurate syllabic segmentation and phonemic encoding. These processes are essential because they determine the building blocks that we can manipulate mentally to understand and produce speech. Segmentation and encoding might be underpinned by specific interactions between the acoustic rhythms of speech and coupled neural oscillations in the theta and low-gamma band. To address how neural oscillations interact with speech and intervene in phonological processing, we developed neurocomputational models involving theta and gamma oscillations. By comparing models with and without oscillations, we establish that recognition performance are generally better with oscillations. Based on these models we hypothesized that if low-gamma oscillations are disrupted or shifted in frequency speech perception would still be possible, but phonemic units within syllables would have an abnormal format, potentially causing difficulties to map idiosyncratic phonemic representations with universal ones, as those we are taught to become aware of when learning to read. A disruption of the auditory gamma oscillation could hence account for some aspects of the phonological deficit in dyslexia. Using MEG, and EEG combined with fMRI, and neurostimulation, we found that dyslexia is associated with a specific deficit in low-gamma activity in auditory cortex, and that this deficit alone accounts for several facets of the disorder. Recently, we further found that boosting 30Hz neural activity in left auditory cortex using transcranial alternative current stimulation selectively improves phonological performance and reading efficiency. Altogether these results attempt to establish a causal role of oscillatory processes in speech perception.
Friday 30 November 2018 à 11h30, Salle de conférence.
Neurodegeneration due to impaired cholesterol metabolism: Niemann-Pick Type C disease
Frank W. Pfrieger, Institut des Neurosciences Cellulaires et Intégratives CNRS UPR 3212, 67000 Strasbourg
At present, it is unknown how cells in the brain achieve cholesterol homeostasis. Based on our previous findings we hypothesized that astrocytes provide cholesterol to neurons. To test this idea, we are studying a rare and ultimately lethal lysosomal storage disorder, Niemann-Pick type C with severe neurologic symptoms. The disease is caused by defects in either of two proteins that mediated cooperatively the exit of LDL-derived cholesterol from the lysosome. We are studying the mechanisms of neurodegeneration in NPC and possible therapeutic approaches.
Thursday 29 November 2018 à 11h, Salle de conférence.
Key role of loss of corticostriatal mGluR2 in the pathophysiology of addiction
Rainer Spanagel PhD, University of Heidelberg, Germany
Neuroscience research produces too many false positive results for the clinical situation – why? I will discuss several issues related to power problems, data robustness and generalizability, tolerance development and placebo effects. I will then argue that DSM-based animal models are warranted and will provide a show case for alcohol addiction. I will discuss face, construct and predictive validity of a DSM-based animal model and will then show translational results in convergent support for a hyperglutamatergic state in the addicted brain. This state is most likely driven by a GluR2 deficit in corticostriatal projection neurons and I will show that by viral-mediated gene transfer and pharmacological rescue of prefrontal mGluR2 function drug craving and relapse is suppressed in addicted subjects.
Friday 23 November 2018 à 11h, Salle de conférence.
Imaging neural ensembles in flexible behavior
Takaki Komiyama, University of California San Diego, USA
With repetitive practice, animals develop novel and stereotyped movements over time, a process called motor skill learning. Motor skill learning is supported by circuit changes at multiple spatiotemporal scales. We investigate these changes by applying imaging techniques in head-fixed mice learning a motor skill. Over weeks of daily training, mice develop increasingly more stereotyped movements. With two-photon imaging in the primary motor cortex, we have identified profound changes in both microcircuit activity and synaptic structures. These studies have established that motor learning modifies the relationship between brain activity and associated movements. These activity changes coincided with cell type-specific changes in synaptic structures. I will discuss our latest results regarding the micro- and macro-scale reorganizations of cortical circuits during motor learning.
Friday 16 November 2018 à 11h30, Salle de conférence.
Fore and aft: the human visual pathway as a model for trans-synaptic (trans-neuronal) degeneration
Gordon Plant, Medical Eye Unit, St Thomas’ Hospital, London
In the mid-19^th Century the English scientist Augustus Waller studied distal (direct anterograde) axonal degeneration following damage to the hypoglossal nerve in animals. The technique was later used to map neuronal connections in the brain and consequently this specific consequence of focal damage to an axon acquired an eponym: “Wallerian” degeneration. Waller however also realized the significance of his finding in the study of neurological disease and the potential for remote effects of focal damage. Trans-synaptic (trans-neuronal) degeneration is more difficult to study because of the length of time required for the observed effects to occur. The visual pathway is a convenient system to study these classes of degeneration because the retinal ganglion cells can be directly observed in humans in life and the vast majority of their axons have a single synapse in the lateral geniculate nucleus with a neuron that projects to layer IV of striate cortex. John M van Buren (who later became a Miami Neurosurgeon) published in the 1960’s evidence for retrograde trans-synaptic degeneration in both primate and human histological studies. However, its occurrence in humans remained controversial because standard clinical methods of observing the inner retinal layers could not detect changes in lesions acquired after birth. A decade ago I suggested employing the technique of optical coherence tomography to study the retinal nerve fiber layer thickness in human cases of both congenital and acquired occipital damage retrograde trans-synaptic degeneration does occur. We also investigated the time course in both acute and chronic lesions. In the past 10 years there has been increasing interest in trans-synaptic degeneration in a variety of disorders including multiple sclerosis (MS). We have recently suggested that an inner retinal finding thought to be related to the pathology of MS may be a non-specific example of retrograde trans-synaptic degeneration affecting bipolar cells and that the abnormalities in the brain thought to be evidence for glaucoma being a more generalized neurodegenerative condition can be explained by retrograde trans-synaptic degeneration.
Friday 26 October 2018 à 11h, Salle de conférence.
Hidden constraints on the control of movement: the importance of internal joint stresses and strains in determining muscle activations.
Matthew C. Tresch, Biomedical Engineering & Physiology Northwestern University
One of the guiding principles of motor control is that it is riddled with redundancy at all levels of analysis. For example, at the level of muscle activations there are many more muscles than degrees of freedom that need to be controlled to achieve task goals. However, this focus on how muscles contribute to task performance ignores another important consequence of muscle activation: how muscles affect stresses and strains within joints. Muscle actions on internal joint structures can be invisible at the level of task performance but, if improperly regulated, might lead to joint pain or injury. Our recent work examines these issues in the context of the neural control of quadriceps muscles in rats during locomotion. We perform biomechanical studies to characterize the action of these muscles on internal joint structures and task performance. Using this information we then perform experiments to demonstrate that the nervous system chooses muscle activations in order to minimize stresses and strains within a joint. These results suggest a reconsideration of the variables that the nervous system accounts for when choosing muscle activations and highlight the importance of understanding the richness of muscle actions when interpreting neural control strategies.
Thursday 25 October 2018 à 14h, Salle H335.
Synaptic modulation of spontaneous action potential activity
Larry Trussell from the Oregon Health and Science University at Portland
Tuesday 23 October 2018 à 10h, Salle de conférence.
Mechanisms of synapse maintenance and axon regeneration
Yishi Jin, University of California, San Diego, USA
Neural circuits established in embryonic development are often modified to meet dynamic needs in adult life. In /C. elegans, /locomotor circuit undergoes a dramatic connectivity switch in larval development. Operation of the adult locomotor circuit also requires balanced excitation and inhibition. We have employed integrated approaches starting from forward genetic screening to dissect intricate interactions in synapse formation, remodeling and maintenance. Additionally, the ability of neurons to respond to injury is vital for protecting circuit’s function. We have established an /in vivo /axon injury model to discover conserved genes functioning in axon regeneration. In this talk I will cover these two topics in neural circuit refinement and maintenance.
Friday 19 October 2018 à 11h30, Salle de conférence.
Interplay between protein aggregation and neuroinflammation in Parkinson disease
Seung-Jae Lee, Seoul National University College of Medicine
Synucleinopathies are neurological disorders, characterized by neuronal and glial deposition of a-synuclein aggregates. These disorders include Parkinson’s disease (PD), dementi with Lewy bodies, and multiple system atrophy. Cell-to-cell propagation of these aggregates are thought to be the underlying mechanism of aggregate spreading in patients’ brain and perhaps of clinical progression. Interfering with the aggregate propagation can thus be a potential strategy for halting the disease progression. However, the mechanism by which a-synuclein aggregates spread remains undefined. Here, I present the evidence that a-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous a-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase 1 depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of a-synuclein aggregates. Depletion of other genes such as ctsd (cathepsin D) resulted in lysosomal dysfunctions and further confirmed that lysosomal dysfunction is the key modulator of spreading of synucleinopathy. These studies define how a-synuclein aggregates spread among neuronal cells and explain how lysosomal dysfunction increase the risk of developing PD and other synucleinopathies. Another important issue regarding the aggregate propagation is the identification of receptors that mediate the propagation process. Recently, my lab identified toll-like receptor 2 (TLR2), an innate immune receptor, as the receptor for neuron-released a-synuclein oligomers in microglia. I will show evidence that TLR2 plays an important role in cell-to-cell propagation of a-synuclein aggregates, regulating both secretion and uptake of the aggregates. Furthermore, administration of a neutralizing antibody for TLR2 interferes with the intercellular propagation of a-synuclein and thus, alleviates synucleinopathy lesions and neuroinflammation. I propose the anti-TLR2 treatment as a therapeutic strategy for Parkinson’s disease and related synucleinopathies.
Friday 12 October 2018 à 11h30, Salle de conférence.
ORAI1, stromal interaction molecules 1/2, and ryanodine receptor type 1 shape sub-second Ca2+ microdomains upon T cell activation
Prof Andreas Guse from the University Medecine Hamburg Eppendorf
The earliest intracellular signals determined in T cell activation are local, sub-second Ca2+ microdomains (Wolf et al. 2015). Here we identify a Ca2+ entry component involved in Ca2+ microdomain formation in both non-stimulated and stimulated cells. In non-stimulated cells, spontaneous small Ca2+ microdomains depend on expression of ORAI1, STIM1, and STIM2. Using T cells stably transfected with ORAI1 fused to a genetically encoded Ca2+ indicator for optical imaging spontaneous Ca2+ microdomains depending on ORAI1 were also detected. Super resolution microscopy of non-stimulated T cells resulted in identification of a circular subplasmalemmal region with a diameter of approx. 300 nm with preformed patches of co-localized ORAI1, ryanodine receptors (RYR), and STIM1. Preformed complexes of STIM1 and ORAI1 in non-stimulated cells were confirmed by co-immunoprecipitation and Förster resonance energy transfer studies. Furthermore, within the first second of T cell receptor (TCR) stimulation, Ca2+ microdomain numbers increase in the subplasmalemmal space, an effect not observed upon genetic deletion of Orai1, Stim2 or Ryr1 or upon antagonism of the Ca2+ mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Taken together, while preformed clusters of STIM and ORAI1 allow for local Ca2+ entry events in non-stimulated cells, upon TCR activation, NAADP-evoked Ca2+ release via RYR1, in tight interplay with Ca2+ entry via ORAI1 and STIM, rapidly increases the number of Ca2+ microdomains, thereby initiating spread of Ca2+ signals deeper into the cytoplasm to promote full T cell activation.
Monday 8 October 2018 à 15h, Salle de conférence.
Becoming human: How (and how early) do language and cognition come together in the infant mind?
Sandra R. Waxman, Northwestern University, USA
Language is a signature of our species. To acquire a language, infants must identify which signals are part of their language and must discover how these signals are linked to the objects and events they encounter and to their core representations. For infants as young as 3 months of age, listening to human vocalizations promotes the formation of object categories, a core cognitive capacity. Moreover, this precocious link emerges from a broader template that initially encompasses vocalizations of human and non-human primates, but is rapidly tuned specifically to human vocalizations. This work showcases powerful contributions of both ‘nature’ and ‘nurture’ as infants discover increasingly precise links between language and cognition. I’ll discuss the impact of this early emerging language-cognition link for developmental cognitive and neurosciences.
Friday 28 September 2018 à 11h30, Salle de conférence.
ER-mitochondrial contact structure and calcium signalling.
Gyorgy HAJNOCZKY, from Philadelphia University and Thomas Jefferson University
The cell contains multiple types of organelles that need to function in a coordinated manner. Communication between organelles is mediated mostly by chemical signals. In the past, signals emitted by organelles were envisioned to spread throughout the cytoplasm to reach their targets. Recent evidence has shown, however, that organelles engage in physical coupling to form interfaces for specific, local communication. We propose that such interfaces may be considered a new class of organelles, ‘interface organelles’, in that they are physically separated from the larger cytoplasmic volume and contain specific types and concentrations of molecules to perform specialized functions. Indeed, many molecules and functions attributed to previously recognized organelles are segregated to the interfaces. We described such an interface organelle formed by the tethering of mitochondria, the powerhouses of the cell, to the source of cell building blocks, the endoplasmic reticulum (ER), and showed that the presence of this structure is critical for their communication (Csordas et al 2006 JCB, 2010 Molecular Cell). This mitochondria-ER interface has since been implicated in a range of disorders, including metabolic and neurodegenerative diseases and cancer. We have shown that the mitochondria-ER interface hosts calcium and reactive oxygen species nanodomains which provide for highly effective local signaling between the two organelles with broad impact on cell function (Csordas et al 2010 Molecular Cell, Booth et al 2016 Molecular Cell). In the present talk, we will discuss the mechanisms underlying calcium and reactive oxygen species local signaling and their relevance in signal transduction.
Wednesday 26 September 2018 à 11h, Salle de conférence.
Behavioral State-Dependent Role of Astroglia in Neuronal Circuit Activity
Dr. Martin Paukert (UT Health San Antonio)
Friday 14 September 2018 à 11h, salle Richet.
Aptamer as a therapeutic middle molecule
Pr. Yoshikazu Nakamura RIBOMIC Inc., Institute of Medical Science, The University of Tokyo
Friday 14 September 2018 à 11h, Salle des Thèses.
New Horizons in Research and Treatment of Diabetic Neuropathy
Eva L. Feldman, Department of Neurology, University of Michigan, USA
This talk will provide an overview of the anatomy of the peripheral nervous system and explain how injury to the peripheral nervous system leads to neuropathy. The discussion will then turn to a review of the global diabetes epidemic and how diabetes is the most common cause of neuropathy in the Western world. A review will then be presented of the clinical trials and our own preclinical research that informs us of the pathogenesis of diabetic neuropathy. The discussion will end with an example of how a clinical intervention, based on our research, provides a new treatment of diabetic neuropathy.
Friday 7 September 2018 à 11h30, Salle de conférence.
Somatic calcium imaging reveals simple spike activity of cerebellar Purkinje cells: applications and limitations to in vivo research
Wednesday 1 August 2018 à 13h, Salle de conférence.
Esquisse d’une théorie de la commande motrice basée sur les lois de la Mécanique
Christian Darlot, UMR INSERM 1093, Université de Bourgogne
Malgré le nombre d’études sur la motricité, la compréhension de l’organisation des voies motrice ne progresse que lentement. Une raison de cette lenteur est que les physiologistes ne considèrent pas les lois physiques du mouvement. L’hypothèse est donc faite qu’en partant d’une description physique du système moteur, et de quelques principes explicites de commande, il est possible de déduire la fonction de chaque partie des voies motrices : Cortex cérébral, Noyaux Gris Centraux, Cervelet, Noyau rouge… Une méthode de commande et de contrôle des mouvements dont l’efficacité soit mathématiquement prouvée et qui soit physiologiquement plausible a été proposée. Quatre hypothèses explicites supplémentaires sont posées : Hypothèse 1: Des signaux différentiels sont utilisés pour ajuster les ordres moteurs. Hypothèse 2: Le Cortex du Cervelet contient des modèles prédictifs de fonctions biomécaniques (très coûteux : des centaines de milliers de neurones). Hypothèse 3: Les signaux différentiels sont calculés par des neurones dans les Noyaux Cérébelleux (en l’occurrence dans le Fastigial). Hypothèse 4: Des calculs identiques ne sont pas faits deux fois dans le Système Nerveux. La validité de la méthode a été éprouvée sur l’exemple bien connu du système saccadique d’orientation de l’oeil. L’ensemble des contraintes biomécaniques et des lois de calcul postulées permet de tracer un circuit de commande dont la structure est comparable à la connectivité anatomique, et dont les signaux issus de chaque élément sont semblables aux activités neuronales enregistrées expérimentalement dans les régions correspondantes des voies neurales.
Monday 2 July 2018 à 14h, Salle de conférence.
Using automated controlled rearing to explore the origins of the mind
Justin Wood, University of Southern California
One of the great unsolved mysteries in science concerns the origins of the mind. While scientists have been interested in this topic for centuries, progress has been hampered by the lack of high-precision methods for studying newborn organisms. To overcome this barrier, my lab developed an automated controlled-rearing method for studying perceptual and cognitive development. Using automation, we can monitor newborn animals’ behavior continuously (24/7) within strictly controlled virtual environments. This approach allows us to study how mental abilities emerge in newborn animals, with an unprecedented degree of precision. In this talk, I will focus on the development of object perception. I will first describe studies showing that newborn chicks can build abstract object concepts rapidly, within the first days of life. I will then describe the experiential ingredients needed for the development of this ability. Specifically, newborn chicks need experience with natural visual environments, containing objects moving slowly and smoothly over time across patterned backgrounds. Without natural visual input, chicks develop abnormal or ‘incorrect’ object concepts. These results illuminate the role of experience in the development of object perception and provide high-precision benchmarks for testing computational models of newborn vision.
Friday 22 June 2018 à 11h30, Salle de conférence.
Molecular Plasmonics : Energy Transfer and Strong Coupling
Adi Salomon, Department of Chemistry, BINA nano-center, Bar-Ilan University
Thursday 21 June 2018 à 11h, Salle de réunion UMR8601.
How to write a paper…if you want it to be published!
Pr. Gary W. Miller, Emory University, Atlanta, USA
Wednesday 13 June 2018 à 11h, Salle de conférence.
Glial mismanagement of neuromuscular structure and function in ALS
Richard Robitaille, Montreal University
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with a complex etiology. The destruction of neuromuscular junctions (NMJs) is an early event that leads to muscle weakness and paralysis due to the denervation and retraction of nerve terminals from striated muscles. Despite the importance of NMJ denervation, NMJ vulnerability and resistance remain under-characterized and the mechanisms involved ill defined. We focus on the role of Perisynaptic Schwann Cells (PSCs), glial cells at this synapse, since they regulate NMJ synaptic transmission, morphological stability and repair. I will discuss ex vivo and in vivo experiments to illustrate that neuromuscular changes are precocious, with a strong influence of the local environment in the outcome of NMJ denervation in ALS. Data will be presented to suggest that targeting PSCs help restore NMJ innervation and muscle functions
Friday 8 June 2018 à 11h30, Salle de conférence.
DNA Bases beyond Watson and Crick
Pr. Thomas Carell, Faculty of Chemistry and Pharmacy, Munich, Germany
Friday 8 June 2018 à 11h, Salle de réunion UMR8601.
Centrifugal modulation of the olfactory bulb: the cocktail party effect for odors?
Diego Restrepo, University of Colorado Anschutz Medical Campus
Tuesday 5 June 2018 à 10h30, Salle de conférence.
Lipid Metabolism as a Therapeutic Target in Charcot-Marie-Tooth Disease 1A
Dr. Robert Fledrich, University of Leipzig, Germany
In patients with Charcot-Marie Tooth Disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. We could show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes the reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Importantly, the substitution of phospholipids in the diet is sufficient to overcome the myelination deficit of affected Schwann cellsin vivo, rendering lipid supplementation an easily translatable therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies
Monday 28 May 2018 à 11h, Salle des Thèses.
Using zebrafish embryos to dissect PrP-dependent, SFK-mediated and Abeta-induced neurotoxicity
Pr. Edward Malaga-Trillo – Université de Lima (Pérou)
Monday 28 May 2018 à 11h30, Salle du conseil.
Assembling neural circuits: cells and synapses
Joshua Sanes, Director of the Center for Brain Science, Harvard University, USA
The retina is a leading model system for elucidating mechanisms that govern neural circuit assembly and function. Visual information is passed from retinal photoreceptors to interneurons to retinal ganglion cells (RGCs) and then on to the rest of the brain. Each of >40 RGC types responds to specific visual features, depending on which of the >70 types of interneurons synapse on it. As an example, I will focus on RGCs that respond selectively to motion in a single direction, summarizing genetic, morphological and physiological studies that have led to identification of some mechanisms that underlie assembly of the circuit that generates their direction-selectivity. I will then discuss single-cell transcriptomic methods we are using to comprehensively identify cell types and candidate recognition molecules in both rodent and primate retina.
Friday 25 May 2018 à 11h30, Salle de conférence.
Schwann cell Neuregulin-1 in Peripheral Nerve Diseases
Dr. Ruth M. Stassart, University of Leipzig, Germany
In acute and chronic peripheral nerve injury, Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor. We could show that a transient glial NRG1 expression supports remyelination and functional recovery after experimental nerve crush in mice. In stark contrast, however, wo found chronic NRG1 signaling to elicit a vicious cycle of a repair response in a mouse model for the most common inherited neuropathy, Charcot-Marie-Tooth Disease 1A (CMT1A). Genetic disruption of NRG1 signaling in Schwann cells of CMT1A mice suppresses the hallmarks of progressive CMT1A disease, including hypermyelination and the formation of onion bulbs. Together, we suggest that diseased Schwann cells mount a common regeneration program that had evolved to overcome acute nerve injury, but turns into a detrimental overstimulation of Schwann cells in chronic neuropathies such as CMT1A.
Wednesday 23 May 2018 à 11h30, Salle de conférence.
Generating behavior without neural representation of the body – the special case of the soft-bodied octopus
Binyamin Hochner, Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel
Octopuses provide an outstanding example of successful motor behavior created with a flexible body lacking any form of skeletal support. In skeletal animals the interfacing of sensory and motor information for planning motor reactions is based on neural representation of sensory and motor information in body-part coordinates. In contrast, in hyperedundant soft-bodied animals this approach is impractical due to the infinitely large DOF needed to represent the soft body. Octopus evolution overcame this difficulty through coevolution of body and brain to fit the octopus’s highly active interaction with its environment. I will show that this was achieved thorough the selection of unique solutions at all levels, from the neuromuscular system of the arms up to the organization of higher motor control centers in the brain. All these unique solutions help explain how the “alien” or strange looking body of the octopus simplifies locomotion control; how the special distribution of the central and peripheral nervous system simplifies control of goal-directed arm movements like reaching and fetching; why higher control centers in the brain are not organized somatotopically as in vertebrates; whyarm coordination in locomotion involves probabilistic control mechanisms rather than a deterministic CPG;and, finally, why motor learning employs ‘strategy-learning’ rather than ‘skill-learning’. In summary, we learn from the octopus that embodied organization, a concept developed in robotics, is also an important biological principle for achieving simple and efficient neural control of behavior emerging from the adaption of the body’s physical properties and morphology to the behavioral task environment.
Friday 18 May 2018 à 11h30, Salle de conférence.
PPAR γ et développement placentaire: de la physiologie à la pathologie
Thierry Fournier, Faculté de Pharmacie de Paris, SPC, Paris
Thursday 17 May 2018 à 11h, Salle de conférence.
Parkinson’s disease: environmental clues and transporter blues
Pr Gary Miller (Emory University, Atlanta, USA)
Wednesday 18 April 2018 à 14h, Salle de conférence.
The short end and the long end of storing a motor skill.
Joseph Classen, Pr., University of Leipzig, Germany
Focusing on evidence using brain stimulation techniques, Joseph Classen will review how motor skills are acquired and stored over time. Motor training, resulting in immediate performance gains, and consolidation, the process of rendering motor skills resistant against perturbation can be differently affected by age and differently modulated by brain stimulation techniques. Motor synergies may constitute structures allowing for the efficient generation of flexible movements. They may also be viewed as devices for the storage of skills acquired over long periods (years) of training. Recent evidence suggests that motor synergies are formed bottom up, by the practice of movements, According to this idea, synapses whose activity constitutes the common building instruction of a movement repertoire may survive a “Darwinian” process allowing transition to late-phase potentiation. As the functional architecture of motor skill acquisition begins to unfold, the challenge will be to translate the knowledge into novel therapeutic strategies for treatment of neurological patients.
Friday 13 April 2018 à 11h30, Salle de conférence.
Quadruplexes are everywhere!
Jean-Louis Mergny, Institut Européen de Chimie et Biologie (IECB), Pessac, France
Thursday 12 April 2018 à 11h, Salle de conférence.
THE INVOLVEMENT OF AHR IN PERIPHERAL MYELINATION AND NERVE SHEATH TUMORIGENESIS
Tuesday 10 April 2018 à 9h30, Salle des Thèses.
Sex, brain and gender: From dimorphism to mosaic
Prof. Daphna Joel, School of Psychological Sciences and Sagol School of Neuroscience, Tel-Aviv University
Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). Studies in animals, however, suggest that sex differences in the brain do not ‘add up’ to create two types of brains. Indeed, a recent analysis of volume, cortical thickness, diffusion anisotropy, or connectivity in over 1400 human brains from four datasets reveals that most brains are comprised of unique ‘mosaics’ of features, some more common in females compared to males, some more common in males compared to females, and some common in both females and males. A similar analysis of gender-related data (behaviors, personality characteristics, emotional and cognitive abilities, and attitudes) of over 5500 individuals reveales that humans possessing only feminine (i.e., more common in women than in men) or only masculine characteristics are extremely rare. Scientifically, these findings call for a shift in our conceptualization of the relations between sex and the brain, from dimorphism to mosaic. Socially, these findings question the meaning of sex/gender as a social category.
Friday 6 April 2018 à 11h30, Salle de conférence.
Neural encoding of complex space
Kate Jeffery, University College London, UK
Studies of the hippocampal place system have previously mostly taken place in controlled laboratory environments in which animals were confined to single enclosures having simple geometry. However, the natural world is much more complex: it has multiple compartments or no compartments at all; it has complex surface topography such as hills, valleys, crevices, cliffs etc; it can be very small (a burrow) or very large (the ocean), and many animals, including our marine ancestors, can move freely in all three dimensions. This talk will explore the computational challenges faced by encoding complex space, and describe some of the studies that have begun to explore how mammalian brains deal with this complexity
Friday 30 March 2018 à 11h30, Salle de conférence.
Dopamine neuron self stimulation as a model of drug addiction
Christian Lüscher, Département des Neurosciences Fondamentales & Service de neurologie, Université de Genève
We propose addiction model based on optogenetic dopamine neuron self-stimulation (oDASS) of the ventral tegmental area (VTA). We show that oDASS leads to neural and behavioral adaptations typically observed after prolonged drug exposure, including compulsive self-stimulation despite negative consequences. We demonstrate the power of oDASS to investigate molecular and cellular alterations in identified neurons of a disease relevant neural circuit with the goal to reveal the mechanism underlying individual vulnerability to drugs
Friday 23 March 2018 à 11h30, Salle de conférence.
Prefrontal neuronal circuits controlling emotional behavior
Cyril Herry, INSERM U862, Université Bordeaux Segalen
When facing danger, mammals display a broad range of fear behavior ranging from active (avoidance) to passive (freezing) fear responses. The canonical model of fear circuits posits that the basolateral amygdala directly controls fear responses through projections to the brainstem. Using state of the art behavioral, electrophysiological and optogenetic manipulations we provide evidence challenging this view. Our results indicate that (i) specific cell populations within the medial prefrontal cortex support different coding strategy for fear behavior and (ii) that specific manipulation of prefrontal neurons projecting to the brainstem directly regulate conditioned fear responses
Monday 5 February 2018 à 11h, Salle de réunion LPP.
In vivo 3-photon Imaging of the Mouse Brain
Chris Xu, School of Applied and Engineering Physics, Cornell University
Over the last two decades, multiphoton microscopy has created a renaissance in the brain imaging community. It has changed how we visualize neurons by providing high-resolution, non-invasive imaging capability deep within intact brain tissue. Multiphoton imaging will likely play an essential role in understanding how the brain works at the level of neural circuits, which will provide a bridge between microscopic interactions at the neuronal level and the complex computations performed at larger scales. In this talk, the fundamental challenges of deep tissue, high-resolution optical imaging are discussed. New technologies for in vivo structural and functional imaging of mouse brain using long wavelength excitation and three-photon microscopy will be presented. We will discuss the requirements for imaging the dynamic neuronal activity at the cellular level over a large area and depth in awake and behaving animals, and identify the applications where 3-photon microscopy outperforms conventional 2-photon microscopy. We will speculate on the possible future directions to further improve the imaging depth and speed in scattering biological tissues.
Friday 19 January 2018 à 11h30, Amphi Lavoisier A.
Into the deep: cellular dissection of circuit function in cortical layer 6
Troy Margrie, University College London
Our laboratory applies electrophysiological, imaging and viral tracing methods to dissect the function of neuronal circuits in the intact brain. We are particularly interested in understanding the relationship between the intrinsic diversity, connectivity and in vivo function of individual cells and cortical circuits. Neocortical networks carry multiple functions and underlie higher-order sensory-motor processing, integration and decision-making. We currently focus on the most understudied layer of the cortex, Layer 6, which contains two classes of principal cells: cortico-cortical and cortico-thalamic projecting neurons. I will present data that suggests a functional distinction in visual processing between these two cell types. Furthermore, our connectivity data indicate a profound top-down input from retrosplenial cortex that signals the direction of head motion. Behavioural and theoretical experiments indicate that these inputs, distributed over a network of 100 L6 neurons, provide a reliable estimate and physiological separation of head velocity signals. We propose that this vestibulo-visual L6 circuit provides V1 with an internal reference signal used to frame and detect motion events occurring in the visual world.
Friday 12 January 2018 à 11h30, Salle de conférence.
Transformation of the head-direction signal into a spatial code
Adrien Peyrache, Montreal Neurological Institute and Hospital, McGill University
Animals integrate multiple sensory inputs to successfully navigate in their environments. Head direction (HD), boundary vector, grid and place cells in the entorhinal-hippocampal network form the brain’s navigational system that allows to identify the animal’s current location, but how the functions of these specialized neuron types are acquired remain to be understood. I will present how the internal dynamics of specialized brain circuits in the brain underlie the generation of a coherent and reliable HD signal. Then, I will show how the activity of HD neurons is influenced by the ambulatory constraints imposed upon the animal by the boundaries of the explored environment, leading to spurious spatial information. However, in the post-subiculum, the main cortical stage of HD signal processing, HD neurons convey true spatial information in the form of border modulated activity through the integration of additional sensory modalities relative to egocentric position, unlike their driving thalamic inputs. These findings demonstrate how the combination of HD and egocentric information can be transduced into a spatial code.
Friday 22 December 2017 à 10h30, Salle H352.
Simultaneous spatial representations in visual cortex and hippocampus
Julien Fournier, UCL
Animals rely on multiple navigational signals to estimate their own position in an environment. They can use vision to update their estimate based on visual landmarks. They can also perform path integration, i.e. estimate the distance they traveled from the previous location. Path integration and visual landmarks both contribute to the spatial representation in hippocampus. However, it is yet unclear whether navigational signals influence neural processing in sensory areas like the primary visual cortex (V1). We trained mice to lick in a specific position of a virtual reality corridor for water reward. On some trials, the gain of the virtual environment was changed so the animal had to run 20% more, or less, to reach the reward location, while visual landmarks remained at the same position along the corridor.While the mice performed the task, we recorded simultaneously from V1 and CA1 neurons. As expected, the activity of CA1 place cells depended on both visual cues and distance traveled. Surprisingly however, V1 neurons revealed a similar behavior: the position decoded from the V1 population was intermediate between predictions based on visual cues and distance traveled. Our results thus suggest a control of V1 activity by path integration. We propose that this control could rely on feedback position signals from the navigational system or on a direct influence of the distance traveled by integrating visual flow and self-motion signals.
Thursday 21 December 2017 à 14h, Salle H352.
Innovating with Technology-Enabled Blending Learning Experience (TEBLE)
Fun Man FUNG de la National University of Singapour
What inspires us to learn? How do we create an atmosphere of lifelong learning? How can we apply our creativity in our work as educators and inspire our students? In this seminar, Fun Man FUNG share his personal learning journey in making flipped classroom livelier, adopting educational technology to make instructional videos more realistic. From wearing the GoPro cameras and Google Glass to adopting the Lightboard, Fun Man has experimented with a number of filming devices that suits the blended learning model. He believes that this is one excellent way that excites our undergraduates, encourages them to learn better and cultivates intrinsic motivations, and that educators are in charge in ensuring students acquire a Technology-Enabled Blending Learning Experience (TEBLE) in the 21st century.
Thursday 21 December 2017 à 10h30, Salle du conseil.
Analysis-Characterization-Separation of Endotoxins in water by Capillary Electrophoresis
Fun Man FUNG de la National University of Singapour
This study focuses on one of the key environmental threats, endotoxins, also known as lipopolysaccharides (LPS). A capillary electrophoresis method in combination with laser induced fluorescence (LIF) detection was developed for the analysis of endotoxins from 16 different bacterial strains. LPSs were derivatized with the amino-reactive fluorescent dye, fluorescein isothiocyanate (FITC), separated by capillary zone electrophoresis (CZE) under the optimized conditions with the use of 50 mM sodium tetraborate buffer (pH 9.30), and detected by LIF detector. This CE method and SPE pretreatment showed linearity at 99.8 %, and repeatabilities at 8.4 % and 11 % for endotoxins from E. Coli O55:B5 and E. Coli O26:B6. The limit of detection (LOD) could reach around 5 ng/mL at optimized condition. The method was applied successfully to the determination of LPS levels in tap water and wastewater, and demonstrated sensitive, reproducible and reliable results.
Wednesday 20 December 2017 à 10h30, Salle du conseil.
Vesicular glutamate transport and regulation of glutamate release at the presynapse
Magalie MARTINEAU, Bordeaux
The refilling of synaptic vesicles with neurotransmitters is potentially a rate-limiting step in neurotransmission. Biochemical investigations on isolated synaptic vesicles had unraveled the basic properties of vesicular transporters and indicate that they all depend on a proton electrochemical gradient generated by the vacuolar-type H+-ATPase. Yet, the dynamics of vesicle refilling in intact neurons are still largely unknown. Therefore, I investigated the kinetics of vesicular reacidification in live cultured hippocampal neurons using pH-sensitive fluorescent reporters coupled to synaptic vesicle proteins. Using pharmacological inhibition of the vesicular glutamate transporters (VGLUTs) as well as Vglut1 knock-out (Vglut1-/-) mice, I identified VGLUT1 as a glutamate/proton exchanger associated with a thermodynamically-uncoupled chloride conductance generating most of the membrane potential used for glutamate uptake. In addition, I designed a vesicular ratiometric chloride indicator to monitor directly chloride dynamics. Using this sensor in neurons from wild-type and Vglut1-/- mice I was able to demonstrate the efflux of chloride through VGLUT1 during synaptic vesicle recycling, thus confirming its transport mechanism. Overall, my results provide important insights into the regulation of quantal size under physiological conditions. Finally, I will introduce the development of two red pH-sensitive fluorescent dyes coupled to antibodies against endogenous vesicular proteins. These dyes showed a higher response amplitude upon activity-dependent exocytosis compared to pHluorin. Their properties thus enable the detection of single vesicle fusion events and the investigation of the temporal and spatial organization of the synaptic vesicle cycle.
Tuesday 19 December 2017 à 10h30, Salle de conférence.
The neural basis of social behaviour in humans and non-human primates
Social skills require specific cognitive and emotional competences. Individuals with High Functioning Autism (HFA) cannot engage in social interactions despite preserved cognitive abilities. Recently, it has been suggested that oxytocin, a hormone known to promote affiliation and mother-infant bonds, may be implicated in the social deficit of HFA. We investigated the effects of intranasal oxytocin administration on the social behaviour of HFA patients and we found that after oxytocin inhalation, patients exhibited stronger social interactions and reported enhanced feelings of trust and preference. In order to understand the molecular events triggered by oxytocin in the brain we performed several experiments in humans and non-human primates by looking at the effects of oxytocin on 5-HT1A pathway. The results show that oxytocin increases serotonin neurotransmission.
Thursday 14 December 2017 à 11h30, Salle de conférence.
Neural mechanisms of memory re-evaluation: where did that memory go?
Scott Waddell Ph.D., University of Oxford
Animals must constantly reassess the reliability of the things they have learned so that their behaviour best reflects their most up-to-date knowledge. When experience suggests that a learned prediction is inaccurate the behaviour driven by the initial memory is reduced, by a process called extinction. Extinction is a conserved feature of memory in all animals but it is poorly understood. I will present mechanistic evidence from Drosophila that shows that when flies experience that an expected reward is missing they form a new aversive memory that competes with, and neutralizes, the initial food-seeking memory. In contrast, flies code omission of expected punishment as a good experience and form a competing reward memory. We propose that by retaining memories for the old and new experience, flies can more reliably track the likelihood of expected events.
Friday 8 December 2017 à 11h30, Salle de conférence.
Rethinking the role of machine learning in neuroscience
Konrad Koerding, University of Pennsylvania, Philadelphia, USA
The goal of much of computational biology is to numerically describe data from a system, but also to find ways of fixing it and to understand a system’s objectives, algorithms, and mechanisms. Here we will argue that, regardless the objective, machine learning should be a central contribution to progress in every flavor of biomedical science. Machine learning can typically better describe the data. In doing so it can also provide a benchmark for any other way of describing the data. Using examples from neuroscience we discuss how better performance matters for decoding models and how having a benchmark affects encoding models. Similar issues matter in medicine. As biomedical science evolves, machine learning is morphing into a critical tool across the full spectrum of scientific questions.
Friday 1 December 2017 à 11h30, Salle de conférence.
Mécanisme d’activation neuronale de mTORC1 et de son altération par le peptide amyloïde β
Wednesday 29 November 2017 à 14h30, Salle des Thèses.
Contributions du cervelet à l’apprentissage sensorimoteur : études anatomiques, fonctionnelles et comportementales des voies cerebello-thalamo-corticale et cerebello-thalamo-ganglions de la base chez l’oiseau chanteur
Tuesday 28 November 2017 à 14h, Amphi Giroud.
Implication du métabolisme du cholestérol dans la pathogenèse des amyotrophies spinales infantiles
Friday 24 November 2017 à 14h, Salle de conférence.
Transgenerational effects of early life trauma: Epigenetic mechanisms involving the germline
Isabelle Mansuy,University of Zürich, Switzerland
Behavior in mammals is strongly influenced by environmental factors, particularly when experienced during early postnatal life. While positive factors can favor proper behavioral responses, negative factors such as traumatic events can alter behavior and induce diseases like borderline personality disorder, bipolar depression and antisocial behaviors. Such disorders are usually marked in individuals directly exposed but strikingly, they can also affect their offspring sometimes across several generations. The biological mechanisms for the transmission of trauma-induced symptoms from parent to offspring have only started to be examined recently and are thought to involve non-genetic factors. This talk will present an experimental model of early traumatic stress in mice and will show evidence that non-genetic mechanisms are implicated in the expression and inheritance of the impact of such trauma. This mouse model exhibits altered social behaviors, depressive-like symptoms, cognitive deficits, and impaired glucose regulation in adulthood. The symptoms are pronounced and persist throughout life, but are also transmitted to the following offspring across several generations, through both females and males. They are associated with epigenetic alterations involving persistent changes in DNA methylation at the promoter-associated CpG island of several genes, in the brain of the offspring and the germline of their father. Further to DNA methylation, other non-genetic mechanisms involving regulation by non-coding RNAs and histone posttranslational modifications are also involved. These findings suggest that nongenetic processes largely contribute to the impact of negative environmental factors in early life on adult behavior, and its inheritance.
Friday 24 November 2017 à 11h30, Salle de conférence.
Régulation du complexe WAVE, une machine moléculaire essentielle à la migration cellulaire
Anna Polesskaya, UMR 7654, Ecole Polytechnique, Palaiseau
La polymérisation d’actine branchée par le complexe Arp2/3 fournit la force projetant la membrane plasmique lors de la migration cellulaire. Nous avons établi que le complexe Arp2/3 est régulé par un complexe activateur, le complexe WAVE, et une protéine inhibitrice, Arpin que nous avons récemment découverte. Dans les tumeurs les plus invasives de cancers du sein, il y a soit surexpression du complexe WAVE, soit perte d’expression d’Arpin. Ces altérations d’expression sont de mauvais pronostic pour l’apparition de métastases et la survie des patientes. Nous souhaitons maintenant comprendre comment la migration devient persistante. Pour cela, nous savons que des feedbacks positifs se mettent en place et qu’ils maintiennent la polymérisation de l’actine au front de la cellule. Nous avons trouvé par protéomique différentielle 6 partenaires du complexe WAVE dont l’association à WAVE dépend de la polymérisation d’actine. Nous sommes actuellement en train de cribler ces candidats pour identifier ceux qui régulent effectivement la persistance de migration, afin de comprendre les mécanismes de la formation des métastases.
Thursday 16 November 2017 à 11h, Salle de conférence.
Super-resolution microscopy by saturated speckle illumination
Super-resolution microscopy techniques recently broke the diffraction limit of optical microscopy, allowing to reach a detail of tens of nanometres in biological imaging. Unfortunately they are extremely hindered by aberrations. Therefore, this techniques can not be applied deep in opaque media, such as biological tissues. There, in fact, random diffraction scrambles light and generates speckle patterns, which make direct imaging impossible. Nevertheless, it has been shown that some information contained in speckle patterns can be extracted to « see objects hidden behind opaque layers » The aim of my work is to push this knowledge forward and prove that speckle patterns can also be used to perform super-resolution fluorescence microscopy. By saturation of fluorescence excitation and speckle patterned illumination, I give the proof-of-principle of super-resolution speckle imaging on fluorescent nano-beads and stained actin filaments. Finally, I demonstrate that this technique allows, for the first time, to perform 3D super-resolution imaging (in structured-illumination mode) with a simple 2D image acquisition.
Monday 30 October 2017 à 14h30, Salle de conférence.
Analysis of families for the identification of genes and mutations for multiple sclerosis
Pr Carles Vilariño-Güell, University of British Columbia
Wednesday 25 October 2017 à 11h, Salle de conférence.
Cerebellar contributions to coordinated locomotion in mice
Megan R. Carey, Champalimaud Neuroscience Program, Lisbon, Portugal
Smooth and efficient walking requires the coordination of movement across the entire body. In this talk I will describe our efforts to understand cerebellar contributions to locomotor coordination. We have developed an automated, markerless 3D tracking system (LocoMouse) to establish a quantitative framework for locomotion in freely walking mice. Analyzing the locomotor behavior of visibly ataxic mice with cerebellar defects has revealed specific, cerebellum-dependent features of locomotor coordination that suggest that cerebellar ataxia results from an inability to predict the consequences of movements across the body. In current experiments we are testing this idea by investigating neural circuit mechanisms of locomotor adaptation, in which mice learn to adapt their locomotor patterns to achieve a more symmetrical gait while walking on a split-belt treadmill. This approach is providing insight into how the highly stereotyped cellular architecture of the cerebellum supports a wide variety of behaviors, from relatively simple forms of learning to complex feats of coordination.
Friday 20 October 2017 à 11h30, Salle de conférence.
New optogenetic tools to visualize and control neural activity
Robert E. Campbell, Department of Chemistry, University of Alberta, Canada
Molecular engineering of improved fluorescent proteins (FPs) and innovative FP-based indicators has been a major driving force behind advances in cell biology and neuroscience for the past two decades. Among these tools, FP-based indicators (i.e., FP-containing proteins that change their fluorescence intensity or color in response to a biochemical change) have uniquely revolutionized the ability of biologists to visualize the otherwise invisible world of intracellular biochemistry. Similarly, light-activated protein-based actuators now enable researchers to control cellular activities with precise spatial and temporal resolution. In this seminar I will describe our most recent efforts to use protein engineering to make a new generation of versatile FP-based tools optimized for in vivo imaging and manipulation of cellular activity. Specifically, I will present our efforts to convert red and near-infrared FPs into indicators for calcium ion, membrane potential, and neurotransmitters, and describe our recent efforts to exploit FPs for optical control of protein activity and gene expression.
Friday 13 October 2017 à 11h30, Salle de conférence.
Hypothèse de la propagation de type prion dans les tauopathies: quelles conséquences thérapeutiques ?
Luc Buée, Equipe Alzheimer & Tautopathies, JPArc-UMR-S 1172, CHU- Lille
Thursday 12 October 2017 à 11h, Salle de conférence.
Le groupe III des récepteurs métabotropes du glutamate : une nouvelle cible dans l’addiction aux opiacés et à la cocaïne ?
Tuesday 26 September 2017 à 14h, Salle des Thèses.
Cellular and circuit mechanisms of spatial representations
Christoph Schmidt-Hieber, Pasteur
How are neuronal codes of the spatial environment generated at the level of synapses, neurons, and neuronal circuits? Neurons in the hippocampus and in the medial entorhinal cortex produce striking spatial firing patterns that may provide the brain with a cognitive map of the environment. In this talk I will show how we combine computational modeling, in vivo and in vitro recordings to understand how spatially modulated firing is generated at the synaptic, cellular and network level.
Tuesday 26 September 2017 à 10h30, Salle de conférence.
Le bioélectromagnétisme et l’étude des canaux TRPV à la lumière du BRET
Yann Percherencier, IMS / UMR 5218, Université de Bordeaux I
Friday 22 September 2017 à 11h, Salle de conférence.
Optogenetic modulation of gliotransmission
Friday 22 September 2017 à 14h, Salle de conférence.
Emerging medical technologies for interfacing the brain: CLINATEC brain computer interface project
Napoleon Torres-Martinez, CEA-Leti, GRENOBLE
Evolving medical technologies, including stimulators, infusion pumps, and neuroprosthesis, are addressing progressively a wide range of neurological conditions, bringing fresh hope to patients where other solutions have proven to be ineffective. In this context, brain-computer interfaces (BCIs), that allow interaction between neural tissue and an external device, have been developed for a many diverse conditions: in particular, they have allowed severely motor disabled patients to communicate and integrate better within their environment. Motor controlled-BCIs aim at providing users with control over upper or lower limb orthoses or prostheses. The major challenge for BCI systems with home use for motor disabled subjects is the ability of recording long term stable neuronal signals and decoding in real-time complex multi-limb effectors with robustness and precision. For 7 years we have been developing an ambitious program aiming at building an ECoG based BCI platform dedicated for a chronic clinical use. All these advances are however, limited by the mandatory long process of technological maturation and testing, for the benefit optimization and safety. Our institution has been developing new devices in these key areas, integrating medical teams and engineering expert from the device conception, addressing clear clinical problems from the early steps. New technologies are being made simpler and ever more close to reality and clinical trial than before; the design of innovative solutions to improve implantable devices opens a new era in clinical research.
Friday 22 September 2017 à 11h30, Amphi Giroud.
statistics on the number of released vesicles in a simple glutamatergic synapse
Thursday 21 September 2017 à 14h30, Salle de conférence.
CNS innate immune responses to flaviviruses impair learning and memory
Robyn S. Klein, MD, PhD, Washington University School of Medicine
Memory impairment following neuroinvasive infection with West Nile virus (WNV) is associated with inflammatory-mediated loss of hippocampal synapses with lack of recovery. WNV-recovered mice display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi of mice with poor spatial learning show increased expression of genes that drive synaptic remodeling by microglia, including the classical complement pathway and those that would limit adult neurogenesis, including interleukin (IL)-1, and increased markers of proinflammatory astrocytes. Adult neurogenesis and synaptogenesis are fundamental features of hippocampal restoration after injury, suggesting viruses might also impact these processes. This talk will provide an overview of flavivirus effects on neural cells with a focus on mechanisms of WNV-mediated impact on adult neurogenesis and synaptic repair.
Friday 8 September 2017 à 11h30, Salle de conférence.
The taste of infection
Wolfgang Kummer, Institute for Anatomy and Cell Biology, Aulweg 123, 35385 Giessen
A peculiar cell type of the respiratory and gastrointestinal epithelia, originally termed “brush cell” or “tuft cell” by electron microscopists because of its apical tuft of microvilli, utilizes the canonical bitter taste transduction cascade know from oropharyngeal taste buds to detect potential hazardous compounds, e.g. bacterial products. Upon stimulation, this cell initiates protective reflexes and local inflammatory responses through release of acetylcholine and chemokines. Guided by the understanding of these cells as sentinels, they have been newly discovered at previously unrecognized anatomical locations, including the auditory tube, the urethra, and the conjunctiva. Unexpectedly, they also have been identified in the epithelial network of the thymic medulla. The potential implications of the discovery of this novel cell type are enormous and far reaching, as these cells might be involved in monitoring and preventing ascending bacterial infection. However, although appealing, this is still speculative, since the actual number of distinct chemosensory cell types needs to be finally clarified, as well as their embryological origin, developmental dynamics, receptor equipment, modes of signalling to adjacent nerve fibres and other cells, repertoire of chemo- and cytokines, involvement in pathogenesis of diseases and many other aspects. The seminar talk will present yet unpublished data demonstrating direct responses to a novel class of bacterial products, paracrine cholinergic signalling, and dynamics of cell numbers and their role in bacterial infection.
Friday 30 June 2017 à 11h30, Salle de conférence.
Altérations des entrées synaptiques et origine de la vacuolisation dans les motoneurones SOD1-G93A, modele de la Sclérose Latérale Amyotrophique
Friday 30 June 2017 à , Amphi Giroud.
Three-dimensional Ca2+ imaging of astrocytes and astrocyte-synapse interactions
Andrea Volterra, University of Lausanne, Switzerland
Astrocyte communication is typically studied by two-dimensional Ca2+ imaging, but this method has not yielded conclusive data on the role of astrocytes in synaptic and vascular function. We developed a three-dimensional two-photon imaging approach and studied Ca2+ dynamics in entire astrocyte volumes, including during axon-astrocyte interactions. Results indicate that Ca2+ activity in an individual astrocyte is scattered throughout the cell, largely compartmented between regions, preponderantly local within regions, and heterogeneously distributed regionally and locally. Processes and end-feet display frequent fast activity, whereas the soma is infrequently active. Results also indicate that astrocytes respond locally to minimal axonal firing with time-correlated Ca2+ spots
Friday 23 June 2017 à 11h30, Salle de conférence.
Molecular Mechanisms of Oligodendrocyte Cell Identity: developmental and adult myelination
Patrizia Casaccia, Icahn School of Medicine at Mount Sinai, New York, USA
Myelinating oligodendrocytes derive from progenitor cells, whose ability to make myelin is dependent on the interplay between transcription and chromatin structure. The seminar will discuss nuclear changes underlying the acquisition of oligodendrocyte identity with an emphasis on histone modifications and DNA methylation. Because epigenetic changes reflect adaptation of cells to environmental stimuli, the effect of microscopic (i.e. mechanical forces) and macroscopic (including social experiences and fecal transplantation) changes in the environment will be presented.
Friday 16 June 2017 à 11h30, Salle de conférence.
Alcool, Polluants et Stress Hépatiques
Wednesday 14 June 2017 à 14h, Salle des Thèses.
Compartimentation structurale et fonctionnelle du neurone
Tuesday 13 June 2017 à 14h30, Salle des Thèses.
Imaging Pain, Analgesia and Anaesthesia induced altered states of Consciousness
Irene Tracey, Nuffield Department of Clinical Neurosciences, University of Oxford
The ability to experience pain is old and shared across species. Acute pain is the body’s alarm and warning system, and as such a good thing. Chronic pain is the system gone wrong and now one of the largest medical health problems worldwide. The brain is key to these experiences and relating specific neurophysiologic measures from advanced brain imaging to perceptual or non-perceptual changes in pain perception induced by peripheral or central sensitisation, psychological or pharmacological mechanisms has tremendous value. Identifying non-invasively where functional and structural plasticity, sensitisation and other amplification or attenuation processes occur along the pain neuraxis for an /individual/ and relating these neural mechanisms to specific pain experiences, measures of pain relief, persistence of pain states, degree of injury and the subject’s underlying genetics, has neuroscientific and potential diagnostic relevance. As such, advanced neuroimaging methods can powerfully aid */explanation /*of a subject’s multidimensional pain experience, analgesia and even what makes them vulnerable to developing chronic pain. Relatively far less work has been directed at understanding what changes in the brain occur during altered states of consciousness induced either endogenously (e.g. sleep) or exogenously (e.g. anaesthesia). However, that situation is changing rapidly. For example, our recent multimodal neuroimaging work explores how anaesthetic agents produce altered states of consciousness such that perceptual experiences of pain and awareness are degraded. This is bringing us fascinating insights into the complex phenomenon of anaesthesia. Learning Objectives: 1. The basic neuroanatomy of pain processing in the human brain – concept of a flexibly accessible network 2. How different neuroimaging techniques provide insight into chronic and acute pain (and analgesia) 3. How neuroimaging tools are being used to unravel how anaesthetics produce altered states of consciousness
Monday 12 June 2017 à 11h, Salle de conférence.
Localization of Synaptic Sites of Cortical Plasticity by MRI
Alan P. Koretsky, Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, MD
Functional MRI techniques have found widespread use to measure brain neural circuits that are used for a large number of behaviors. When circuit activity changes due to plasticity, it remains a challenge to identify sites of synaptic changes responsible for the circuit level changes measured.Of particular interest are the cases of long range cortical rearrangements that have been detected in the human brain after injury.Rodent models that mimic some of these cortical rearrangements have been developed and are being used to determine the synaptic basis for the plasticity detected. We have developed a model of adult cortical plasticity due to peripheral somatosensory nerve damage that is being used to develop MRI tools that can pinpoint sites of synaptic changes.Two weeks after peripheral denervation of one side of the forepaw, hindpaw, or whisker pathway there is a large up-regulation of cortical activity from the spared side and a large up-regulation of callosal inputs from the spared cortex to the cortical representation of the denervated area.A combination of functional MRI and laminar specific neural track tracing using manganese enhanced MRI predicted changes in thalamo-cortical inputs to layer IV that contribute to the up-regulation of cortical activity along the spared whisker barrel pathway. Slice electrophysiology confirmed that the thalamic inputs on layer IV stellate cells were strengthened by a post-synaptic mechanism.Interestingly this plasticity was caused by reopening of LTP using a silent synapse mechanism. Sites of plasticity that explain the up-regulation of the callosal communication have also been studied with MRI and slice electrophysiology.High temporal-spatial resolution fMRI demonstrates that up-regulation of the communication between the spared and denervated cortices likely occur through callosal inputs. These fMRI results were consistent with manganese enhanced MRI that predicts a strengthening of inputs into layer 2/3 and 5.Slice electrophysiology verified a large up regulation of callosal inputs into layer 5 pyramidal neurons.Taken together these results demonstrate that MRI is positioned to begin to give laminar specific information about mechanisms of cortical plasticity.
Friday 9 June 2017 à 11h30, Salle de conférence.
Entorhinal grid cells and spatial navigation
Francesca SARGOLINI, University Aix-Marseille, France
The discovery of the grid cells in the medial entorhinal cortex during the last decade represents a milestone in the comprehension of the neural systems involved in spatial navigation. Grid cells are spatially selective neurons whose firing fields form a regular hexagonal pattern across the 2D environment. This activity has been suggested to form an invariant selfmotion-based map that is relatively independent of the external landmarks. However, recent studies have strongly challenged this hypothesis by showing that in some conditions the grid map can be influenced by the external environment. In this conference I will present the results from these different studies as well as data from our lab showing that 1) the grid map strongly adapts to the topology of the explored environment, and 2) the hexagonal grid pattern is locally distorted around salient areas in the environment. Altogether these studies indicate that the entorhinal grid map is less invariant than previously thought, and strongly suggest that the external information (and not only the self-motion cues) is also primordial to establish the grid cell spatial activity
Friday 2 June 2017 à 11h30, Salle de conférence.
How does the action of spironolactone result in specific inhibition of HIV infection in T cells?
Dr. Cécilia Ramirez, Institut Cochin
We have recently shown that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4+ T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat-dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection (Lacombe *et al*, 2016). Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy. Present studies aim at elucidating how spironolactone inhibits Tat-dependent HIV transcription. In addition, SP also inhibited reactivation of latent HIV-1 proviruses in Jurkat-derived cells (JLAT) A1 and A2 that harbor a silent integrated HIV-1 mini-genome and JLAT 11.1 cells that harbor a complete HIV genome. No difference was observed when cells were cultured with or without EPL. Whether SP inhibits reactivation of viral production by CD4+ T cells from highly active antiretroviral therapy (HAART)-treated HIV-1-infected patients is currently under investigation.
Tuesday 30 May 2017 à 11h, Salle des Thèses.
GÉNÉTIQUE QUANTITATIVE DU METABOLOME
Marc-Emmanuel Dumas, Imperial College London
Wednesday 24 May 2017 à 10h30, Salle de conférence.
Probing neural circuits with shaped light
Na Ji (Janelia Research Campus, USA)
To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional relationships between individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter dimensions with sub-micron spatial resolution. I will describe how we use concepts in astronomy and optics to develop next-generation microscopy methods for imaging neural circuits at higher resolution, greater depth, and faster speed. By shaping the wavefront of the light, we have achieved synapse-level spatial resolution through the entire depth of primary visual cortex, optimized microendoscopes for imaging deeply buried nuclei, and developed a video-rate (30 Hz) volumetric imaging method. We apply these methods to understanding neural circuits, using the mouse primary visual cortex as our model system.
Friday 19 May 2017 à 11h30, Salle de conférence.
Precise spatiotemporal control the activity of native receptors in brain using photo switchable ligands
Friday 19 May 2017 à 10h30, Salle de réunion UMR8601.
The Memory Function of Sleep
Jan Born, University of Tübingen, 72076 Tübingen, Germany
Whereas memories are encoded and retrieved optimally when the brain is awake, the consolidation of memory requires an offline mode of processing as established optimally only during sleep. Recent studies have elucidated some of the neurophysiological mechanims underlying memory consolidation during sleep, especially in the hippocampus-dependent declarative memory system. This system is capable of rapidly forming an initial memory representation for an episode upon its one-time occurrence, and is thus at the basis of the formation of any long-term memory. Consolidation of hippocampus-dependent memories represents an active systems consolidation process that takes place mainly during slow wave sleep (SWS) rather than REM sleep. It critically relies on the neural reactivation of newly encoded memory representations which originates from hippocampal circuitry and stimulates the gradual redistribution of the representations towards extra-hippocampal, mainly neocortical networks serving as long-term store. The redistribution process goes along with a qualitative transformation of the representation ending up in the formation and storage of abstracted schema-like memories stored in the neocortex. Memory reactivations originating from the hippocampus, are synchronized to the <1Hz EEG slow oscillations that dominate SWS and are generated in neocortical networks, partly as a function of the prior use of these networks for encoding of information. By synchronizing hippocampocal memory reactivations with specific activity from other brain areas, including thalamo-cortical spindles, slow oscillations enable persisting plastic changes underlying the long-term storage of memories in the neocortex.
Friday 12 May 2017 à 11h30, Salle de conférence.
Optical techniques for fast clinical diagnosis
Ramon Alvarez Puebla
Friday 12 May 2017 à 11h, Salle de réunion UMR8601.
Cancer colorectal et alimentation : les défenses anti-oxydantes dans la balance?
Laurence Huc, UMR INRA 1331 ToxAlim, Toulouse, France
Thursday 11 May 2017 à 11h, Salle de conférence.
The Unexpected Role of Ligand Number in Specific Ion Binding
Susan Rempe, Sandia National Laboratories, Albuquerque, NM, USA
Tuesday 9 May 2017 à 11h, Salle de réunion UMR8601.
Rescuing deficits in neuronal plasticity after mild TBI
Barclay Morrison III, Columbia University, USA
Traumatic brain injury (TBI) continues to be a major socio-economic problem with about 2 million head injuries in the US annually, the majority being mild in severity.To understand better the mechanisms of TBI, we have developed in vitro models using organotypic brain slice cultures that afford precise control over injury biomechanics.With these models, we have previously developed tolerance criteria to determine safe levels of exposure that could be used to engineer better safety systems to prevent TBI.More recently, we have focused on how different mechanical stimuli (injury) may alter neuronal activity and electrophysiological function within hippocampal neuronal networks and explored therapeutic strategies to reverse pathological changes.Our recent findings suggest that after mild TBI, a disruption of dendritic organization may underlie deficits in long-term potentiation, i.e. the cellular correlates of learning and memory.We have identified therapeutic interventions that rescue LTP with therapeutic windows as long as 6 hours after injury.The long-term goal of our research is to reduce the socio-economic costs of TBI by developing novel treatments and by helping others engineer better protection systems.
Friday 28 April 2017 à 11h30, Salle de conférence.
présentation des travaux de doctorat financés dans le cadre du projet IDV
Imageries Du Vivant
Friday 21 April 2017 à 13h30, Salle de conférence.
A green chemistry approach
Estelle Metay, Laboratoire CAtalyse SYnthèse ENvironnement, ICBMS/UMR5246, Villeurbanne, France
Thursday 20 April 2017 à 11h, Salle de conférence.
Voie endosomale et Voie non-canonique d’autophagie : Comment le virus VIH-1 utilise ces machineries cellulaires pour contrer le facteur de restriction viral BST2/Tetherin
Clarisse Berlioz, Institut Cochin
La dissémination du Virus de l’Immunodéficience Humaine de type 1 (VIH-1) est un déterminant essentiel de la progression de la maladie vers le stade SIDA chez le sujet infecté. Pour contrer la propagation des virus, l’hôte a développé un arsenal de défenses immunes, dont des défenses cellulaires innées mettant en jeu des interactions entre protéines virales et protéines cellulaires. Parmi les composants de cette défense innée dirigée contre le VIH-1, on trouve les facteurs dit de « restriction », dont la protéine cellulaire BST2 pour « Bone marrow stromal antigen 2 », aussi nommée Tetherin. Ce facteur retient physiquement les nouveaux virus formés à la surface de la cellule productrice, réduisant *de facto* leur bourgeonnement et donc la production et la dissémination virale. Le groupe de Clarisse Berlioz-Torrent à l’Institut Cochin (U1016 Inserm, UMR 8104 CNRS, Université Paris Descartes Sorbonne Paris Cité) étudie comment le virus contre cette restriction virale. En effet, face à cette restriction, le virus a développé différentes stratégies pour diminuer le niveau d’expression de la protéine BST2/Tetherin présente au site de bourgeonnement viral et restaurer ainsi une production virale efficace. La protéine Vpu du VIH-1 est l’un des acteurs viraux capable de contrer cette barrière innée. En étudiant de plus près cette restriction virale, l’équipe de Clarisse Berlioz-Torrent a découvert que le virus VIH-1 *via* Vpu utilise la voie endosomale et une forme d’autophagie non canonique pour contrecarrer efficacement la restriction virale induite par BST2.
Wednesday 19 April 2017 à 11h, Salle de conférence.
Strategies for active sensation
Nicholas Priebe, University of Texas at Austin, USA
The Priebe laboratory is interested in mechanisms underlying response properties of neurons in primary sensory cortex using both electrophysiology and imaging /in vivo/. As sensory information moves from the periphery to the cortex the representation of the world is systematically transformed. Understanding the basis for these transformations sheds light on how the brain makes sense of the complicated world in which we reside.
Monday 3 April 2017 à 15h, Salle H335.
Brain energy metabolism assessed by genetically encoded sensors for metabolites
Johannes Hirrlinger, Carl-Ludwig-Institute for Physiology, Leipzig, Germany
To provide proper maintenance of brain function appropriate supply of energy is essential. Deficiency of energy delivery as e.g. during stroke or other injuries in the central nervous system will very quickly severely impair brain activity. Also during normal brain function, brain energy metabolism involves complex interactions of different types of brain cells. This metabolic cooperation between different types of brain cells has been a major topic of research in brain energy metabolism for many years focussing mainly on astrocytes and neurons for a long time and only recently also oligodendrocytes have entered the stage. To address the dynamics of metabolites within cells at an appropriate high spatial and temporal resolution we employed genetically encoded fluorescent sensors for metabolites like ATP, glucose, lactate as well as the NAD^+ /NADH-redox stateto follow the concentration of these metabolic parameters in real time in specific cell types both in vitro as well in tissue preparations. For example,using a novel transgenic mouse line expressing a sensor for ATP in neurons and an experimental setup allowing electrophysiology and confocal imaging of excised optic nerves simultaneously, we obtained novel insight into physiological but also pathophysiological axon-glia interactions in this well myelinated fiber tract. Furthermore, we now investigate the dynamics of several parameters of astrocyte metabolism. In summary, genetically encoded sensors for metabolites are powerful tools for an in depth analysis of metabolism and its regulation
Friday 31 March 2017 à 11h30, Salle de conférence.
Cognitive characteristics and neural basis of conscious perception in healthy adults, and clinical applications to non-communicating patients
My goal is to understand the psychological characteristics and the neural mechanisms of conscious perception. My project exploits two dynamic properties that I have contributed to reveal. First, the existence of a discontinuous jump in global cerebral activity during conscious access. Second, the discovery of the « retroperception » phenomenon, which shows that conscious access is flexible in time and is triggered by the reactivation of sensory areas by higher level areas. My project builds upon these discoveries in order to deepen our understanding of the mechanisms of conscious access in healthy adult volunteers, using experimental psychology, fMRI, MEG, EEG and intracranial recordings. The results of this fundamental research will also be the basis for constructing EEG tools for the diagnosis of consciousness in patients in a vegetative of minimally conscious state
Friday 31 March 2017 à 14h30, Salle de réunion LPP.
HIV-1 cell-to-cell transfer and dissemination to macrophages
Serge Benichou, institut Cochin
Macrophages are cellular targets of HIV-1 and participate in virus dissemination and establishment of persistent virus reservoirs in numerous host tissues. Recently, we revealed a very efficient mechanism involved in cell-to-cell transfer from infected T cells to macrophages and subsequent virus spreading between macrophages by a two-step cell fusion process. Infected T cells first establish tight contacts and fuse with macrophage targets. The newly formed lymphocyte/macrophage fused cells then acquire the ability to fuse with surrounding uninfected macrophages leading to the formation of infected multinucleated giant cells that could survive for a long time in host tissues as evidenced in vivo in lymphoid organs and the central nervous system of HIV-1-infected patients and SIV-infected macaques.
Tuesday 14 March 2017 à 11h, Salle des Thèses.
Seeing Colours, Feeling the Light: Probing the Visual and Non-visual Systems with Spectrally Tuneable Light
Anya Hurlbert (Newcastle University, UK)
Light shapes human behaviour, through both conscious perception and unconscious sensing of the environment. Variations in illumination spectra – the colour of light – are abundant in the natural and man-made worlds, and are important signals for both the visual and non-visual systems. The perceptual phenomenon of colour constancy – fundamental to colour perception and its role in object recognition – depends on the human visual system “discounting” spectral variations in illumination, so that we may recognise bananas as ripe yellow in twilight or bright sunshine, for example. The non-visual system monitors changes in light spectra to set biological rhythms and moods. Both systems originate in retinal light sensors – cones, rods, and intrinsically photosensitive retinal ganglion cells – whose spectral sensitivities and projection pathways partially overlap. Thus, the effects of spectral variations in light on the two systems interact. In this talk, I will describe a series of experiments which investigate these effects in humans, using spectrally tuneable light sources. We find, for example, that making lights “bluer”, for example, improves colour constancy, but leads to poorer performance on visual attention tasks and worse mood in the evening, despite increasing alertness.
Friday 10 March 2017 à 11h30, Salle de conférence.
Vers une compréhension des effets des petites molécules chimiques sur la santé humaine par l’utilisation d’approches de biologie systémique computationnelle
Karine Audouze, MTi, Université Paris Diderot, Paris, France
Thursday 9 March 2017 à 11h, Salle de conférence.
Cerebellum-dependent learning:an examination of memory consolidation processes and roles for the monoamine systems
Christopher Yeo (University College London, UK)
Simple forms of cerebellum-dependent motor learning, such as eyeblink conditioning (EBC), are good models to investigate how intelligent behaviour emerges from an identified neural network.Studies have shown that normal function within both cerebellar cortex and cerebellar nuclei is essential for the acquisition and expression of EBC learning but reversible inactivations of the cortical and nuclear control regions have revealed that consolidation and storage of this motor memory is essentially cortical.The findings are consistent with a recent model suggesting that the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent.There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in EBC, remains mainly dependent upon cortical memory storage. Electrophysiological studies have suggested a variety of candidate cerebellar neural plasticities that might underlie behavioural learning. Few, however, have analyzed the consolidation phase when the memories would normally be stabilized. New evidence now reveals that EBC consolidation can be disturbed profoundly by application of atenolol, a β1-adrenoceptor antagonist, to the cerebellar cortex, consistent with an early theory (Gilbert 1975) that cerebellar learning requires a noradrenaline signal for consolidation.Learning was significantly impaired in subjects that received infusions of the selective β1antagonist atenolol immediately after each of two training sessions but it was unimpaired in those that received atenolol infusions two hours post-training. Immunohistochemistry was used to map the distribution of β1 and β2-adrenoceptors and of noradrenergic afferents in the cerebellar cortex. A sharp dissociation of β1- and β2-adrenoceptors in the cerebellar cortex was seen. β1-adrenoceptor protein is entirely restricted to Purkinje cells whereas β2-adrenoceptor protein was almost completely restricted to Bergmann glia soma and processes, with very low levels in some Purkinje cells.In the cortical vermis, individual noradrenergic beaded afferents were seen to travel with limited medial-lateral extents (less than 250 microns) but with much longer rostro-caudal extents (up to 1mm and potentially longer), approximately consistent with the dimensions of individual cortical microzones. We conclude that noradrenaline provides an important consolidation signal for cerebellum-dependent learning in the two hours following training, that the noradrenergic afferents may target limited cortical territories and that the essential mechanism involves β1-adrenoceptors on Purkinje cells. That consolidation of amygdala-dependent fear memories and of hippocampus-dependent spatial memories are similarly sensitive to noradrenergic modulation strongly supports the suggestion that there is significant conservation of memory consolidation mechanisms across multiple brain regions.
Friday 3 March 2017 à 11h30, Salle de conférence.
Frequency dispersion in the cerebellar cortex
Stefan Hallermann, University Leipzig, Germany
First, I will recapitulate recently published findings regarding high-frequency signaling in the cerebellar cortex. Then, I will focus on the question how cerebellar granule cells (GCs) process the in coming signals: According to classical theories about cerebellar computation, each GC detects a specific pattern of active mossy fibers. Yet, mossy fibers convey broad-bandwidth neuronal signals ranging from several hertz up to kilohertz frequencies. How GCs detect this great diversity in the temporal patterns of the mossy fiber inputs remains unclear. We found that GCs closer to the white matter are gradually tuned to detect signals with higher frequency, and are less excitable than granule cells close to the Purkinje cell layer. The inner-zone GCs have parallel fibers that are tuned for high-speed signal propagation, project preferentially to the base of the Purkinje cell dendritic tree, and elicit faster postsynaptic potentials in the Purkinje cells. Implication for theories of cerebellar computation will be discussed.
Friday 24 February 2017 à 11h30, Salle de conférence.
Redox control of eukaryotic secretion by a new pathway regulating glutathione traffic in and out of the endoplasmic reticulum
Michel Toledano (CEA, Saclay)
Thursday 23 February 2017 à 11h, Salle de conférence.
Functional study of monoaminergic transmission
Bruno Giros (McGill University, Montreal, Canada)
Vesicular monoamine transporter (VMAT) allows vesicular uptake and accumulation of dopamine, serotonin and noradrenaline in the presynaptic compartment. We knock downed VMAT selectively in subpopulation of neurons to block neurotransmission and investigate dopamine and noradrenaline roles in degeneration of dopaminergic neurons and chronic stress, respectively.
Friday 3 February 2017 à 11h30, Salle de conférence.
Functional changes in neocortical neurons in a neurodegenerative disease, amyotrophic lateral sclerosis
Solange Brown (Johns Hopkins University, Baltimore, USA)
Neocortical hyperexcitability is a prominent feature of inherited and sporadic amyotrophic lateral sclerosis (ALS) and is inversely correlated with patient survival. Cell-type specific changes in neuronal function have been proposed to underlie these functional abnormalities and contribute to the selective degeneration of corticospinal and spinal motor neurons in ALS. Using a commonly used mouse model of ALS, we analyzed the functional properties of different classes of neurons in the motor cortex using electrophysiological recordings, in vivo calcium imaging and RNA sequencing of purified populations of neurons. We found widespread, stage-dependent alterations in neuronal function and circuit organization in ALS mice that highlight the dynamic changes cortical circuits experience during neurodegeneration and expand potential therapeutic strategies for normalizing circuit function.
Friday 27 January 2017 à 11h30, Salle de conférence.
Novel models of stretch-induced injury in mouse oligodendrocytes and organotypic culture of cerebellar slices: study of pathophysiological mechanisms
Friday 20 January 2017 à 14h, Salle de conférence.
Genetic and chemogenetic dissection of neuro-glio-vascular interactions in motoneuron disease
Francesco Roseli (Ph.D., Neurology and Anatomy Departments, University of Ulm, School of Medicine, Germany)
Amyotrophic lateral sclerosis (ALS) is recognized to display non-cell-autonomous pathogenetic cascades, in which motoneuron processes strongly affect, and are strongly influenced by, events taking place in astrocytes, microglia, vascular structures as well as other neurons. The mechanistic analysis of these interactions requires the precise spatio-temporal control of one or multiple components /in vivo/. By applying chemogenetic and genetic strategies, we are now able to manipulate each cellular player independently, establishing causal links and exploring pathogenic cascades in space and time.
Friday 13 January 2017 à 11h30, Salle de conférence.
De la perception des objets dans des environnements visuels dégradés à la mesure du couple perception-action dans des environnements intelligents
A travers la mesure du comportement, notamment dans ses composante de prise d’information perceptive visuelle et de son lien avec les actions des opérateurs, des sujets sains ou présentant des pathologies neurologiques, je travaille au sein de deux laboratoires à caractériser les conditions limites permettant de détecter et prédire des ruptures dans les processus nominaux de l’activité. Cette recherche est fortement ancrée dans une démarche multidisciplinaire, et ne peux aboutir sans le concours des camarades chercheurs en mathématiques appliquées, en traitement du signal et les cliniciens. Trois projets de recherche en cours concrétisent cette direction de recherche. L’appartement intelligent permet d’étudier les dimensions mesurables du comportement à l’hôpital et à domicile, et de détecter les indices de perte d’autonomie ou les modulations fines du comportement de patients, de même que des réponses à des thérapeutiques nouvelles. Cet aspect est également au cœur du projet multidisciplinaire pour l’autonomie que je coordonne. Je m’intéresse à la perception des objets en condition dégradée, comme en vision de nuit, avec ou sans aide optronique. Enfin, nous étudions dans des simulateurs d’hélicoptères les dimensions mesurables des modulations de la charge de travail des pilotes.
Wednesday 21 December 2016 à 14h, Salle de conférence.
From exploration to fixation: how eye movements determine what we see
Susana Martinez-Conde (State University of New York, USA)
Vision depends on motion: we see things either because they move or because our eyes do. What may be more surprising is that large and miniature eye motions help us examine the world in similar ways – largely at the same time. In this presentation, I will discuss recent research from my lab and others suggesting that exploration and gaze-fixation are not all that different processes in the brain. Our eyes scan visual scenes with a same general strategy whether the images are huge or tiny, or even when we try to fix our gaze. These findings indicate that exploration and fixation are not fundamentally different behaviors, but rather two ends of the same visual scanning continuum. They also imply that the same brain systems control our eye movements when we explore and when we fixate – an insight that may ultimately offer clues to understanding both normal oculomotor function in the healthy brain, and oculomotor dysfunction in neurological disease
Friday 9 December 2016 à 11h30, Salle de conférence.
Is it time for immunopsychiatry?
Marion Leboyer (Institut Mondor, Créteil, France)
Major psychiatric disorders such as schizophrenia, bipolar disorder, depression, autism are frequent ( affecting 30% of population in Europe). These disorders are the causes behind chronic pathologies which are debilitating for sufferers in addition to being an economic burden for society. This is major public health issue, and it is set to become the number one cause of disability around the world by 2020. Yet these disorders are still not well understood and often diagnosed late reflecting a lack of understanding of the etiological mechanisms at work and the absence of therapeutical innovations in this domain. However, paradigm shifts and new etio-pathogenic hypotheses should quickly help us to develop new diagnostic and therapeutical tools. Hypotheses around immuno-inflammatory dysfunctions offer a new understanding of physio-pathological pathways which could explain the complexity of these pathologies by placing them at the centre of interactions between triggering and inducing factors that occur throughout a person’s life. They also offer the possibility of new diagnostics and therapeutic approaches, paving the way for personalised care that is in line with other fields of medicine. I will explain how these different approaches all offer tools with which we can better understand, diagnose and treat mental illness.
Friday 2 December 2016 à 11h30, Salle de conférence.
Le compartiment axonal chez les interneurones de la couche moléculaire du cervelet: de la transmission du potentiel d’action à la libération du neurotransmetteur.
Friday 25 November 2016 à 14h, Amphi Giroud.
la connectivité GABAergique des précurseurs d’oligodendrocytes durant le développement cortical
Friday 25 November 2016 à 14h, Amphi Lavoisier A.
IMAGING THE BRAIN: lights vs. ultrasound vs. electromagnetic field
*Dr.* *David DiGregorio*, /Dynamic Neuronal Imaging Unit/, Pasteur Institute, Paris
*Dr. Mickael Tanter*, /Wave Physics for Medicine Lab/, Langevin Institute, ESPCI, Paris
*Darinka Trübutschek*, /Unicog, Neurospin, INSERM-CEA/, Saclay.
Thursday 24 November 2016 à 18h, Salle de conférence.
Des circuits hippocampiques non canoniques
Wednesday 9 November 2016 à 12h, Salle de conférence.
Understanding presynaptic function at nanometer resolution
Vitaly KLYACHKO, Washington University, Saint Louis
Tuesday 8 November 2016 à 11h, Salle de conférence.
The Chemical Biology of Epigenetic DNA and RNA base Modifications
Prof Thomas Carell, Ludwig-Maximillians University, Munich, Germany
Monday 7 November 2016 à 11h, Salle de conférence.
Etude mécanistique et physiologique du transporteur lysosomal d’acides aminés PQLC2
Monday 7 November 2016 à 14h, Salle des Thèses.
Putting sensory back into voluntary control
Stephen Scott (Queen’s University, Canada)
Optimal feedback control can explain many features of biological movement, such as success with variability, motor synergies and goal-directed behavior. The lecture will describe the use of optimal control to interpret motor performance, highlighting the importance of sensory feedback in this process. My talk will highlight how simple mechanical disturbances applied to the limb can uncover a range of sophisticated feedback processes, including knowledge of limb mechanics, scaling to spatial target location, avoidance of obstacles and selection of alternate goals. As well, I will highlight how sensory and motor cortices participate in this online control
Friday 4 November 2016 à 11h30, Salle de conférence.
On the Development of Transannular Mannich (TAM) Reactions for the Synthesis of Polycyclic Alkaloids
David Tanner (Department of Chemistry, Technical University of Denmark)
Thursday 20 October 2016 à 11h, Salle de conférence.
What good are dendritic spines – a voltage-imaging study
Dejan, Zecevic, Yale University (Dept C/M Physiology)
Wednesday 12 October 2016 à 11h, Salle de conférence.
Navigating the cytoskeleton: new tools to dissect and direct intracellular transport
Lukas Kapitein, Department of Biology, Utrecht University, Pays-Bas
Cellular organization depends on the cytoskeleton and the motor proteins that walk along cytoskeletal fibers to distribute cellular components. Nevertheless, the precise mechanisms that control cytoskeletal organization, the function and dynamics of different motor proteins, and the precise functions of subcellular positioning are still poorly understood. In my lecture, I will highlight novel light-based technologies that enable addressing these questions with unprecedented precision. First of all, we engineered a system to control the transport and positioning of intracellular components with light through the controlled recruitment of specific motor proteins. This allows us to directly explore the intracellular activity of motor proteins and the functional consequences of organelle mislocalization. In addition, I will introduce a new method to super-resolve microtubules and directly assign their polarity. Together, these technologies hold great promises for exploring cellular organization and dynamics in health and disease.
Tuesday 11 October 2016 à 11h30, Salle des Thèses.
Unraveling the role of C-fibers in responding to inflammatory and nutritional challenges
Laurent Gautron (University of Texas Southwestern Medical Center, USA)
Physiological homeostasis is monitored and maintained by a complex system of neurons, including peripheral sensory neurons, which convey information from metabolic tissues to the brain. Of particular importance are Nav1.8-expressing afferents (C-fibers) which serve as a critical link between peripheral nutrient sensing and centrally mediated physiological responses. My laboratory is interested in the physiological requirements for Nav1.8-expressing neurons in regulating metabolic inflammation. Furthermore, we examine how inflammatory insults and high-fat feeding affects the anatomical integrity of Nav1.8-expressing neurons supplying the gastrointestinal tract, with a special emphasis on the role played by bacterial endotoxins and the Toll-like receptor 4. Together, these studies will increase our understanding of the biological control of energy balance, feeding and metabolic inflammation and will provide mechanistic insights to the pathophysiology of obesity-associated neuropathies
Friday 7 October 2016 à 11h30, Salle de conférence.
In vitro evolution of modified DNA enzymes
Marcel Hollenstein, CNRS UMR3523, I. Pasteur, Paris
Friday 7 October 2016 à 11h, Amphi Giroud.
Programming the Cerebral Cortex: from Cortical Development to Cortex in the Dish
Paola Arlotta (Harvard Stem Cell Institute, MA, USA)
The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of several neuron subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the coordinated expression of these unique combinations of genes is not known for any class of cortical neurons. I will discuss recent work on the identification of novel transcriptional dynamics underlying developmental generation of excitatory pyramidal neuron diversity in the cerebral cortex, and highlight some new governing principles that regulate interactions among pyramidal neuron classes, with a particular emphasis on oligodendrocytes and regulation of myelination. Finally, I will discuss new work aimed at modeling development and disease of the human cerebral cortex, in 3D cerebral organoids generated from human pluripotent stem cells
Friday 30 September 2016 à 11h30, Salle de conférence.
Probing Visual Perception Outside of Conscious Awareness
Randolph Blake (Vanderbilt University, TN, USA)
Conscious visual awareness seems to occupy center stage in our perceptual world, guiding our actions and channeling our thoughts. But is that impression a misleading illusion? To rephrase the question in a tractable form, what aspects of visual processing transpire outside of awareness? Psychologists have at their disposal an arsenal of techniques for dissociating optical input and visual awareness, and my talk will touch on the strengths and weaknesses of some of those techniques. But I’ll focus primarily on the beguiling phenomenon called binocular rivalry, wherein perceptual dominance fluctuates between conflicting visual images presented separately to the two eyes. I will highlight some surprising discoveries that have been made using rivalry to dissociate physical stimulation from perceptual awareness, including the impact of affective and semantic content on suppression of a stimulus from awareness. I will close by describing results illuminating possible neural concomitants of fluctuations in visual perception during rivalry and will offer some thoughts on the implications of those results for the larger question of neural correlates of consciousness
Friday 23 September 2016 à 11h30, Salle de conférence.
Synaptic plasticity in GABAergic inhibitory cells of the dentate gyrus
Marlene BARTOS, Institut for Physiology I, in Freiburg (Germany).
Monday 19 September 2016 à 11h, Salle de conférence.
Event-related brain potential (ERP) evidence for Immedicacy, Incrementality, prediction, and the role of context
Marta Kutas (University of California San Diego, CA, USA)
Significant neuro-cognitive work takes place at the language-memory interface that supports word and sentence processing. Both the content and the functional organization of our knowledge influence language comprehension in real time. Each cerebral hemisphere seems to be involved, albeit in different ways. The nature of the functional organization of our knowledge (associative, categorical, events, perceptuo-motor) and their use in predictive and/or integrative language processing have been revealed via investigations employing event-related brain potentials (ERPs). I will review some of our electrophysiological work supporting the idea that language processing is immediate and incremental, context-driven, sometimes predictive, multi-modal, and bi-hemispheric.
Friday 16 September 2016 à 11h30, Salle de conférence.
The inhibitory microcircuit in mouse presubiculum: from interneuron properties to input-output connectivity
Friday 16 September 2016 à 14h, Salle des Thèses.
Differential embedding of hippocampal output neurons during high-frequency oscillations
Prof. Dieter SCHMITZ, from the Charité – Universitätsmedizin in Berlin (Allemagne)
Memory consolidation is dependent on hippocampal activity patterns, so called hippocampal ripples. During these fast oscillations, memory traces are transferred from the hippocampus to the neocortex via the subiculum. We investigated the role of single cells in the subiculum during ripples and found that, dependent on their subtype, they are preferentially activated or inhibited. In addition, these two subtypes, the bursting and regular firing type, are differentially integrated into the local network: inhibitory cells are more densely connected to regular firing cells, and communication between regular and bursting cells is unidirectional. Together with earlier findings on different preferential target regions of these subtypes, we conclude that memory traces are guided to target regions of the activated cell type.
Thursday 15 September 2016 à 17h15, Salle de conférence.
Genetic architecture of autism: from gene discovery to functional dissection of rare mutations
Catalina Betancur, Institut de Biologie Paris-Seine, Université Pierre et Marie Curie
The genetic architecture of autism spectrum disorder (ASD) is highly heterogeneous and involves hundreds of loci, each contributing to a very small fraction of cases. To date, a genetic etiology is identified in ~20% of the patients, including chromosomal rearrangements, copy number variants (CNV) and sequence variants. All these abnormalities are rare, and often occur de novo. Despite this heterogeneity, many genes converge in functional pathways, providing therapeutic targets. In particular, a large number of genes implicated in ASD are involved in synaptic function. Many of the genetic variants identified in ASD confer risk for a broad range of neurodevelopmental and neuropsychiatric disorders, including intellectual disability and epilepsy. In my talk, I will discuss what we have learned about the causes of autism and the questions that remain unanswered.
Tuesday 13 September 2016 à 11h, Salle de conférence.
Seeing and controlling information flow through GTPase networks
Klaus Hahn (University of North Carolina, NC, USA)
Signaling proteins can produce essentially opposite cell behaviors depending on subtle differences in activation kinetics or transient localizations. To understand signaling controlled by spatio-temporal dynamics we have devised approaches to visualize and manipulate signaling networks in living cells and animals, including what we believe are broadly applicable methods to control proteins with light. The role of Rho family GTPase circuits in regulating motility is being probed using engineered allosteric switches to photoinhibit or photoactivate guanine exchange factors, kinases, and GTPases. Success with three different protein families leaves us optimistic that there is a simple way to identify and control allosteric networks with light or small molecules. LOVTRAP, a method for light-controlled sequestration and release of proteins, will also be described. LOVTRAP has been applied to modulate and dissect oscillating cellular circuits
Friday 9 September 2016 à 11h30, Salle de conférence.
Lewis base catalysis of asymmetric acylation, sulfonylation and phosphorylation processes
Pr. Alan C Spivey (Imperial College, London)
Monday 11 July 2016 à 11h, Salle de conférence.
Valorisation de la Recherche Publique
Lydie Viatte, Chef de projet en Santé, SATT IdF Innov
Thursday 7 July 2016 à 11h, Salle de conférence.
Deciphering autophagy regulation in cancer; novel mechanisms and opportunities for therapeutic exploitation
James Murray, Trinity College Dublin, the University of Dublin, Ireland
Autophagy underpins cellular homeostasis. As a cell survival pathway, autophagy removes damaged cellular components, preventing the buildup of nonfunctional organelles, proteins and toxic small molecules. In disease, autophagy is frequently dysregulated, especially in diseases associated with ageing. Our laboratory is engaged in basic research of the mechanisms of autophagy control, in normal and diseased cells. In particular, one area we are investigating how the signalling proteins that control cell growth also regulate autophagy in the context of cancer. Research from our laboratory has identified new mechanisms of autophagy regulation that are relevant to disease, which we hope to translate towards new targeted therapeutics for the treatment of cancer
Thursday 30 June 2016 à 11h, Salle des Thèses.
Changement climatique et santé
Denis BARD (Président de la SFSE, Professeur à l’Ecole des Hautes Etudes en Santé Publique)
la Société française Santé et Environnement organise une conférence-débat grand public qui permettra de : – sensibiliser le public à l’impact (à plus ou moins long terme) du changement climatique sur la santé des populations, – s’informer sur les dernières connaissances sur ce sujet, – débattre avec des spécialistes du domaine et échanger sur les moyens d’agir individuellement et collectivement (penser global, agir local !). Conférence animée par Denis BARD (Président de la SFSE, Professeur à l’Ecole des Hautes Etudes en Santé Publique) Inscription sur le site : http://sfse.org/article/conference-grand-public-2016
Wednesday 29 June 2016 à 17h, Amphi Weiss.
Dynamics of SNARE-mediated single fusion pores in a biochemically defined system
Erdem Karatekin, Yale University, New Haven, CT, USA
Monday 27 June 2016 à 11h, Salle de conférence.
From Vision to Decision and Navigation in Mouse Cortex
Matteo Carandini (University College London, UK)
As signals progress along the early visual system, they undergo a remarkable transformation. Before reaching the primary visual cortex (V1) responses are still highly repeatable, and they can be predicted by simple model of image processing. In V1, instead, responses become hugely affected by activity that originates within the brain, which varies from trial to trial, and is closely related to behavior. For instance, a major factor that controls responses of neurons in the mouse visual cortex is locomotion. In mouse V1, locomotion changes the nature of spatial integration, reducing the strength of lateral interactions. Moreover, locomotion interacts with vision to affect responses during navigation, perhaps to help the animal estimate is own movement. In the parietal visual areas that follow V1, the visual signals are transformed to encode variables relevant to navigation. We study this transformation by training mice to make visual decisions while they navigate in a virtual reality environment. Preliminary results indicate that these neurons code for combinations of the animal’s heading and position in the room. The activity of neurons in parietal cortex of the mouse thus reflects the interactions of vision, decision, and navigation.
Friday 24 June 2016 à 11h30, Salle de conférence.
Cortical GABAergic neurons and their connections
Yoshiyuki KUBOTA, from the National Institute for Physiological Sciences, Division of Cerebral Circuitry, in Okazaki.
Friday 24 June 2016 à 10h30, Salle H335.
Fetal stress and epigenetic regulations in the normal and diseased developing brain
Valérie Mezger (University Paris Diderot, France)
We aim to understand the links between environmental stress and brain development and integrity. There is an almost complete black box between the observation that fetal stress is a factor of predisposition to brain disabilities and the resulting emergence of associated cognitive and affective disorders. In particular, the molecular mechanisms underlying the short- and long-term effects of fetal stress in the etiology of these disabilities are largely unknown. We address this question by studying Heat Shock Factors that represent a unique entry point into a link between stress, epigenetics, and brain development/integrity. Importantly, we demonstrated that HSF2 is involved in brain cortical development. Using fetal alcohol exposure (FAE) as a paradigm of prenatal stress in mouse models, we investigate whether HSFs could contribute to the deposition of short- and long-term epigenetic marks. 1) We showed that HSF2 is an essential mediator of neuronal migration defects characteristic of Fetal Alcohol Syndrome, in response to FAE in the developing brain. 2) We unravelled a dynamic interplay between HSF2 and HATs, quickly followed by interactions between HSF2 and HDAC1/2 during stress. 3) We unravelled a crosstalk between HSFs and the expression of epigenetic actors whose expression can be disturbed by stress in an HSF-dependent manner. We are currently investigating how the HSF-dependent deposition of epigenetic marks upon fetal stress, via the formation of these complexes or disturbances in DNA methylation, is susceptible to lead to long-term disturbances of HSF2 target genes that are involved not only in neuronal migration, but also in brain abilities via the control of neurite growth and neuronal plasticity.
Friday 17 June 2016 à 11h30, Salle de conférence.
Development and use of chemical tools to modulate gene expression in cancer cells
Paola Arimondo (ETaC, Toulouse)
Thursday 16 June 2016 à 14h30, Salle de conférence.
Rôle de SUMO (Small Ubiquitin-like Modifier protein) dans la réponse à l’interféron et la défense antivirale
Ghizlane MAARIFI, UMR-1124, Université Paris Descartes
Wednesday 15 June 2016 à 14h, Salle de conférence.
Active vision: The inseparable link between perception and action
Michele Rucci (Boston University, MA, USA)
Our eyes are never at rest. Rapid gaze shifts (saccades) occur 2-3 times per second, and we are normally not aware that eye movements continually occur even during the inter-saccadic periods of « fixation », the very periods in which visual information is acquired and processed. In this talk, I will argue that the incessant motion of the eye is a critical information processing stage: a computational element of an active sensorimotor strategy by which the visual system processes spatial information in the temporal domain. I will review recent experimental and theoretical findings to address three main questions: (1) How is spatial information encoded in the modulations of luminance resulting from eye movements? (2) How is this information extracted and interpreted? (3) Can this stage of processing be tuned to the task via motor control? The proposal that the visual system actively represents space through time replaces the traditional notion of the early visual system as a passive encoding stage that optimizes overall information transmission with that of an active, tunable system for feature extraction, whose function can be fully understood only in conjunction with eye movements. It implies that motor behavior is in part responsible for fundamental properties of spatial vision that are, at present, solely attributed to neural mechanisms
Friday 10 June 2016 à 11h30, Salle de conférence.
Transcription factors, mitosis and epigenetics in pluripotent cells
Pablo Navarro Gil, Institut Pasteur, Paris
How pluripotent cells such as mouse ES cells maintain their biological identity over virtually infinite cell divisions remains unclear, in particular because classical epigenetic regulators have been shown to be dispensable in terms of ES cell self-renewal. I will describe how we think ES cells reproduce efficiently their gene expression program after each cell division
Thursday 9 June 2016 à 11h, Salle de conférence.
ANNULE Preferential vulnerability of the striatum in Huntington’s disease: past and new hypotheses
Emmanuel BROUILLET, UMR 9199 CEA-CNRS-PARIS-SUD UNIVERSITY
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation of the huntingtin gene. The main hallmark of HD is the early loss of medium-sized spiny neurons (MSNs) from the striatum. The mechanisms underlying the preferential damage to the striatum are unknown. We will briefly review the main hypothetical mechanisms that could explain striatal degeneration in HD and will focus on novel findings recently obtained in the lab. We identified about 120 genes preferentially expressed in the striatum from a transcriptome SAGE analysis of different brain regions. A number of these striatal genes displays significantly lower than normal levels of expression in the brains of HD patients or in mouse models of HD. However, their functions are frequently unknown, and their potential roles in the vulnerability of the striatum in HD remain a matter of speculation. Our lab recently focused on a particularly interesting candidate called DCLK3, the third member of the Doublecortin-like kinase (DCLK) family. Our recent work based on different approaches (genetic mouse models of HD, human cell models, viral vectors-mediated gene transfer, DCLK3 mutants) indicates that the loss of DCLK3 could play a key role in HD pathogenesis and provide key insight into the potential functions of this newly identified kinase in neurons.
Tuesday 7 June 2016 à 11h, Amphi Lavoisier A.
Cellules souches neuronale et mésoblastiques: microARN et voies de signalisation impliqués dans le contrôle des fonctions cellulaires
Anne Baudry, Université Paris Descartes – Inserm UMR-S 1124
Tuesday 7 June 2016 à 14h, Salle de conférence.
Specific synaptic processing in cerebellar modules
Philippe Isope (Institute of Neurosciences, Strasbourg, France)
Neuronal networks are often organized in local circuits or modules that serve different functions in specific brain regions. A given cortical area is composed of many functional modules that allow a parallel processing of incoming information. One major challenge is to unravel the operational modes of these modules. The cerebellum plays a major role in the control and learning of skilled movements. To understand the integrative role of the cerebellum in the motor circuit its input/output transformation needs to be elucidated. Although the cellular organization of the cerebellar cortex looks homogeneous across lobules and folia, anatomical and molecular data have shown that the cerebellum is also organized in modules. Functional studies have demonstrated that task-related modules can be identified and selectively modified. However rules governing how incoming information is channeled through cerebellar modules and how the specific processing of one given input is carried out by the microcircuits are still poorly understood. Furthermore, the functional synaptic connectivity within and across individual modules has not yet been characterized. I will present our recent findings that can shed light on the modular organization of synaptic integration properties in the cerebellar cortex
Friday 3 June 2016 à 11h30, Salle de conférence.
Autophagy in CNS synapses
David Sulzer (Columbia University, NY, USA)
“Autophagy” is used to mean the degradation by a cell of its own components within lysosomes. Not long ago, this process was widely accepted to be absent from neurons, but recently the regulation of neuronal autophagy has been implicated in an enormous range of normal and disease mechanisms. We have identified autophagic regulation of presynaptic and postsynaptic function, including the ability to degrade synaptic vesicles and thereby regulate neurotransmitter release. The normal net pruning of cortical synapses over development is apparently due in part to neuronal autophagic pathways, and disturbances in this process may provide for convergent pathways that underlie central aspects of autism and forms of epilepsy
Friday 27 May 2016 à 11h30, Salle de conférence.
TRPC3-dependent synaptic transmission in central mammalian neurons
Arthur Konnerth (Institute of Neuroscience, Munich, Germany)
The metabotropic glutamate receptor type 1 (mGluR1) is highly expressed in Purkinje cells (PCs) of the mammalian cerebellum. At parallel fiber-PC synapses, activation of mGluR1 evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from endoplasmic reticulum (ER) Ca2+ stores (Takechi et al., Nature, 1998) and a slow excitatory postsynaptic potential (sEPSP) (Batchelor and Garthwaite, Neuropharmacology, 1993). A few years ago, in collaboration with Lutz Birnbaumer, we demonstrated that the sEPSP is mediated by the transient receptor potential (TRPC) channel subunit TRPC3 (Hartmann et al., Neuron 2008). However, the link of mGluR1 to its downstream effectors remained unknown. We recently tested the possible involvement of the stromal interaction molecule 1 (STIM1), known to interact in non-excitable cells with TRPC channels. Using quantitative single cell RT-PCR and immunostaining, we determined that STIM1 is ten times more abundant than its homolog STIM2 in PCs. We then demonstrated in a newly generated knockout (STIM1pko) mouse line that the PC-specific deletion of Stim1 caused impairments in cerebellar motor behavior. On the cellular level, we found that in STIM1pko mice, ER Ca2+ stores are largely depleted. Surprisingly, also mGluR1-dependent TRPC3-mediated currents were largely suppressed (Hartmann et al., Neuron, 2014). Together, these results demonstrate that in mammals STIM1 is a key regulator of neuronal Ca2+ signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination.
Friday 20 May 2016 à 11h30, Salle de conférence.
The in vivo imaging platform: Relevance for R&D in biotech and big Pharma
Philippe Clément-Lacroix, Directeur de Pharmacologie in vivo chez Galapagos
The pharmaceutical industry is facing tremendous pressure, as a result of public perception, regulatory hurdles, and the intricacies of research and development (R&D). The latter two are significant in that they affect the number of drugs that may be registered by regulatory authorities, the time to discover and develop drugs, and the cost of drug development. Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities could be crucial to observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging modalities that are non-invasive and in vivo have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Optical imaging is fast and easy to perform, and is relatively inexpensive compared to many of the other imaging modalities. Furthermore, it is extremely sensitive, being able to detect molecular events. For all these reasons which contribute to accelerate, to consolidate the data and minimize the cost and the animal using, In vivo imaging are now clearly integrated in the pharmaceutical industry.
Friday 20 May 2016 à 13h30, Salle de conférence.
CLC Cl- channels and transporters from molecular biophysics to human genetic disease
Michael PUSCH, Biophysics Institute, National Research Council, Genoa, Italy
Cl- ions are physiologically relevant in most organisms, and, consequently, a multitude of different Cl- transporting membrane proteins has evolved. In mammals, 9 CLC genes code for the plasma-membrane localized Cl- channels (CLC-1, CLC-2, CLC-Ka and CLC-Kb) and Cl-/H+ antiporters (CLC-3 to -7) localized in the membrane of intracellular endosomes/lysosomes. Several CLC genes (or their respective beta subunits) are involved in human genetic diseases. The presentation will focus on two different CLC channels. CLC-K channels are basolaterally expressed in the kidney and in the inner ear, where they are involved in Cl- reabsorption and in endolymph production, respectively. CLC-K channels are unique among all CLC proteins in that their activity is dependent on the extracellular Ca2+ concentration. We identified a Ca2+ binding site that is formed by acidic residues at the intersubunit interface of the dimeric channel. Ca2+ regulation might be physiologically relevant as the thick ascending loop is involved in Ca2+ reabsorption. The CLC-2 channel is rather ubiquitously expressed in epithelial and non-epithelial cells. Recently, we discovered that, in glia, CLC-2 associates with the glia specific cell adhesion molecule GlialCAM. GlialCAM also associates with the membrane protein MLC1, and mutations in GlialCAM and in MLC1 cause a rare form of leukodystrophy. GlialCAM induces clustering of CLC-2 at cell-cell contacts and reduces its inward rectification. We investigated the biochemical and functional interaction between GlialCAM and CLC-2 and identified the relevant regions of GlialCAM involved in clustering and functional activation
Tuesday 17 May 2016 à 11h, Salle des Thèses.
Mouse models of Charcot-Marie-Tooth peripheral Neuropathy: towards disease mechanisms and therapeutic strategies
Robert Burgess (Jackson Laboratory, ME, USA)
In 2006, the Burgess lab discovered mice with an autosomal dominant mutation in /Gars/ (glycyl tRNA synthetase), resulting in peripheral axon degeneration. These mice create a model of the human disease Charcot-Marie-Tooth type 2D, and we have used a combination of genetic and biochemical approaches to understand the underlying disease mechanism and to pilot therapeutic approaches. These studies will have implications for other forms of Charcot-Marie-Tooth disease, and possibly other heritable neuromuscular disorders and motor neuron diseases.
Friday 13 May 2016 à 11h30, Salle de conférence.
Neuronal circuits for dynamic auditory processing and learning
Maria Geffen, University of Pennsylvania
Monday 9 May 2016 à 11h30, Salle de conférence.
New technologies available on the Cell Imaging Core Facility of Necker Institute
Meriem Garfa-Traore (Head of the Cell Imaging Core Facility of Necker Institute)
The Cell Imaging Core Facility of the “Structure Fédérative de Recherche Necker Enfants Malades” is specialized in the visualization and analysis of the structure and dynamic processes at the cellular and tissue level until the organism level. In recent years, optical microscopy has evolved considerably with the emergence of super-resolution microscopy and light sheet microscopy. Thanks to funding from the Imagine Institute, the platform could be equipped with these new technologies that I will briefly present, illustrated by research applications
Friday 22 April 2016 à 13h30, Salle de conférence.
creation of the placenta and fetal clinical imaging research platform (the LUMIERE projet)
Pr Laurent Salomon (Service de Radiologie Hôpital Européen Georges Pompidou)
Friday 22 April 2016 à 13h30, Salle de conférence.
Collective patterns resulting from social behavior
Jean-Louis Deneubourg (Université libre de Bruxelles, Belgium)
Information processing in decentralized systems is a core concept in biology and, in particular, in social and gregarious arthropods. A key question is how a collective decision emerges and how its resulting spatial pattern contributes to the information storage and processing by the group members. An essential feature of such systems is the existence of a diversity of spatial patterns and collective responses depending on a subtle interplay between individual interactions and environmental constraints. We will explore different situations where the environmental characteristics shape the decisions at the collective level. Experimental and theoretical approaches demonstrate that (1) collective choices can emerge through interactions between identical individuals without a perfect knowledge of the entire environment or in absence of leadership; and (2) individuals within a group dramatically outperform the problem solving ability of one single individual. We will also discuss how the complexity at the individual level and the subsequent functionality increase the efficiency of the collective response. Our research points towards a generic self-organized collective decision-making process shared by many group-living organisms
Friday 15 April 2016 à 11h30, Salle de conférence.
L’interféron béta dans la réponse antivirale innée et la maladie d’Alzheimer
Eliette Bonnefoy (UMRS Inserm 1007, CICB-Paris, Université Paris Descartes)
Thursday 14 April 2016 à 11h, Salle de conférence.
A basal ganglia output for evaluation of action outcomes
Bo Li, Cold Spring Harbor Laboratory, New York, USA
The habenula-projecting globus pallidus (GPh), a phylogenetically conserved non-motor output of the basal ganglia, has recently emerged as a key controller of the brain’s reward system. It excites the lateral habenula (LHb) that, in turn, drives inhibition onto dopamine neurons when an outcome is worse than expected, and is thus thought to provide the “prediction error” signal essential for learning to avoid unrewarding actions. However, whether the GPh contributes to such a learning process has never been examined, and consequently how it influences behaviour remains unclear. Here we show that the GPh plays a more fundamental behavioural role than currently believed, as it is critical for reinforcing behaviours that lead to reward as well as discouraging those that do not. We found in a classical conditioning task that individual mouse GPh neurons were inhibited or excited, respectively, when an outcome was better or worse than expected. Mimicking these prediction error signals with optogenetic inhibition or excitation was sufficient to drive positive reinforcement or punishment in a probabilistic switching task. Moreover, cell-type-specific synaptic manipulations revealed that the inhibitory and excitatory inputs to the GPh are necessary for mice to appropriately respond to positive and negative feedback, respectively. Our results provide the first direct evidence that the GPh conveys both positive and negative evaluation signals to update the expected value of actions during reinforcement learning
Monday 4 April 2016 à 11h, Salle de conférence.
Two forms of plasticity triggered by enzymatic removal of extracellular matrix in the hippocampus
Inseon Song, German Center for Neurodegenerative Diseases, Magdeburg, Germany
The neural extracellular matrix (ECM) bi-directionally regulates synaptic plasticity but the mechanisms supporting tenacity versus plasticity remain elusive. We previously showed that acute enzymatic removal of ECM by chondroitinase ABC (ChABC) impaired long-term potentiation (LTP) in CA3-CA1 synapses by decreasing excitability of CA1 pyramidal neurons (Dembitskaya et al.,2014 FENS). In continuation of this finding, here we showed this effect was mediated by a loss of ECM molecule brevican, which triggered upregulation in cell surface expression of the small-conductance (SK) family of Ca2+ activated K+ channels. Pharmacological blockade of SK channels in ChABC-treated or brevican knockout slices normalized neuronal excitability and promoted LTP and object recognition. Surprisingly, LTP recorded after enzymatic ECM removal in the presence of SK-channel blocker was enhanced relatively to control. This enhancement was abrogated by function-blocking b1 integrin antibodies and inhibition of Rho-associated protein kinase (ROCK). Our findings demonstrate that the brevican-SK pathway dominates over the b1 integrin-ROCK pathway in control of tenacity/plasticity in the hippocampus, and open new combinatorial options to boost plasticity by targeting ECM and SK channels
Thursday 31 March 2016 à 10h, Salle de conférence.
Focusing light into biological tissues with wavefront shaping
Changhuei Yang (Caltech, CA, USA)
I will discuss two lines of wavefront engineering work going on in my group. Time-Reversal Optical Focusing – We appear opaque because our tissues scatter light very strongly. Traditionally, focusing of light in biological tissues is confounded by the extreme scattering nature of tissues. Interestingly, optical scattering is time-symmetric and we can exploit optical phase conjugation methods to null out scattering effects. I will discuss our recent results in using different types of guidestar methods in combination with digital optical phase conjugation to tightly focus light deep within biological tissues. These technologies can potentially enable incisionless laser surgery, targeted optogenetic activation, high-resolution biochemical tissue imaging and more. Fourier Ptychography – Microscopes are complex and fussy creatures that are capable of delivering limited image information. This is because physical optical lenses are intrinsically imperfect. The perfect lenses we draw in high school ray diagrams simply do not exist. I will discuss our recent work on Fourier Ptychographic Microscopy – a computational microscopy method that enables a standard microscope to push past its physical optical limitations to provide gigapixel imaging ability
Friday 25 March 2016 à 11h30, Salle de conférence.
The scientific basis of new clinical tests of peripheral vestibular function
Ian S. Curthoys, University of Sydney, Australia
I plan to talk about new developments in clinical testing of semicircular canal and otolith function – showing how basic science from animal research, anatomy, physiology and control patients – underpins clinical testing. The video head impulse test (vHIT), now allows the testing of the function of all semicircular canals. Vertical canal function testing has now revealed that some patients have bilateral vestibular loss, a result previously impossible to detect with caloric testing. We have developed a new version of vHIT where a simple change in the instructions makes the test easier for the patient and the clinician. This new protocol (we call SHIMPs for suppression head impulses) is the perfect complement to the standard protocol (we now call HIMPs) and the protocol and its explanation will be presented. The new tests of otolithic function – measuring vestibular evoked myogenic potentials (VEMPs) to air conducted sound (ACS) and bone conducted vibration (BCV) – are built on evidence from physiology as to what otolithic receptors are activated by these stimuli. Why is sound an otolithic stimulus at all? Neural recordings show the answer: ACS and BCV activate irregular otolithic afferents up to high frequencies (>1000Hz), probably by causing fluid displacement which deflects the short stiff cilia of the striolar type I receptors. The very fast dynamics of these unique receptors and afferents allow them to respond and phase lock to the stimulus waveform up to very high frequencies with very short latency and very fast recovery. After a semicircular canal dehiscence (SCD) previously unresponsive canal neurons are phase locked to high frequencies and also show responses to high frequency ACS indicating sustained cupula deflection. This physiological evidence explains the enhanced VEMP responses to ACS and BCV, the Tullio phenomenon and provides the scientific basis for the clinical test – vibration induced nystagmus
Monday 21 March 2016 à 11h30, Salle de conférence.
FULL FIELD OPTICAL COHERENCE TOMOGRAPHY AS A DIAGNOSIS TOOL
Pr. Claude Boccara (Institut Langevin ESPCI-ParisTech)
In this seminar we will discuss the principle and a few application of full field OCT (FFOCT) in cancer diagnosis. We will compare the images of “virtual” optical slices obtained through biological tissue with histology and discuss some other contrast mechanisms able to provide valuable complementary information to FFOCT. Finally we will discuss a new approach based on the cell metabolism that exhibits a new kind of contrast to our tomographic images
Friday 18 March 2016 à 13h30, Salle de conférence.
Functions of Scaffold Protein Rapsyn in Clustering nAChRs and Positioning Lysosomes
Professor Mohammed Akaaboune, University of Michigan
Monday 14 March 2016 à 10h30, Salle de conférence.
Writing and consolidating memories
Pico Caroni (FMI, Basel, Switzerland)
I will discuss recent, mostly unpublished work from our lab that provides evidence for the existence of two temporally defined time windows to regulate memories after learning. During the first time window new information can be added to memories, whereas during the second time window memories are long-term consolidated. I will discuss circuit, cellular and molecular mechanisms that control these critical processes in learning and memory
Friday 11 March 2016 à 11h30, Salle de conférence.
MicroARNs et maladie d’Alzheimer: mécanismes moléculaires, facteurs de risque, diagnostic et traitement
Sébastien Hebert (Université Laval, Québec)
Friday 11 March 2016 à 14h, Salle des Thèses.
Healthy aging by muscle mitochondrial stress adaptation?
Susanne Klaus (German Institute of Human Nutrition, Potsdam, Allemagne)
Thursday 10 March 2016 à 11h, Salle de conférence.
The Biology of axonal and synaptic Power Supplies
Timothy RYAN (Cornell University, New York)
Thursday 10 March 2016 à 11h30, Salle des Thèses.
Evidence for dual cortical processes in vestibular integration
Jocelyne Ventre-Dominey (Stem-cell and Brain Research Institute, Lyon, F)
A number of behavioural and neuroimaging studies have reported converging data in favour of a cortical network for vestibular function, distributed between the temporo-parietal cortex and the prefrontal cortex in the primate. In this talk we will review the role of the cerebral cortex in visuo- vestibular integration with particular interest on the temporo-occipital and parietal regions. I will present results supporting the idea of two separate cortical vestibular sub-systems involved in distinct aspects of vestibular functions
Friday 19 February 2016 à 11h30, Salle de conférence.
Synapse Identity in cerebellar Purkinje cells: Role of the C1QL1/BAI3 complex
Séverine Sigoillot, Center for Interdisciplinary Research in Biology (CIRB) – Collège de France; CNRS UMR7241; INSERM U1050, Paris, France.
Proper innervation by specific afferents on a given neuron is required to obtain a functional neuronal network. During development, synaptogenesis shows an exquisite specificity in terms of partner selection and choice of innervating territory. My recent results show that the specific expression of the complement-related protein C1QL1 by one of the two excitatory afferents of Purkinje cells underlies its proper connectivity. This specification of the afferent territory requires the interaction of C1QL1 with the postsynaptic receptor BAI3. The connectivity by the second excitatory afferent of Purkinje cell involves another complement/receptor complex: CBLN1/GluRdelta2. These results strengthen the idea that each type of connection possesses a specific synaptic identity, a concept that, albeit proposed by Sperry in 1963, has never been formally proven until now.
Friday 5 February 2016 à 11h30, Salle de conférence.
Conception de ligands d’ARN : pourquoi, comment ?
Laurent Micouin, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (UMR 8601), CICB-Paris (FR3567)
Thursday 4 February 2016 à 11h, Salle de conférence.
Journée interdisciplinaire UFRs Math-info et Biomédicale
Christine Graffigne et Charbel Massaad
Friday 22 January 2016 à 9h, Salle de conférence.
Instabilité posturale chez les seniors : dysfonction vestibulaire périphérique ou centrale ?
Elodie CHIAROVANO, UMR8257 COGNAC G
Friday 22 January 2016 à 14h30, Salle des Thèses.
Advanced optical methods for fast and three-dimensional control of neural activity
Friday 22 January 2016 à 14h, Salle de conférence.
Blunting the Spinal Muscular Atrophy Disease phenotype in a C. elegans model system
Thursday 21 January 2016 à 11h, Salle des Thèses.
Nouvelle approche neuroprotectrice et remyélinisante par l’étazolate dans le système nerveux central : Implication des α-sécrétases (ADAM10)
Wednesday 20 January 2016 à 14h, Salle de conférence.
COnical Diffraction Microscopy
L.Philippe BRAITBART, Ph.D., (Président/CEO and co-founder BIOAXIAL)
BioAxial develops, manufactures and markets a super-resolution instrument for the life sciences and medical research communities. After several years of research and development, BioAxial launched a breakthrough solution based on COnical DIffraction Microscopy (CODIM) which boosts the resolution of confocal microscopes. Thanks to a unique combination of fluorescence microscopy, crystal optics and algorithms, the BioAxial’s instrument can image fixed and live samples labeled with a broad variety of fluorophores commonly used in confocal microscopy. In addition, research scientists can run time-lapse experiments over extended periods of time without fearing sample damage thanks to the low light energy level necessary to image the samples and therefore the negligible phototoxicity of the technique. Founded in 2010, BioAxial’s offices and labs are located in Paris, France.
Friday 18 December 2015 à 13h30, Salle de conférence.
In Vivo High-Resolution Micro-ultrasound and Photoacoustic Imaging for preclinical Research
Philippe Trochet (FUJIFILM VisualSonics, The Netherlands)
VisualSonics is a manufacturer of real-time, in vivo, high-resolution micro-imaging systems designed specifically for preclinical research and is a wholly owned subsidiary of SonoSite, Inc. VisualSonics’ imaging technologies allow researchers at pharmaceutical and biotechnology companies, hospitals and universities to conduct research in cardiovascular, cancer, neurobiology and developmental biology areas. The micro-imaging technologies support research applications that include genetic research, phenotypic studies and drug development. VisualSonics high-frequency micro-imaging platforms combine high-resolution, real-time in vivo imaging with quantifiable data that have been published in over 850 scientific publications globally. VisualSonics is based out of Toronto, Ontario, Canada with operations in more than 30 countries. European operations are conducted out of Science Park, Amsterdam, Netherlands and Asia Pacific operations out of Singapore.
Friday 18 December 2015 à 13h30, Salle de conférence.
Learning and memory in amygdala circuits
Andreas Lüthi, Friedrich Miescher Institute for Biomedical Research, Basel
Friday 18 December 2015 à 11h30, Salle de conférence.
Environmentally Induced Epigenetic Transgenerational Inheritance of Disease : Ancestral Ghosts in Your Genome
Prof. Michael K. Skinner, Center for Reproductive Biology, School of Biological Sciences, Washington State University
Transgenerational effects of environmental toxicants significantly amplify the impact and health hazards of these compounds. One of the most sensitive periods to exposure is during embryonic gonadal sex determination when the germ line is undergoing epigenetic programming and DNA re-methylation. Previous studies have shown that endocrine disruptors can cause an increase in adult onset disease such as infertility, prostate, ovary and kidney disease, cancers and obesity. Interestingly, this effect is transgenerational (F1, F2, F3 and F4 generations) and hypothesized to be due to a permanent (imprinted) altered DNA methylation of the germ-line. The transgenerational epigenetic mechanism appears to involve the actions of an environmental compound at the time of sex determination to permanently alter the epigenetic (i.e. DNA methylation) programming of the germ line that then alters the transcriptomes of developing organs to induce disease susceptibility and development transgenerationally. A variety of different environmental compounds have been shown to induce this epigenetic transgenerational inheritance of disease including : fungicide vinclozolin, plastics BPA and phthalates, pesticides, DDT, dioxin and hydrocarbons. The suggestion that environmental factors can reprogram the germ line to induce epigenetic transgenerational inheritance of disease and phenotypic variation is a new paradigm in disease etiology that is also relevant to other areas of biology such as evolution.
Thursday 17 December 2015 à 14h, Salle de conférence.
Critical Periods in Speech Perception and Development
Janet Werker, Department of Psychology, The University of British Columbia
The process of language acquisition begins in perceptual development long before infants produce or even understand, their first words. In this talk, I will review the rapid changes in auditory, visual, and multimodal speech perception that occur in the first months of life as infants establish a foundation for language acquisition. I will then present evidence that, while under typical circumstances the timing of perceptual attunement seems to be constrained by maturation, there are identifiable variations in experiences that can accelerate, slow down, or modify this developmental trajectory. Finally, I will introduce new questions about whether or studies to date on the timing of plasticity have considered all the relevant input systems.
Friday 11 December 2015 à 11h30, Salle de conférence.
BRAIN IMMUNE CELLS AND INFLAMMATION IN NEURODEVELOPMENT: from physiology to pathology
Please note that the seminar will include 3 talks : 2 talks delivered by 2 esteemed principal investigators (Dr. Sonia Garel and Dr. Pierre Gressens), and 1 talk delivered by a talented Ph.D. student (Charles Sanson).
Thursday 10 December 2015 à 18h, Salle de conférence.
Neuro-inspired photonics for computing and information processing
Sylvain Barbay, Laboratory for Photonics and Nanostructures – CNRS – UPR20
The amount of data and information stored or exchanged in modern societies is increasing at a very fast rate and one needs efficient technologies to process this information both in terms of speed and energy consumption. Among the possible alternatives, neuro-inspired computing has emerged in the past years as a promising avenue. Neuromorphic (or neuromimetic) systems are computing and processing systems inspired by the architecture and functionalities of the brain and its constituents, the neurons. Brain-inspired computing may be very efficient with respect to traditional approaches for specific tasks such as pattern recognition (image, face, voice…), classification or decision making, and the use of photonic systems may represent a high-speed and low consumption avenue. We will review important results obtained in the past few years in the field of photonic neuromorphic computing and present the latest results obtained at the LPN. We have recently demonstrated that a micropillar laser with intracavity saturable absorber behaves analogously to a biological neuron, but with timescales at least six orders of magnitude faster: it responds in an all-or-none fashion to input stimuli emitting short optical pulses (spikes) . These spikes are analogous to the action potential that can be triggered in biological neurons. This system also displays an absolute and a relative refractory period as well as the property of temporal summation . It behaves thus as an integrate-and-fire neuron, a model of neuron widely used in computational neuroscience. I will give perspectives to this work in the framework of photonic spike processing, artificial optical neural networks and neuromimetic processing.
Friday 4 December 2015 à 14h15, Salle des Thèses.
Dendritic and myeloid cell activation during HIV infection
Anne Hosmalin, Institut Cochin
The laboratory investigates the effects of HIV infection on dendritic cells and on pro-inflammatory monocytes in different cohorts of patients, trying to unravel protective from deleterious functions.
Wednesday 2 December 2015 à 14h, Salle de conférence.
Thèse : les modulations du métabolisme et de l’autophagie induite par un exercice physique dans un modèle murin de sclérose latérale amyotrophique (SLA)
Friday 27 November 2015 à 10h, Salle des Thèses.
Understanding HIV transcription : Implications for HIV Cure
Monsef Benkirane, Institut de Génétique Humaine (IGH) de Montpellier
Thursday 26 November 2015 à 11h, Salle de conférence.
mTOR inhibitor-based pharmacotherapies for aging-related and neuropsychiatric disorders
Dan Ehninger, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Wednesday 25 November 2015 à 11h, Salle de conférence.
In vivo imaging of axon dismantling and its subcellular correlates
Thomas Misgeld, Professor, Institute of Neuronal Cell Biology, Technical University of Munich
In my talk I will discuss how structural and functional *in vivo* imaging in transgenic mice can be used to analyze the cell biological mechanisms underlying axon dismantling. Specifically I will present data on how assays of organelle dynamics and function can be applied to settings of axon dismantling in development and disease.
Friday 20 November 2015 à 11h30, Salle de conférence.
Synaptic plasticity at a hippocampal associative neural circuit
Pablo E. Castillo, MD/PhD, Albert Einstein College of Medicine, New York (USA)
Friday 20 November 2015 à 16h, Salle de conférence.
Design of Photochemical Tools: Applications from Material Sciences to Neurosciences
Alexandre SPECHT, Laboratoire de Conception et Application de Molécules Bioactives, Univ Strasbourg
Thursday 19 November 2015 à 11h, Salle de réunion UMR8601.
Thèse : Etude moléculaire du TNF-Related Apoptosis Induced Ligand (TRAIL) et de l’activation du Toll-Like Receptor 7 (TLR7) dans les cellules dendritiques plasmacytoïdes (pDC) lors de la réponse antivirale
Monday 9 November 2015 à 15h, Salle de conférence.
COMPUTATIONAL AND THEORITICAL NEUROSCIENCE TO STUDY INFORMATION PROCESSING
The ENP seminar series are intended (i) to provide the masters and graduate ENP students, but also students of other programs, with a progress on exciting areas of contemporary neurosciences, the latest trends and cutting-edge findings, and (ii) to provide students with an opportunity to learn and discuss with the speakers and potentially identify better what subfield of neuroscience they want to study during they Ph.D. Postdoctoral researchers as well as senior investigators are also warmly welcomed to attend the ENP seminar series! Please note that the seminar will include 3 talks : 2 talks delivered by 2 esteemed principal investigators (Dr. Valerie Ego-Stengel and Dr. David Hansel), and 1 talk delivered by a talented Ph.D. student (Flora Bouchacourt).
Thursday 5 November 2015 à 18h, Salle de conférence.
Plate-Forme Cochin Imagerie, de la molécule à l’organe
Pierre Bourdonne, Plate-Forme Cochin Imagerie
Friday 16 October 2015 à 13h30, Salle de conférence.
La plateforme d’Imageries du Vivant de Paris Descartes, PIV, multisite et multimodale
Bich-Thuy Doan, UTCBS – Chimie ParisTech et Université Paris Descartes
Friday 16 October 2015 à 13h30, Salle de conférence.
Autophagy and plasma membrane domains
Patrice Codogno, Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253
Wednesday 14 October 2015 à 10h30, Salle de conférence.
Recent progress toward high-performance neural prosthetics
Andrew Schwartz, Professor of Neurobiology, University of Pittsburgh
A better understanding of neural population function would be an important advance in systems neuroscience. The change in emphasis from the single neuron to the neural ensemble has made it possible to extract high-fidelity information about movements that will occur in the near future. The realization that useful information is embedded in the population has spawned the current success of brain-controlled interfaces. Since multiple movement parameters are encoded simultaneously in the same population of neurons, we have been gradually increasing the degrees of freedom (DOF) that a subject can control through the interface. Currently, monkeys in our laboratory are using this interface to control a very realistic, prosthetic arm with a wrist and hand to grasp objects in different locations and orientations. This technology has now been extended to a paralyzed patient who cannot move any part of her body below her neck. Using a high-performance “modular prosthetic limb” she has been able to control 10 degrees-of-freedom simultaneously. The control of this artificial limb is intuitive and the movements are coordinated, graceful, and closely resemble natural arm and hand movement. This subject has been able to perform tasks of daily living – reaching to, grasping and manipulating objects as well as performing spontaneous acts such as self-feeding.
Friday 9 October 2015 à 11h30, Salle de conférence.
Rôle des variants d’histones dans l’épigénétique et la tumorigenèse
Ali Hamiche, équipe Chromatine et régulation épigénétique à l’IGBMC de Strasbourg
Thursday 1 October 2015 à 11h, Salle de conférence.