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.
Vendredi 3 février 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.
Vendredi 27 janvier 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
Vendredi 20 janvier 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.
Vendredi 13 janvier 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.
Mercredi 21 décembre 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
Vendredi 9 décembre 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.
Vendredi 2 décembre 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 neutotransmetteur.
Vendredi 25 novembre 2016 à 14h, Amphi Giroud.
la connectivité GABAergique des précurseurs d'oligodendrocytes durant le développement cortical
Vendredi 25 novembre 2016 à 14h, Amphi Lavoisier.
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.
Jeudi 24 novembre 2016 à 18h, Salle de conférence.
Des circuits hippocampiques non canoniques
Mercredi 9 novembre 2016 à 12h, Salle de conférence.
Understanding presynaptic function at nanometer resolution
Vitaly KLYACHKO, Washington University, Saint Louis
Mardi 8 novembre 2016 à 11h, Salle de conférence.
The Chemical Biology of Epigenetic DNA and RNA base Modifications
Prof Thomas Carell, Ludwig-Maximillians University, Munich, Germany
Lundi 7 novembre 2016 à 11h, Salle de conférence.
Etude mécanistique et physiologique du transporteur lysosomal d’acides aminés PQLC2
Lundi 7 novembre 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
Vendredi 4 novembre 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)
Jeudi 20 octobre 2016 à 11h, Salle de conférence.
What good are dendritic spines - a voltage-imaging study
Dejan, Zecevic, Yale University (Dept C/M Physiology)
Mercredi 12 octobre 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.
Mardi 11 octobre 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
Vendredi 7 octobre 2016 à 11h30, Salle de conférence.
In vitro evolution of modified DNA enzymes
Marcel Hollenstein, CNRS UMR3523, I. Pasteur, Paris
Vendredi 7 octobre 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
Vendredi 30 septembre 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
Vendredi 23 septembre 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).
Lundi 19 septembre 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.
Vendredi 16 septembre 2016 à 11h30, Salle de conférence.
The inhibitory microcircuit in mouse presubiculum: from interneuron properties to input-output connectivity
Vendredi 16 septembre 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.
Jeudi 15 septembre 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.
Mardi 13 septembre 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
Vendredi 9 septembre 2016 à 11h30, Salle de conférence.
Lewis base catalysis of asymmetric acylation, sulfonylation and phosphorylation processes
Pr. Alan C Spivey (Imperial College, London)
Lundi 11 juillet 2016 à 11h, Salle de conférence.
Valorisation de la Recherche Publique
Lydie Viatte, Chef de projet en Santé, SATT IdF Innov
Jeudi 7 juillet 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
Jeudi 30 juin 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
Mercredi 29 juin 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
Lundi 27 juin 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.
Vendredi 24 juin 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.
Vendredi 24 juin 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.
Vendredi 17 juin 2016 à 11h30, Salle de conférence.
Development and use of chemical tools to modulate gene expression in cancer cells
Paola Arimondo (ETaC, Toulouse)
Jeudi 16 juin 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
Mercredi 15 juin 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
Vendredi 10 juin 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
Jeudi 9 juin 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.
Mardi 7 juin 2016 à 11h, Amphi Lavoisier.
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
Mardi 7 juin 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
Vendredi 3 juin 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
Vendredi 27 mai 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.
Vendredi 20 mai 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.
Vendredi 20 mai 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
Mardi 17 mai 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.
Vendredi 13 mai 2016 à 11h30, Salle de conférence.
Neuronal circuits for dynamic auditory processing and learning
Maria Geffen, University of Pennsylvania
Lundi 9 mai 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
Vendredi 22 avril 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)
Vendredi 22 avril 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
Vendredi 15 avril 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)
Jeudi 14 avril 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
Lundi 4 avril 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
Jeudi 31 mars 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
Vendredi 25 mars 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
Lundi 21 mars 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
Vendredi 18 mars 2016 à 13h30, Salle de conférence.
Functions of Scaffold Protein Rapsyn in Clustering nAChRs and Positioning Lysosomes
Professor Mohammed Akaaboune, University of Michigan
Lundi 14 mars 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
Vendredi 11 mars 2016 à 11h30, Salle de conférence.
MicroARNs et maladie d'Alzheimer: mécanismes moléculaires, facteurs de risque, diagnostic et traitement
Sébastien Hebert (Université Laval, Québec)
Vendredi 11 mars 2016 à 14h, Salle des Thèses.
Healthy aging by muscle mitochondrial stress adaptation?
Susanne Klaus (German Institute of Human Nutrition, Potsdam, Allemagne)
Jeudi 10 mars 2016 à 11h, Salle de conférence.
The Biology of axonal and synaptic Power Supplies
Timothy RYAN (Cornell University, New York)
Jeudi 10 mars 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
Vendredi 19 février 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.
Vendredi 5 février 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)
Jeudi 4 février 2016 à 11h, Salle de conférence.
Journée interdisciplinaire UFRs Math-info et Biomédicale
Christine Graffigne et Charbel Massaad
Vendredi 22 janvier 2016 à 9h, Salle de conférence.
Instabilité posturale chez les seniors : dysfonction vestibulaire périphérique ou centrale ?
Elodie CHIAROVANO, UMR8257 COGNAC G
Vendredi 22 janvier 2016 à 14h30, Salle des Thèses.
Advanced optical methods for fast and three-dimensional control of neural activity
Vendredi 22 janvier 2016 à 14h, Salle de conférence.
Blunting the Spinal Muscular Atrophy Disease phenotype in a C. elegans model system
Jeudi 21 janvier 2016 à 11h, Salle des Thèses.
Nouvelle approche neuroprotectrice et remyélinisante par l’étazolate dans le système nerveux central : Implication des α-sécrétases (ADAM10)
Mercredi 20 janvier 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.
Vendredi 18 décembre 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.
Vendredi 18 décembre 2015 à 13h30, Salle de conférence.
Learning and memory in amygdala circuits
Andreas Lüthi, Friedrich Miescher Institute for Biomedical Research, Basel
Vendredi 18 décembre 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.
Jeudi 17 décembre 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.
Vendredi 11 décembre 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).
Jeudi 10 décembre 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.
Vendredi 4 décembre 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.
Mercredi 2 décembre 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)
Vendredi 27 novembre 2015 à 10h, Salle des Thèses.
Understanding HIV transcription : Implications for HIV Cure
Monsef Benkirane, Institut de Génétique Humaine (IGH) de Montpellier
Jeudi 26 novembre 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
Mercredi 25 novembre 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.
Vendredi 20 novembre 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)
Vendredi 20 novembre 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
Jeudi 19 novembre 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
Lundi 9 novembre 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).
Jeudi 5 novembre 2015 à 18h, Salle de conférence.
Plate-Forme Cochin Imagerie, de la molécule à l’organe
Pierre Bourdonne, Plate-Forme Cochin Imagerie
Vendredi 16 octobre 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
Vendredi 16 octobre 2015 à 13h30, Salle de conférence.
Autophagy and plasma membrane domains
Patrice Codogno, Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253
Mercredi 14 octobre 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.
Vendredi 9 octobre 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
Jeudi 1 octobre 2015 à 11h, Salle de conférence.
Tools for Analyzing and Repairing Complex Biological Systems
Ed Boyden, MIT Center for Neurobiological Engineering, Massachusetts Institute of Technology
To enable the understanding and repair of complex biological systems such as the brain, we are creating tools that enable molecular-resolution maps of large scale systems, as well as technologies for observing and controlling high-speed physiological dynamics in such systems. First, we have developed a method for imaging large 3-D specimens with nanoscale precision, by embedding them in a swellable polymer, which upon exposure to water expands isotropically severalfold. This method, which we call expansion microscopy, enables conventional diffraction-limited microscopes to do large-volume nanoscopy. Second, we have collaboratively developed strategies to image fast physiological processes in 3-D with millisecond precision, and used them to acquire neural activity maps throughout small organisms. Third, we have collaboratively developed nanotechnological and robotic methods to record high-speed electrical events with single cell resolution in living mammalian brain. Finally, we have developed a set of genetically-encoded reagents, known as optogenetic tools, that when expressed in specific neurons, enable their electrical activities to be precisely driven or silenced in response to millisecond timescale pulses of light. In this way we aim to enable the systematic mapping, dynamical observation, and control of complex biological systems like the brain.
Vendredi 25 septembre 2015 à 11h30, Salle de conférence.
The tumour suppressor PML, Cancer Stem Cells and Tumour Progression.
Tarik Regad,The John van Geest Cancer Research Centre, Nottingham Trent University
Mercredi 23 septembre 2015 à 11h, Salle de conférence.
BIOSENSORS TO PROBE CENTRAL NERVOUS SYSTEM CELL SIGNALING AND FUNCTION
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. Niko Hildebrandt and Dr. Pierre Vincent), and 1 talk delivered by a talented Ph.D. student (Alice Louail). The format of the ENP seminars of the season 2015-2016 will try to balance the representation of women and men among the invited speakers.
Jeudi 17 septembre 2015 à 18h, Salle de conférence.
Autophagy and Parkinson’s disease: pathophysiology and therapeutic approaches
Erwan Bézard Institut des Maladies Neurodégénératives Université de Bordeaux, CNRS UMR 5293
Mercredi 16 septembre 2015 à 10h30, Salle de conférence.
Choix versus addiction dans les modèles animaux d’addiction aux drogues
Mercredi 15 juillet 2015 à 13h, Salle des Thèses.
“All free radicals are not created equal”: Drugs, electron transfer reactions, and toxicological implications
Pr Arno Siraki (Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB Canada)
Mardi 7 juillet 2015 à 11h, Salle de conférence.
Structural Insight into MLL family Histone Methyltransferases
Pr Ming Lei, Directeur adjoint de l'Institut des Sciences Biologiques à Shanghai, Chine
Jeudi 2 juillet 2015 à 14h30, Salle de conférence.
Exploiter les secrets de l'immunopeptidome du CMH I dans le développement d'immunothérapie personnalisée du cancer
Pr Pierre Thibault, Université de Montréal, Canada
Mercredi 1 juillet 2015 à 11h, Salle de conférence.
Role of vesicular trafficking in membrane microdomains and protein targeting at the synapse
Mercredi 24 juin 2015 à 13h, Salle de conférence.
Investigating the pathophysiology of Amyotrophic Lateral Sclerosis using human induced pluripotent stem cell technology
Gareth Miles, University of Saint Andrews
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which a greater understanding of early disease mechanisms is needed to reveal novel theraputic targets. We are therefore investigating the pathophysiology of ALS using human induced pluripotent stem cell (iPSCs) technology. Utilising whole-cell patch-clamp recordings we have revealed a dysfunctional phenotype in MNs derived from iPSCs of ALS patients (harbouring TARDBP or C9ORF72 mutations). This phenotype is characterised by an initial period of hyperexcitability followed by a progressive loss of voltage-activated currents and action potential output. We are currently investigating the potential role of perturbed glial-neuronal interactions in these pathological changes. Our findings to date implicate early dysfunction or loss of ion channels as a convergent point that may contribute to the initiation of downstream degenerative pathways in ALS and highlight the importance of addressing MN function, perhaps by targeting ion channels, when designing new treatment strategies for ALS. In addition, the sensitive but robust pathophysiological phenotype we have revealed in this human MN-based model provides an invaluable tool for the screening of emerging ALS therapeutics.
Vendredi 19 juin 2015 à 11h30, Salle de conférence.
La vidéo du séminaire
Pain and the Brain: Fears and Phantoms
Nicholas Rawlins, University College Oxford
Chronic pain is a serious clinical issue in humans. It seems clear that the problems of chronic pain patients derive not only from the experience of pain itself, but also from the anticipation of further pain at some point in the future. For many years, animal studies offered the only way to identify the brain structures and neurochemicals that underpin anticipatory fear or anxiety. I will describe how it proved possible to apply findings from studies of animal learning to design new functional imaging paradigms identifying the separate brain structures involved in the experience and the anticipation of pain in humans. Such paradigms enable us to visualise the separate brain circuits underlying the experience of pain and the anticipation of pain. Treatment with anxiolytic drugs reduces activation in the anticipatory circuit, but leaves activity in the experiential circuit unchanged. Inducing an expectation that an impending stimulus may be particularly painful enhances perceived pain intensities, through a circuitry which differs from that recruited when painful stimulus intensities themselves are increased. These kinds of studies may provide new ways to develop and evaluate treatments – whether pharmacological or psychological – that are intended to ameliorate the problems of chronic pain sufferers. Finally, I will describe new experimental work on phantom limb pain which suggests ways in which this classically intractable condition might be ameliorated.
Vendredi 5 juin 2015 à 11h30, Salle de conférence.
La vidéo du séminaire
Neuronal diversity in development and diseases: a human pluripotent stem cell perspective
Stéphane NEDELEC, ISTEM, INSERM UMR 861
Mercredi 27 mai 2015 à 13h, Salle de conférence.
Genetic analysis of cholinergic regulation of cognitive function
Marco Prado, Robarts Research Institute, U Western Ontario
In this talk I will summarize efforts to understand long-term regulation of brain functions by distinct groups of cholinergic neurons. By using conditional knockout mice coupled to next generation sequencing as well as neurochemical and molecular tools, I will discuss how cholinergic neurons can fine-tune circuitries in the brain by a myriad of different mechanisms. By combining genetics, including chemogenetic tools, and behavioral assessment using touchscreen technology it is now feasible to dissect how specific cholinergic circuits regulate executive functions, such as attention and cognitive flexibility, as well as hippocampal-dependent learning and memory.
Vendredi 22 mai 2015 à 11h30, Salle de conférence.
La vidéo du séminaire
Biphotonic molecules in the service of biology or defense
Chantal Arnaud (ENS-Lyon)
Biphotonic light absorption spans different fields of applications from biology and therapy to defense. The design of chromophores for these applications is strongly related to excited state properties of molecules. During this seminar, our molecular engineering work will be presented in the view of biological imaging, singlet oxygen generation for photodynamic therapy and optical power limiting. Besides the molecular design, the compatibility of molecules with their environment will be addressed for each applications.
Vendredi 22 mai 2015 à 13h30, Salle de conférence.
Journée Enseignement Interactif
Animée par le Groupe de Travail Enseignement de la SFBBM
Jeudi 21 mai 2015 à 10h - 17h, Amphi Weiss.
Bio-orthogonal and bio-specific bond-forming reactions for manipulation of biomolecules
Alain Wagner, Labex MEDALIS - UMR 7199, Faculty of Pharmacy, Illkirch Graffenstaden
Jeudi 21 mai 2015 à 11h, Salle de conférence.
Time super-resolution microscopy - A rapid change in SNAP-25 precedes fusion on the millisecond time scale
Manfred Lindau, Cornell University and MPI fBC Göttingen
Jeudi 21 mai 2015 à 11h, Amphi Lavoisier.
Modélisation animale de l'addiction à l'alcool : de la neurobiologie à la recherche de nouveaux traitements
Mercredi 6 mai 2015 à 13h, Salle de conférence.
Leveraging Medical Big Data for Improved Clinical Decision Making
Dr. Daniel L. Rubin, Stanford University, School of Medicine, USA
Our research group uses computational methods to leverage the information in radiology images to enable biomedical discovery and to guide physicians in personalized care. Just as biology has been revolutionized by online genetic data, our goal is to advance radiology by making the content in images computable and to electronically correlate images with other clinical data such as pathology and molecular data. Our work develops and translates basic biomedical informatics methods to improve radiology practice and decision making in several areas: tools to efficiently and thoroughly capture the semantic terms radiologists use to describe lesions; standardized terminologies to enable radiologists to describe lesions comprehensively and consistently; image processing methods to characterize the shape of lesions; content-based image retrieval with structured image information to enable radiologists to find similar images; methods to enable physicians to quantitatively and reproducibly assess tumor burden in images and to more effectively monitor treatment response in cancer treatment; natural language techniques to enable uniform indexing, searching, and retrieval of radiology information resources such as radiology reports; and decision support applications that relate radiology findings to diagnoses to improve diagnostic accuracy.
Vendredi 24 avril 2015 à 13h30, Salle de conférence.
The physiological synergistic activation of dendriticvoltage-gated calcium channels
Marco Canepari, Laboratoire Interdisciplinaire de Physique, UMR5588, Grenoble, France
At pyramidal neurons, action potentials generated in the axon hillock back-propagate into the dendrites activating different types of voltage-gated Ca^2+ channels (VGCCs). The consequent Ca^2+ signal represents a precise code for the dendritic sites where the cell receives synaptic inputs and plays itself a role in the propagation of electrical signals within the dendrites. Using a recently developed optical technique (Jaafari et al. 2014) we investigated in detail the activation of dendritic VGCCs during physiological action potentials. All types of high-voltage activated (HVA) VGCCs (L-type, N-type and P/Q type) contribute to the kinetics of action potentials, in particular by activating K^+ channels. The longer lasting action potential prolongs the duration of activation of low-voltage activated Ca^2+ channels (T-type). The result is a compensation of the loss of the Ca^2+ signal component mediated by LVA VGCCs with the larger component mediated by LVA VGCCs. Thus, functional coupling of VGCCs underlies the high-fidelity of fast dendritic Ca^2+ signals during individual action potentials which occur in the majority of dendritic field.
Vendredi 17 avril 2015 à 11h30, Amphi Lavoisier.
Inorganic Chemistry of Cellular Decision Making Processes : Metallome Changes in Normal and Pathological States
Prof. Thomas O'Halloran, Northwestern University, Evanston Il, USA
Jeudi 16 avril 2015 à 11h, Amphi Giroud.
Neurotransmitter Switching in the Adult Brain
Nick Spitzer, UC San Diego
The brain changes in response to changes in the environment and experience, and these changes underlie processes such as learning and memory. Substantial evidence demonstrates that this brain plasticity results from changes in the strength and number of synapses – the connections that neurons make. But is there more to it than that? The neurotransmitters made by neurons, which they use to signal to one another, have long been thought to be fixed and unchanging, and to be part of neuronal identity. Transmitter switching – substituting one neurotransmitter for another - is a relatively newly recognized form of plasticity. It occurs both during development and in the mature brain, it regulates behavior, and it may provide a basis for treating neurological disorders. We have visualized transmitter switching in single neurons in the adult brain and begun to understand the signaling cascade by which transmitter switching is achieved in the embryonic nervous system. These findings raise questions about the flexibility of the connectome and the involvement of transmitter switching in neurological disorders.
Vendredi 3 avril 2015 à 11h30, Salle de conférence.
La vidéo du séminaire
mTOR pathophysiology in senescence and rare diseases of growth and metabolism
Mario Pende, Institut Necker-Enfants Malades, INSERM U1151
Mercredi 1 avril 2015 à 10h30, Salle des Thèses.
SUMO as a signal for ubiquitin modification
Prof. Ron Hay, College of Life Sciences, University of Dundee (UK)
Jeudi 26 mars 2015 à 11h, Salle de conférence.
Protein S-Nitrosylation, Redox Stress, and NMDA Receptors in Alzheimer’s and Parkinson’s Diseases
Stuart Lipton, Sanford Burnham Medical Research
The relationship of misfolded proteins, as found in Alzheimer’s disease (AD) and Parkinson’s disease (PD), with excitotoxicity has remained obscure. Hyperactivation of extrasynaptic NMDA-type glutamate receptors (NMDARs) leads to excessive Ca influx and generation of free radicals, including nitric oxide (NO) and reactive oxygen species (ROS). Emerging evidence suggests a major role for protein S-nitrosylation (transfer of NO to a critical thiol group to regulate protein function via SNO-Protein formation). We found this reaction mimics the effect of rare genetic mutations that cause these diseases. One such affected molecule is protein-disulfide isomerase (PDI), an enzyme responsible for normal protein folding. Redox stress precipitates S-nitrosylation of PDI (forming SNO-PDI), leading to misfolded proteins, synaptic injury and neuronal death in AD, PD and amyotrophic lateral sclerosis (motor neuron disease). This discovery links protein misfolding to excitotoxicity and free radical formation. Another protein that is S-nitrosylated in AD and possibly other diseases is dynamin-related protein 1 (Drp1), a mitochondrial fission protein. We found that NO, produced in response to oligomeric beta-amyloid (Aß) peptide and resultant NMDAR hyperactivation, triggers excessive mitochondrial fission, synaptic loss, and neuronal damage via S-nitrosylation of Drp1- (forming SNO-Drp1). SNO-Drp1 is increased in brains of human AD patients and may thus contribute to the pathogenesis of neurodegeneration. Taken together, our findings suggest that aberrant nitrosylation events contribute to both protein misfolding and excessive mitochondrial fragmentation in neurodegenerative conditions, contributing to synaptic loss and neuronal cell death. We have also found that blockade of NMDAR activity can, in large measure, protect neurons from this type of injury, particularly if *U*ncompetitive, *F*ast *O*ff-rate (*UFO*)-type antagonists like memantine are employed because they block excessive extrasynaptic NMDAR activity without disrupting normal synaptic activity. The improved NMDAR antagonist, NitroMemantine, protects synapses far better than memantine and preserves hippocampal function on neurobehavioral testing of AD transgenic mouse models.
Vendredi 13 mars 2015 à 11h30, Salle de conférence.
Transient migrating neurons: organizers of cortical circuits
Alessandra Pierani, CNRS UMR7592 Université Paris Diderot
Our laboratory studies the role of transient populations of glutamatergic neurons in the development of the cerebral cortex. Using genetic tracing and cell ablation in the mouse we have characterized several populations of early-born neurons which have the common and unique characteristics to distribute over long distance from their generation site and to be transiently present during development. These neurons serve as organizers of cortical neural and vascular development by orchestrating in a non-cell-autonomous manner the radial and tangential growth of the embryonic cerebral cortex, axonal targeting and the formation of functional areas. We will discuss how the presence and disappearance of these neurons is crucial for cortical wiring in normal and pathological conditions.
Vendredi 6 mars 2015 à 11h30, Salle de conférence.
Les inhibiteurs de la télomérase modulent l’expression et la sécrétion de l’alphafetoprotéine : Études in vivo et in vitro
Georges Hilal (Directeur du Laboratoire Cancer et Métabolisme, Université Saint-Joseph, Beyrouth)
Mercredi 4 mars 2015 à 11h, Salle de conférence.
Beta- and Gamma-secretases: fascinating proteases in the membrane and relevant for Alzheimer disease
Bart de Stooper, VIB, Flanders, Belgium
Over the last decade important progress has been made towards the understanding of the molecular pathobiology of Alzheimer’s Disease. One of the major breakthroughs was the identification of presenilin and its crucial role in the γ-Secretase processing of APP and Notch. We will show in the current presentation that our knowledge on γ-Secretase function and regulation has dramatically progressed in the last years. We will explain how different γ-Secretase complexes have different biological roles, and that selectively targeting them could provide safer drugs. Also increasing insights into structure and function could lead to safer drugs, such as gamma-secretase modulators, but also drugs that specifically interfere with docking of specific substrates to the different γ-Secretases. Finally insight into the regulation of the γ-Secretase complex only starts to emerge, which also could open new opportunities for safer drugs. We will also present unpublished novel insights int o the function of the Beta-secretase or BACE-1, which is now the most favored drug target in Alzheimer disease. It is clear that also this enzyme is involved in important neurobiological phenomena and that the big issue is whether a therapeutic window can be established or not.
Vendredi 13 février 2015 à 11h30, Salle de conférence.
A Fiberscope for Spatially Selective Photoactivation and Functional Fluorescence Imaging in Freely-behaving mice.
Cathie Ventalon, CNRS UMR8197 - INSERM U1024 - Ecole Normale Supérieure
Despite evident advances made in the past few years, understanding the mechanisms governing information integration in the central nervous system remains a challenge. By providing numerous tools for perturbing and recording neural activity, optogenetics has shown great potential to advance these questions. To establish the links between specific spatiotemporal activity patterns and behaviors, optical methods should ideally provide simultaneous access to a group of neurons with single cell resolution in freely behaving animals. However, so far, optogenetic control of neural activity in freely behaving rodents has been performed with illumination volumes larger than 50µm on a side, yielding significant limitations with respect to spatial resolution. In addition, these approaches have yet been coupled with functional imaging. Here, we demonstrate, for the first time to our knowledge, photoactivation with near-cellular resolution in freely behaving mice. Photoactivation patterns are generated with computer-generated holography, and transmitted to the mouse using a fiber bundle coupled to a micro-objective. The optical system also includes a fluorescence imaging pathway to locate cells and record neuronal activity. Imaging is based on intensity modulation of a laser beam which provides easy switching between epifluorescence, structured illumination, and scanless multi-point confocal microscopy. We tested the system for photoactivation and calcium imaging in freely-behaving mice co-expressing GCaMP5-G and ChR2-tdTomato in cerebellar molecular layer interneurons. We demonstrated that the field of view remained stable during our acquisitions and that we could reliably elicit an increase in GCaMP5-G fluorescence signal by targeting a single soma with a 5µm diameter photoactivation spot. In addition, this somatic calcium signal vanished when the photoactivation spot was moved just 20µm away from the soma, thus demonstrating that cells could be photoactivated with near-cellular resolution in freely behaving mice.
Jeudi 12 février 2015 à 11h30, Salle des Thèses.
Wiring of the cerebellar cortex: role of the adhesion-GPCR BAI3 and its ligand, the complement protein C1QL1
Mercredi 11 février 2015 à 13h, Salle de conférence.
Neural Circuitry Underlying Autism in Tuberous Sclerosis
Mustafa Sahin, Children's Hospital Boston / Harvard
Accumulating evidence suggests that TSC patients have non-tuber abnormalities that contribute to the development of the neurological and behavioral phenotype. Using mouse models of TSC, work from our lab with our collaborators has started to shed light on the cellular and neural circuit abnormalities underlying the neurobehavioral problems. We have shown that TSC1/2 proteins regulate axon specification, guidance, myelination and regeneration. Recently, we generated a conditional knockout of Tsc1 only in cerebellar Purkinje cells. Mutant mice displayed autistic-like behaviors – social impairment, restrictive/repetitive behaviors, and abnormal vocalizations. Importantly, treatment of mutants with rapamycin prevented the development of these behavioral abnormalities. Taken together, these preclinical studies have lead to collaborative clinical biomarker and treatment trials that are currently ongoing.
Vendredi 6 février 2015 à 14h, Salle de conférence.
Inhibition vs excitation: subthreshold mechanisms regulating cerebellar cortical output in vivo.
Ian Duguid, University of Edinburgh
The cerebellum is important for the coordination and control of complex motor movements, balance, posture and locomotion. In order to play this vital role, the cerebellum – and in particular the spinocerebellum - continuously samples sensory feedback from the periphery and descending cortical information to generate output signals that precisely control muscle movements. The activity of Purkinje cells – which provide the sole output signal from the cerebellar cortex – is governed by the balance of feedforward excitation and inhibition. Although decades of work have provided us with an in-depth understanding of how excitatory and inhibitory synaptic input can influence the firing patterns of Purkinje cells, how these signals interact to produce behaviourally-relevant output spike patterns *in vivo* has not been fully explored. To address this issue, we performed patch-clamp recordings from cerebellar Purkinje cells (dendritic and somatic), molecular layer interneurons and cerebellar granule cells in lobule V of awake, head-restrained mice during self-paced, voluntary locomotion. By optogentically manipulating the balance between feedforward excitation and inhibition we have generated new insights into the subthreshold mechanisms that govern Purkinje cell spike output during motor behaviour.
Vendredi 30 janvier 2015 à 11h30, Salle de conférence.
Common proteolytic pathways reveal interplay between cellular prion protein and Alzheimer's disease
Frédéric Checler, IPMC, Nice, France
Alzheimer’s disease results from the cerebral accumulation of amyloid peptides that are generated from a transmembrane protein (APP) upon cleavages by a set of proteolytic activities referred to as secretases. Unlike APP, the cellular prion is a GPI-anchored protein, which was shown to undergo proteolysis by yet unknown proteases. In this seminar, we will discuss the nature of the proteolytic events taking place on cellular prion and we will report on novel functions of its catabolites that ultimately unraveled a molecular cross-talk between prion and Alzheimer’s disease pathology.
Vendredi 23 janvier 2015 à 11h30, Salle de conférence.
La vidéo du séminaire
Nanoparticules à luminescence persistante : synthèses, propriétés et applications en imagerie optique in vivo
Cyrille RICHARD, UTCBS, UMR 8258 CNRS
Notre laboratoire s’intéresse depuis plusieurs années à la conception et à l’utilisation de nouvelles sondes pour l’imagerie optique chez le petit animal. Certains nanocristaux peuvent se charger sous l’effet d’une excitation lumineuse et sont ensuite capables d’émettre de la lumière sur une période pouvant aller de quelques minutes à plusieurs heures. Cette propriété, appelée luminescence persistante, permet une détection optique à travers les tissus sans phénomène d’autofluorescence. Au cours de ce séminaire je présenterai les résultats pionniers obtenus par notre laboratoire avec la première génération de nanoparticules à luminescence persistante, détectable environ 1 heure in vivo puis je retracerai les différentes étapes qui nous ont permis de passer au matériau intermédiaire, visible 5 fois plus longtemps pour enfin arriver au matériau de dernière génération, ré-excitable in situ, ce qui nous permet d’envisager des applications en imagerie optique in vivo sans contrainte de temps.
Vendredi 16 janvier 2015 à 13h30, Salle de conférence.
Use of micro prisms for imaging morphology and activity in neocortical columns
Dr. Robert Sachdev, Humboldt University, Berlin, Germany
One of the limitations of 2-photon imaging is that imaging is typically performed in single tangential planes.Micro prisms overcome this problem by imaging in single Z-axis planes. I will talk about the use of implanted prisms for imaging cortical structure and function in an entire column.I will talk about our current and ongoing developments: i.e. imaging from cortex and striatum or cortex and subcortical structures, and imaging activity in inputs (axons) and dendrites simultaneously
Lundi 15 décembre 2014 à 14h, Salle de conférence.
titre à venir
David McCormick, Yale School of Medicine
Vendredi 12 décembre 2014 à 11h30, Salle des Thèses.
Generating and shaping novel action repertoires
Rui Costa, Champalimaud Center for the Unknown, Lisbon, Portugal
Some actions are innate or prewired (such as swallowing or breathing). Others are learned anew throughout life, likely through a process of trial and feedback. We used electrophysiology, imaging and optogenetics in behaving animals to understand how novel self-paced actions are generated, and how specific actions that lead to particular outcomes are then selected. We uncovered that dopamine is critical for the generation of novel actions, and that plasticity in cortico-basal ganglia circuits is necessary for action selection. Furthermore, as actions are shaped they become organized into chunks, and neural substrates of parsing and concatenation of motor chunks emerge in basal ganglia circuits.
Vendredi 5 décembre 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
Gates and Ways of HIV entry
Fernando Arenzana Seisdedos (Institut Pasteur, Paris)
Jeudi 4 décembre 2014 à 11h, Salle de conférence.
From Receptors to Pain: The Molecular Dynamics of Pain
Mike Salter, University of Toronto
Neuron-microglial interactions are increasingly recognized as being key for physiological and pathological processes in the central nervous system. Microglia have been found to play a causal role in neuropathic pain behaviours resulting from peripheral nerve injury, and a core neuron-microglia-neuron signaling pathway has been elucidated. Within the dorsal horn, microglia suppress neuronal inhibition by a cascade involving activation of microglial P2X4 receptors causing the release of brain derived neurotrophic factor (BDNF). BDNF acts on trkB receptors which leads to a rise in intracellular chloride concentration in dorsal horn nociceptive output neurons, transforming the response properties of these neurons. In addition to suppressing inhibition, peripheral nerve injury causes activity-dependent facilitation at dorsal horn glutamatergic synapses which enhances nociceptive transmission. This enhancement is mediated by intracellular signaling networks involving serine/threonine and tyrosine kinases within nociceptive transmission neurons. Key for this enhancement is facilitation of NMDA receptor function by Src family tyrosine kinases. Recently we have discovered that microglia-to-neuron signaling is not only critical for pain hypersensitivity after peripheral nerve injury but also for the paradoxical hyperalgesic effect of morphine and other opioids. We anticipate that by targeting microglia-neuron signaling pathways new therapeutic strategies for chronic pain as well as its comorbid sequelae may be developed.
Vendredi 28 novembre 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
Heat shock protein 90 regulates HIV-1 gene expression and latency
Ariberto Fassati (University College London, GB)
Jeudi 27 novembre 2014 à 11h, Salle de conférence.
Nanostructure of active zones at the calyx of Held: New avenues paved by STED, dSTORM and resin-free scanning-electron-microscopy
Thomas Kuner, University of Heidelberg
The 3D arrangement of presynaptic active zone proteins is a key determinant in generating presynaptic function. Despite knowing the molecular identity of almost all presynaptic proteins, very little is known about the 3D positioning and stoichiometry of active zone proteins. The lecture will present our attempts of using superresolution microscopy (STED and 3D-dSTORM) to visualize vesicle proteins, active zone proteins and cytoskeleton at the calyx of Held giant synapse in fixed tissue samples. An fresh perspective on cellular ultrastructure will be introduced with our novel resin-free scanning-electron-microscopy (RF-SEM) approach combined with focused-ion beam SEM and electron tomography. These approaches confer unprecedented 3D views of ultrastructural organization from presynaptic nerve terminals to entire cells
Vendredi 21 novembre 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
Immunité innée et interactions virus-hôte autour des virus Bluetongue et Schmallenberg : histoires différentes et destins croisés
Damien Vitour (UMR1161 Virologie, ANSES-INRA-ENVA, MAISONS-ALFORT)
Mercredi 12 novembre 2014 à 11h, Salle de conférence.
From prion diseases to Alzheimer's disease: PDK1, a common therapeutic target
Benoit Schneider, Université Paris Descartes - INSERM UMR-S1124
Mercredi 5 novembre 2014 à 10h30, Bibliothèque de physique.
Synaptic sensing and modulation by microglia: A role in neurodegeneration?
Microglia, the immune glia of the brain, are known to be dynamic cells constantly surveying the health of the surrounding tissue and responding to damage with rapid process extension. In addition microglia processes are responsible for pruning synapses via a mechanism requiring complement receptor 3 (CR3). I will present work describing how microglia detect the activation of NMDA receptors in neurons via the intermediate release of ATP. In addition I will describe how microglia CR3 activation and ROS generation is a novel trigger for long term depression of synaptic activity when combined with tissue hypoxia. These data suggest how microglia dysfunction could contribute to synaptic impairment during neurodegeneration
Vendredi 24 octobre 2014 à 11h30, Salle de conférence.
The Chemistry of Oxygen Sensing in Humans and Other Animals
Prof. Chris Schofield, Head of Organic Chemistry, Chemistry Research Laboratory Université d'Oxford, GB
The lecture will describe studies aimed at identifying the chemical basis by which humans and other animals respond to changes in oxygen availability. It will describe how the discovery of a widespread oxygen sensing mechanism has opened up new pharmaceutical opportunities, and insights into how cells regulate gene expression
Jeudi 23 octobre 2014 à 11h, Salle de conférence.
The cerebellum and the rest of the brain, a story about loops?
Clement Lena, ENS Paris
Mardi 21 octobre 2014 à 10h30, Salle de conférence.
Sculpting the brain: activity-dependent mechanisms of neural circuit refinement
Karen Zito, University of California Davis
A fundamental goal in the field of developmental neurobiology is to understand how neural circuits are established during development and how they are refined by experience and altered in disease. Of particular interest are the circuits in the cerebral cortex, a part of the vertebrate brain with a central role in many higher order brain functions, including learning and memory, perception and cognition. Disorders in development of cortical circuits are thought to contribute to the etiology of many neurological diseases. Research in the Zito lab focuses on understanding the activity patterns and signaling mechanisms that drive the formation and loss of synaptic connections during experience-dependent modification of neural circuits and in disease. We use molecular genetic techniques and electrophyisological approaches combined with two-photon imaging technologies that enable both visualization and functional characterization of synaptic connections. I will discuss our latest progress in defining the neural activity-dependent mechanisms that drive structural plasticity of synaptic connections in the cerebral cortex
Vendredi 17 octobre 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
Réunion enseignement de Biochimie, Biologie Moléculaire, Génétique, Microbiologie
Groupe de Travail Enseignement (GTE) de la SFBBM
Chaque année voit l'apparition de nouvelles méthodes et de technologies de plus en plus précises et fines. Ceci conduit à la fois à une connaissance de plus en plus détaillée du fonctionnement global de la cellule et à la mise en évidence de l'extrême diversité des mécanismes retenus par l'évolution dans chaque grand groupe d'organismes du vivant. Ce flux constant d'une grande quantité d'information a un impact direct sur l'enseignement de la biologie: il nécessite un tri, une réflexion afin de poser deux grandes questions : - que faut-il enseigner ? - comment faut-il enseigner ? L'objectif de cette réunion d'enseignants-chercheurs et de chercheurs est d'initier une discussion sur la manière de sélectionner les points thématiques, leurs contours, leurs volumes respectifs, leurs distributions disciplinaires, face au flux d'information produit par les recherches en biologie. C'est une première approche qui doit permettre d'avancer des réponses à la question : que faut-il enseigner à nos étudiants ? Les 3 rapporteurs du GTE : Jean-Luc Souciet Université de Strasbourg Reynald Gillet, Université de Rennes 1 Norbert Latruffe, Université de Bourgogne
Jeudi 16 octobre 2014 à 13h, Amphi Weiss.
Cortical blood flow: From vascular networks to microstrokes and vasomotion
David Kleinfeld, University of California San Diego
What is the nature of the angioarchitecture in the cortex that allows the brain to meet the energy demands of neuronal computations? I will discuss the topology and geometry of cortical angioarchitecture, the implications of this angioarchitecture to the flow and distribution of blood, and the varied resilience and susceptibility of the vascular network and underlying neurons to blockages. I will conclude with a discussion of ongoing work on the nature of long-range correlations in the fluctuations of vascular diameter. An underlying theme of these studies is the development of new optical methods concurrent with scientific exploration
Vendredi 10 octobre 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
High resolution localization of voltage-dependent calcium channels and related proteins in CNS synapses
Ryuichi Shigemoto, I.S.T. Austria
Activation of the presynaptic voltage-dependent calcium channels (VDCCs) triggers vesicular release of neurotransmitters. The coupling distance between VDCCs and the vesicular Ca2+ sensor for release varies depending on types of VDCCs and synapses from loose to tight coupling. However, the precise localization of different types of VDCCs, as well as their related proteins involved in regulation of VDCC localization and function, has not been well known within the presynaptic zone (AZ) in axon terminals because of technical difficulties including lack of suitable antibodies for immunolabeling. Here, we used new VDCC antibodies coupled with preembedding and freeze-fracture replica immunogold labeling for VGCCs at the AZs of central mammalian synapses. Immunogold particles for P/Q- and N-type VDCCs showed small clusters within the AZ, whereas R-type VDCC was mainly distributed outside of AZ. Particles for RIM and Munc13-1 were concentrated at the AZ making small clusters and colocalized with Cav2.1, whereas CASK and Neurexin were distributed more diffusely in the AZ. SNARE proteins were distributed all over the presynaptic elements and not particularly concentrated in the AZ. To analyze potential modification of these distribution patterns accompanied with neuronal activity, we examined transgenic rats expressing channelrhodopsin-2 in cerebellar granule cells with 2-minute continuous light stimulation in vivo. We found that the number of Cav2.1 was reduced shortly after the stimulation in the AZ, increased at 30min and recovered to the control level within 4 hours. These changes in VDCC localization may contribute to the presynaptic plasticity by regulating the release probability and coupling distance.
Lundi 6 octobre 2014 à 11h30, Salle de conférence.
Evaluation du risque prion chez le primate : description d'une nouvelle pathologie médullaire
Mercredi 1 octobre 2014 à 13h, Salle de conférence.
Exploring general principles of neuronal circuits in a vertebrate brain
Dr. Minoru Koyama, Janelia Farm, Virginia, USA
Given the complexity of the nervous system, it is essential to find general principles of neuronal circuits for our understanding of the nervous system. Despite the accumulating knowledge in a wide variety of systems, it still remains elusive if there are such general principles. Previously we found a structural and functional ground plan that spans across diverse sensorimotor networks in hindbrain of larval zebrafish. This organization gives rise to a collection of cell types that exhibit particular structural and functional properties according to when and where a neuron is born. We started to characterize how these building blocks are used at synaptic, cellular and network level in functional circuits in hindbrain. In this talk, I am going to show you some evidence that these building blocks represent circuit motifs that perform particular computations across diverse networks in hindbrain
Lundi 29 septembre 2014 à 11h, Salle de conférence.
Attentional modulation of neuronal response gain and variability in alert monkey. New optogenetic techniques.
John Reynolds, Systems Neurobiology Laboratory, Salk Institute
Lundi 22 septembre 2014 à 11h, Salle de réunion LPP.
RLR- and TLR- mediated stimulation of human plasmacytoid dendritic cells by the yellow fever vaccine
Nolwenn Jouvenet, CNRS URA 3569, Département de Virologie, Institut Pasteur
Mercredi 17 septembre 2014 à 11h, Salle de conférence.
Spatial and temporal integration of cAMP/PKA signaling in neurons
Pierre VINCENT, Universite Pierre & Marie Curie, Paris
Mardi 8 juillet 2014 à 11h, Salle de conférence.
Burst-dependent plasticity driven by pre- synaptic NMDA receptors at the cerebellar PF-PC synapse
Mariano Casado, CNRS UMR8197/INSERM U1024 Paris
Vendredi 27 juin 2014 à 11h, Salle de conférence.
Tactile perception and working memory in humans and rats - psychophysics and neuronal mechanisms
Mathew Diamond, International School for Advanced Studies, Trieste, Italy
The Romo laboratory has shown that primates can store graded sensory stimuli in working memory for subsequent manipulation, but until now there is no demonstration of this capacity in rodents. Here we describe tactile working memory in rats - they compare two “noisy” vibrissal vibrations (termed “base” and “comparison”) separated by an inter stimulus interval. To set a standard against which to interpret rat capacities, humans performed the analogous task by comparing two vibratory stimuli on the fingertip. On average, the tactile acuity and working memory of rats is inferior to that of human subjects, but good rats perform better than humans. Thus, rats exploit a smaller and simpler brain to express unexpected cognitive capacities. We can gain insight into the underlying neuronal operations by recording activity during behavior. Neurons in sensory cortex show a clear coding of stimulus features. Neurons in downstream regions (prefrontal cortex, premotor cortex, hippocampus) are heterogenous; of particular interest are neurons that encode memory and those that compute the upcoming decision as the rat selects between complementary actions. A final understanding will require a systems approach, as we see that cortical regions become coherent in low frequency oscillation as they transfer information.
Vendredi 20 juin 2014 à 11h30, Salle de conférence.
Adventures with Sugars
Prof. Thisbe Lindhorst
Jeudi 19 juin 2014 à 11h, Salle de conférence.
Digital holography of metallic nanostructures
Mercredi 18 juin 2014 à 13h, Salle de conférence.
Molecular basis of myelin geometry in health and disease
Nicolas Tricaud, Institut de neurosciences de Montpellier
Lundi 16 juin 2014 à 14h, Salle de conférence.
What does the "arrow of time" stand for?
Etienne Klein, Laboratoire des Recherches sur les Sciences de la Matière, CEA
One hundred and thirty years after the work of Ludwig Boltzmann on the interpretation of the irreversibility of physical phenomena, and one century after Einstein's formulation of Special Relativity, we are still not sure what we mean when we talk of “time” or “arrow of time”. We shall show that one source of this difficulty is our tendency to confuse, at least verbally, time and becoming, that is the course of time and the arrow of time, two concepts that the formalisms of modern physics are careful to distinguish.
Vendredi 6 juin 2014 à 11h30, Salle de conférence.
Multicolor and multimodal nonlinear imaging of developing tissue
Emmanuel Beaurepaire, Ecole Polytechnique - CNRS - Inserm, Palaiseau
Modern issues in systems biology (neuroscience, development) require tissue-scale measurements of multiple cell parameters. Since its introduction in the early 90s, multiphoton (or nonlinear) fluorescence microscopy has proven invaluable for tissue studies with its ability to provide 3D sub-cellular resolution in thick/live samples. However multiparametric nonlinear imaging has until recently remained challenging. We will first illustrate how the combination of fluorescence with harmonics contrasts (SHG, THG) provides complementary information for applications such as early embryo imaging . We will then discuss advances in multicolor imaging. We report on a strategy that provides optimal and simultaneous two-photon excitation of three chromophores with distinct absorption spectra using two synchronized pulse trains . We report on volume and live multicolor imaging of 'Brainbow'-labeled tissues using this approach [2,3], opening the path to large-scale cell and lineage tracking. Finally, we will discuss the potential of additional advances such as wavefront control  and light-sheet excitation  to increase the imaging depth and speed of tissue imaging.
Vendredi 6 juin 2014 à 13h30, Amphi Giroud.
The structure and function of cortico-cortical connections
Leopoldo Petreanu, Champalimaud Centre for the Unknown, Lisboa, Portugal
The cerebral neocortex underlies human's unique cognitive abilities. Understanding how the neuronal circuits of the neocortex allows so many complex behaviors is one of the central challenges of neuroscience. Cortical areas are interlinked by an extensive network of long-range connections whose function is poorly understood. We recently developed optical methods that allow recording activity from specific long range projections in behaving animals as well as determining their connectivity. Using these novel techniques we are describing the basic wiring diagram of long-range connections linking distant cortical areas in the mouse brain. We are also characterizing the specific signals relayed across cortical areas in the context of different sensory tasks.
Jeudi 5 juin 2014 à 11h30, Amphi Giroud.
Stem-Cell Derived Models of Pain and ALS: A Physiological Approach
Brian Wainger, Harvard Univ & Boston Children Hospital
Lundi 26 mai 2014 à 11h, Salle H335.
Cytochrome P450 Steroid Oxidations: Some Answers and More Questions
Pr. F.P. Guengerich (Vanderbilt University, Nashville TN, USA)
Vendredi 23 mai 2014 à 9h30, Salle de réunion UMR8601.
Les voies d'acquisition du fer chez les bactéries et le transport d'antibiotiques (stratégie Cheval de Troie)
Dr Isabelle Schalk (UMR 7242 Biotechnologie et signalisation cellulaire-IREBS)
Vendredi 23 mai 2014 à 11h, Salle de réunion UMR8601.
Chimie de synthèse à l’interface avec la Biologie : quelques exemples
Boris Vauzeilles (Institut de Chimie des Substances Naturelles Gif-sur-Yvette)
L’application d’outils synthétiques à l’exploration de processus biologiques, et l’utilisation de systèmes biologiques comme source d’inspiration, ont été nos principaux axes de recherche au cours de ces dernières années. Cette conférence présentera une sélection de quelques-uns de nos travaux dans ces domaines, incluant le développement de molécules bioactives synthétiques pour des applications agrochimiques, l’exploitation de protéines afin de diriger la synthèse de leurs propres inhibiteurs, ainsi que l’application de la «click-chemistry» à l’assemblage rapide de différents objets d’intérêt (synthèse rapide de neoglycoconjugués, développement de nouvelles molécules bioactives, assemblage de dispositifs photoactifs bio-inspirés, et marquage de bactéries vivantes).
Vendredi 23 mai 2014 à 13h30, Salle de conférence.
Host proteins that inhibit early steps of HIV-1 infection: p21 and TRIM28
Awatef Allouch, Inserm U 1030, IGR, Villejuif
Jeudi 22 mai 2014 à 11h, Amphi Claude Bernard.
Contribution du complexe Neurotensine/récepteur de la neurotensine de haute affinité dans la progression tumorale
Mercredi 21 mai 2014 à 13h, Amphi Weiss.
Mouvement, l'essence de la vie: deconstructing the spinal circuits for locomotion
Martyn Goulding, Salk Institute
The seminar will outline recent work in our lab using cutting edge genetics to dissect key features of the spinal sensorimotor circuitry. Two aspects of sensorimotor control will be discussed: 1) The control of limb movements by inhibitory neurons that secure flexor-extensor motor actvity and 2) the transmission and gating of cutaneous sensory stimuli in which we identify a novel circuit in the spinal cord for touch.
Vendredi 16 mai 2014 à 11h30, Salle de conférence.
GPCRs targeting: mechanisms and roles in neuronal structure regulation
Mercredi 7 mai 2014 à 13h, Salle de conférence.
Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection
Caroline Goujon, King's College London School of Medicine
Jeudi 24 avril 2014 à 11h, Salle de conférence.
Neural, behavioral, and biomechanical approaches to vocal motor control and sensorimotor learning
Sam Sober, Emory University, Atlanta, Georgia
Our lab uses the songbird vocal control system to investigate how the brain generates behavior and learns from experience. The neural circuits governing the learning and production of song are easily accessible to measurement and manipulation, providing a rich system in which to study the interplay between sensory feedback, motor control, and neural plasticity. However, although much is known about both song behavior and the functional anatomy of the songbird brain, we know very little about how the brain uses sensory feedback signals to rewire the neural circuits driving vocal behavior. In my talk I will present studies that employ a range of behavioral and physiological techniques to investigate sensorimotor learning and vocal control. First, by developing a system for manipulating auditory experience in the singing bird, we have demonstrated that adult birds maintain vocal performance by a process of error correction and defined the computational rules governing vocal learning. Shifting the pitch (fundamental frequency) of auditory feedback leads to compensatory changes in the pitch of song. This result suggests that song is constantly evaluated relative to an auditory target and that the resulting error signals are used to correct vocal output. Furthermore, quantitative analysis of learning across conditions (error size, animal age) suggests that songbirds use the statistics of their prior sensorimotor experience to constrain their behavioral responses to sensory errors, reflecting a robust strategy for optimizing behavior. Second, neural recordings from premotor neurons in the songbird brain have revealed how these neurons contribute to the moment-by-moment control of vocal output. Third, studies using electromyographic (EMG) recordings, single-muscle electrical stimulation, and in vitro approaches allow us to quantify the mechanics of acoustic production. Together, these approaches allow us to investigate the relationship between vocal learning, the neural encoding of motor commands, and the transformation of neural activity into vocal behavior by the motor periphery.
Vendredi 18 avril 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
NEW ACTORS IN DIABETIC NEPHROPATHY: Pathways behind the scenes.
Asaad Eid, American University of Beyrouth et University of Texas Health Science Center at San Antonio
Mercredi 16 avril 2014 à 13h, Salle de conférence.
Metabolic Disruption by Flame Retardants: A Fat and Liver Story
Prof. Gale CAREY, University of New Hampshire
Mardi 8 avril 2014 à 11h, Salle de conférence.
Rationally Designing Novel Therapeutics for Duchenne Muscular Dystrophy: From Basic Science Discoveries to Pre-clinical and Clinical Studies
Bernard Jasmin, Faculté de Médecine de l'Université d'Ottawa
Mardi 8 avril 2014 à 11h30, Amphi Lavoisier.
Probabilistic models of sensorimotor control and decision making
Daniel Wolpert, University of Cambridge
The effortless ease with which humans move our arms, our eyes, even our lips when we speak masks the true complexity of the control processes involved. This is evident when we try to build machines to perform human control tasks. While computers can now beat grandmasters at chess, no computer can yet control a robot to manipulate a chess piece with the dexterity of a six-year-old child. I will review our work on how the humans learn to make skilled movements covering probabilistic models of learning, including Bayesian and structural learning. I will also review our recent work showing the intimate interactions between decision making and sensorimotor control processes. This includes the relation between vacillation and changes of mind in decision making and the bidirectional flow of information between elements of decision formations such as accumulated evidence and motor processes such as reflex gains. Taken together these studies show that probabilistic models play a fundamental role in human sensorimotor control.
Lundi 7 avril 2014 à 11h, Salle de réunion LPP.
Regulating Mitochondrial Movement and Clearance, and Why a Neuroscientist Cares
Tom Schwarz, Children's Hospital Boston
Mitochondria are highly dynamic organelles and the regulation of their movement determines their distribution within cells. The extraordinary architecture of neurons makes them particularly dependent on mitochondrial motility and particularly vulnerable if damaged mitochondria are not efficiently removed. The presentation will review the mechanism by which motor proteins are coupled to mitochondria and present three pathways that regulate mitochondrial dynamics: Ca2+, glucose, and mitochondrial depolarization. Each of these pathways, when misregulated, hold relevance to neurodegenerative disorders.
Vendredi 4 avril 2014 à 11h30, Salle de conférence.
La vidéo du séminaire
Energetic of membrane trafficking
Diana Zala, Curie Orsay.
Mercredi 2 avril 2014 à 10h30, Salle de réunion UMR8250.
Brain-wide and cell-type specific synchronization at the service of attention
Pascal Fries, Ernst Strüngmann Institute (ESI)
I will show that natural viewing induces very pronounced gamma-band synchronization in visual cortex. This early visual gamma synchronizes to higher areas only if it conveys attended stimuli. Attentional top-down control is mediated via beta-band synchronization. Top-down beta enhances bottom-up gamma. Across 28 pairs of simultaneously recorded visual areas, gamma mediates bottom-up and beta top-down influences. Finally, I will show how pyramidal cells and interneurons are differentially synchronized and affected by attention and by stimulus repetition.
Vendredi 21 mars 2014 à 11h30, Salle Lavoisier B.
The hippocampal CA2 region: From dendritic spikes to social memory
Steven Siegelbaum, Columbia University College of Physicians and Surgeons
The CA2 region of the hippocampus has received little attention since it was first identified in 1934. However, recent electrophysiological studies have found that CA2 neurons occupy a unique niche in the cortico-hippocampal circuit, mediating a powerful disynaptic connection linking cortical input to hippocampal output. We have now identified synaptic and dendritic mechanisms that help enable CA2 to drive hippocampal output. Morever by silencing CA2 neurons through a novel transgenic mouse line, we found that CA2 is essential for social memory, the ability of an animal to remember others of the same species.
Jeudi 20 mars 2014 à 10h30, Amphi Lavoisier.
Implications du AhR dans la régulation des gènes de la myéline périphérique.
Mercredi 19 mars 2014 à 13h, Salle de conférence.
Cannabinoid-induced rapid cytoskeletal remodeling shapes neuronal morphology and growth.
Zsolt Lenkei, ESPCI ParisTech
Mercredi 12 mars 2014 à 10h30, Salle des Thèses.
The Synapse Nanomap
Silvio Rizzoli, European Neuroscience Institute Göttingen
The mechanisms behind many cellular pathways are well understood, and their molecular players are becoming increasingly clear. However, it is still unclear how cellular pathways are organized in quantitative terms. How many molecules are involved in a given pathway? Do their numbers correlate in any fashion? We have addressed these issues by studying the organization of synaptic vesicle recycling, a pathway that has long served as a model for the general mechanisms of cellular trafficking. We used quantitative Western Blotting to measure the absolute copy numbers of 62 proteins totalling more than 40% of the synaptic protein weight, and we estimated their locations by super-resolution fluorescence imaging. We used mass spectrometry to estimate the abundance of a further ~1100 proteins. Together with electron microscopy measurements of synaptic morphology, these data allowed us to generate a model of the synapse showing both protein numbers and structures. We found that protein copy numbers varied over more than three orders of magnitude, from around 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones. The copy numbers of proteins involved in the same step of the vesicle recycling pathway correlated closely. This finding points to a hitherto unknown mechanism of regulation in cellular pathways.
Vendredi 7 mars 2014 à 11h30, Salle de conférence.
Developpement d'une methode de mecanique/dynamique moleculaire de deuxieme generation. Applications aux complexes d'inhibiteurs avec des cibles proteiques et nucleiques.
Nohad Gresh, UMR 8601 CNRS, Paris Descartes
Mercredi 5 mars 2014 à 13h, Salle de conférence.
Two Distinct Heme Degradation Enzymes: heme oxygenase and IsdG
Masao Ikeda-Saito, Université de Tohoku, Japon
Mercredi 5 mars 2014 à 11h, Salle des Thèses.
Contrôle naturel et induit de l'infection par le VIH-1
Gianfranco Pancino, Unité de Régulation des infections rétrovirales à l'Institut Pasteur
Mardi 4 mars 2014 à 11h, Salle de conférence.
Structural plasticity of hippocampal excitatory and inhibitory networks
Dominique Muller, Centre Médical Universitaire, Genève
Mardi 25 février 2014 à 10h30, Salle des Thèses.
Self-immolative spacers in prodrug/profluorophore strategies
Frédéric SCHMIDT (CNRS, UMR 176-Institut Curie)
Self-immolative spacers are currently used in prodrug strategies or for enzymatic cleavable probes. Our aim is to control the rate of release of a drug after activation of the prodrug. We designed a new strategy to get quantitative data on the kinetic parameters. The principle is based on a photoactivation step permitting the liberation of the spacer in the form of a free phenol, and subsequent liberation of the drug after the self-immolation step. On a model compound, various parameters were studied: the substituents of the spacer, its pKa, the nature of the leaving group. With a self-immolative spacer strategy, it is also possible to liberate quasi-simultaneously two compounds (a drug and a reporter) for the determination of the locally delivered concentration of active compounds in vivo. Syntheses and rate determinations will be presented.
Vendredi 31 janvier 2014 à 13h30, Salle de conférence.
Domaines Nucléaires PML et Infections Virales Persistantes. Le paradigme du Virus Herpès Simplex 1 ?
Dr Patrick Lomonte, Université Claude Bernard Lyon 1,CNRS-UMR5534
Mercredi 29 janvier 2014 à 11h, Salle de conférence.
Imaging cerebral cortex function with single-cell and single-action potential resolution
Tsai-Wen Chen, Janelia Farm
The cerebral cortex is a thin layer of brain surface tissue that underlies our ability to think, feel, and remember. It contains immensely diverse cell types connected in a highly specific manner, with nearby neurons often performing related but distinct functions. Understanding the logic of cortical computation requires probing defined circuit components during natural behavior. We have recently developed genetically encoded neuronal activity sensors that allow non-invasive optical measurement of neuronal activity /in vivo/ with high spatiotemporal resolution. This method can be used to measure large populations of neurons as well as the activation of tiny synaptic compartments. I will describe applications of this approach to dissect synaptic events underlying orientation tuning in the visual cortex. In addition, I will present our recent efforts to image memory related activity in defined frontal cortical neurons.
Lundi 6 janvier 2014 à 11h30, Salle des Thèses.
A role for FOXP2 in social reward signaling
Matthias Groszer, Institut du Fer à Moulin
Mercredi 18 décembre 2013 à 11h, Salle des Thèses.
Cerebellar disease : Pathomechanism(s) involved in the episodic ataxia type 2
Philippe Lory,Institut de génomique fonctionnelle, Montpellier
Jeudi 12 décembre 2013 à 17h, Salle des Thèses.
Genes, synapses and autism
Thomas Bourgeron, Institut Pasteur
The diagnosis of autism spectrum disorders (ASD) is based on impairments in reciprocal social communication, and repetitive behaviours, but beyond this unifying definition lies an extreme degree of clinical and genetic heterogeneity. Our previous studies pointed at one synaptic pathway associated with the condition. Among the causative genes, synaptic cell adhesion molecules (neuroligins and neurexins) and scaffolding proteins (SHANK) are crucial for synapse formation/maintenance as well as correct balance between inhibitory and excitatory synaptic currents. In parallel, we identified genetic mutations that disrupt the serotonin-N-acetylserotonin-melatonin signalling in a subset of patients. This pathway is known to have pleiotropic effects, which include the regulation of sleep-wake cycles and the modulation of synaptic circuits. In this presentation, I will discuss our recent results coming from human genetics and mouse models studies that shed new light on the inheritance of ASD and on the phenotypic consequences of carrying mutations in clock and synaptic related genes. Hopefully, this knowledge should improve the diagnosis, care and integration of patients with ASD.
Vendredi 6 décembre 2013 à 11h30, Salle des Thèses.
La vidéo du séminaire
The role of SMN in the sensory-motor circuit function: implications in the pathogenesis of Spinal Muscular Atrophy
Dr George Z. MENTIS, Columbia University
Jeudi 5 décembre 2013 à 11h, Salle des Thèses.
Synthesis and application of fluorescent amino acids and sugars in optical imaging
Joanne XIE (ENS Cachan, Laboratoire de Photophysique et de Photochimie Supra- et Macromoléculaires)
Fluorescence microscopy is a powerful tool for the visualization of cellular proteins to study protein-protein, or, protein-carbohydrate interactions. We developed a general method for the synthesis of amino acids, sugars and cyclodextrins incorporating different fluorophores. These multifunctional molecules can be conjugated to peptides / proteins and used as biochemical tools, or, as selective probes in imaging. Moreover, some of the synthesized fluorescence probes can monitor selectively ions such as Cu2+, Hg2+, Ni2+,F-, or, CN-.
Vendredi 29 novembre 2013 à 13h30, Salle des Thèses.
Trafficking and fusion of neuropeptide containing dense core vesicles in mammalian CNS neurons
Mattijs Verhage, Vrije Universiteit Amsterdam and VU Medical Center
The regulated secretion of chemical signals in the brain occurs principally from two organelles, synaptic vesicles and dense core vesicles (DCVs). DCVs contain a diverse collection of cargo, including many neuropeptides that trigger a multitude of modulatory effects with quite robust impact, for instance on memory, mood, pain, appetite or social behavior. However, many fundamental questions remain open on DCV trafficking and secretion. My lab has established new photonic approaches to quantitatively characterize DCV-trafficking and fusion of many cargo types in living mammalian CNS neurons with single vesicle resolution. In this lecture I will present our most recent findings using these approaches on DCV trafficking and secretion, the molecular factors involved and the cellular locations where DCV fusion occurs.
Vendredi 22 novembre 2013 à 11h30, Salle des Thèses.
Genome-wide expression profiling of human Lymphoblastoid Cell Lines (LCL) discover novel SSRI antidepressants response biomarkers
David Gurwitz, National Laboratory for the Genetics of Israeli populations, Université de Tel Aviv, Israel
Mardi 19 novembre 2013 à 13h30, Salle de réunion faculté.
Le Rôle des adipocytes péri-tumoraux dans la progression tumorale mammaire
Catherine Muller-Staumont, CNRS, Toulouse
Vendredi 8 novembre 2013 à 14h, Salle de réunion faculté.
Etude des flux sanguins dans le placenta humain-Impact sur les fonctions biologiques du trophoblaste
Edouard Lecarpentier, UMR767-I
Lundi 28 octobre 2013 à 12h30, Salle de réunion faculté.
Dissecting Synaptic and Circuitry Mechanisms of Psychiatric Disorders
Guoping Feng, Massachusetts Institute of Technology
Synaptic dysfunction has emerged as a key pathology in several psychiatric disorders. Recently, large scale human genetic studies have also identified hundreds of overlapping risk genes for schizophrenia, bipolar disorder and autism. Using mutant mice as a model system, Dr. Feng will present how different synaptic defects could affect the same circuit and lead to similar behavioral defects and how mutations of the same gene could affect different circuits and contribute to different disorders.
Vendredi 25 octobre 2013 à 11h30, Salle des Thèses.
La vidéo du séminaire
Cytometry in the European Project ACuteTox
Jose ENRIQUE O’CONNOR
José Enrique O'Connor est directeur du "Center for Cytometry and Cytomics, The University of Valencia" et du "Laboratory of Cytomics and Cytomics Core Facility", au Prince Felipe Research Center Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Valencia
Mardi 15 octobre 2013 à 11h, Salle Leduc.
Photoacoustic Tomography: Beat Optical Diffusion and Diffraction
Lihong Wang, Washington University
We develop photoacoustic tomography technologies for in vivo functional, metabolic, molecular, and histologic imaging by physically combining non-ionizing electromagnetic and ultrasonic waves. Broad applications include early-cancer detection and brain imaging. Unlike ionizing x-ray radiation, nonionizing electromagnetic waves—such as optical and radio waves—pose no health hazard and reveal new contrast mechanisms. Unfortunately, electromagnetic waves in the non-ionizing spectral region do not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution tomography based on non-ionizing electromagnetic waves alone—such as confocal microscopy, twophoton microscopy, and optical coherence tomography—is limited to superficial imaging within approximately one optical transport mean free path (~1 mm in the skin) of the surface of scattering tissue. Ultrasonic imaging, on the contrary, provides good image resolution but suffers strong speckle artifacts as well as poor contrast in early-stage tumors. Ultrasound-mediated imaging modalities that combine electromagnetic and ultrasonic waves can synergistically overcome the above limitations. The hybrid modalities provide relatively deep penetration at high ultrasonic resolution and yield speckle-free images with high electromagnetic contrast. In photoacoustic computed tomography, a pulsed broad laser beam illuminates the biological tissue to generate a small but rapid temperature rise, which leads to emission of ultrasonic waves due to thermoelastic expansion. The short-wavelength pulsed ultrasonic waves are then detected by unfocused ultrasonic transducers. High-resolution tomographic images of optical contrast are then formed through image reconstruction. Endogenous optical contrast can be used to quantify the concentration of total hemoglobin, the oxygen saturation of hemoglobin, and the concentration of melanin. Melanoma and other tumors have been imaged in vivo. Exogenous optical contrast can be used to provide molecular imaging and reporter gene imaging. In photoacoustic microscopy, a pulsed laser beam is focused into the biological tissue to generate ultrasonic waves, which are then detected with a focused ultrasonic transducer to form a depth resolved 1D image. Raster scanning yields 3D high-resolution tomographic images. Superdepths beyond the optical diffusion limit have been reached with high spatial resolution. Superresolution beyond the optical diffraction limit has also been achieved recently. The following skin image was acquired in vivo in a mouse using optical-resolution photoacoustic microscopy.
Vendredi 11 octobre 2013 à 11h30, Salle des Thèses.
La vidéo du séminaire
Exploring Short-term Synaptic Plasticity: Does Biophysics Help to Understand Synaptic Function
Erwin Neher, Max Planck Institute for Biological Chemistry
The Calyx of Held - a glutamatergic giant nerve terminal in the auditory pathway - is large enough, that presynaptic whole-cell recordings can be performed with excellent control over voltage and the ionic milieu. This allows one to perform a multitude of ‘biophysical’ studies, such as determination of release rates as a function of [Ca++] using caged-Ca, or estimation of the release-ready pool of vesicles and its dynamics. Here, I will summarize such studies and address the question, in how far this information is useful to predict the short-term plasticity features, as observed postsynaptically when stimulating the afferent fiber of an unperturbed Calyx. It turns out, that a precise description of short-termfacilitation and –depression, as well as of its recovery requires a model, which is substantially more complex, than anticipated.
Vendredi 4 octobre 2013 à 11h30, Amphi Weiss.
La vidéo du séminaire
Whole secretory granule and plasma membrane motions just before (and during) exocytosis
Dan Axelrod, Ann Arbor
The motion of whole secretory granules toward the plasma membrane in the moments before fusion, and the deformation of the plasma membrane during the fusion event itself, raise interesting mechanistic questions. Do granules speed up or slow down before diffusion? Are there specialized sites? What regulates the process? When and for how long does the membrane remain deformed? These questions are addressed by fluorescence techniques, most notably polarized TIRF, which is discussed in some theoretical detail.
Lundi 30 septembre 2013 à 14h, Salle de réunion U603.
Facteurs héritables du diabète de type 2: Est-ce que la génétique explique tout?
Stéphane Cauchi, UMR8199-IBL, Lille
Nous connaissons certains facteurs environnementaux qui peuvent augmenter la susceptibilité de développer un diabète de type 2, comme par exemple l’alimentation et la sédentarité. Cependant, nous sommes inégaux devant ces facteurs de risque : il existe des prédispositions individuelles, familiales et parfois ethniques qui vont rendre plus redoutables l'effet d'une nutrition déséquilibrée ou d'un manque d'activité physique. La présentation sera consacrée à la forme commune de diabète de type 2, dite polygénique. L’état de l’art sera présenté et les nouvelles pistes de recherche pouvant expliquer l'héritabilité manquante seront évoquées, comme par exemple, la recherche de variants rares, l’épigénétique ou les interactions gène-environnement.
Lundi 30 septembre 2013 à 11h30, Amphi Lavoisier.
Studying Large-Scale Brain Networks: Electrical Stimulation & Neural-Event-Triggered fMRI
Nikos Logothetis, Max Planck Institute for Biological Cybernetics Tübingen
The brain is "the" example of an adaptive, complex system. It is characterized by ultra-high structural complexity and massive connectivity, both of which change and evolve in response to experience. Information related to sensors and effectors is processed in both a parallel and a hierarchical fashion. The connectivity between different hierarchical levels is bidirectional, and its effectiveness is continuously controlled by specific associational and neuromodulatory centers. In the study of such systems one major problem is the adequate definition for an elementary operational unit (often called an "agent"), because any such module can be a complex system in its own right and may be recursively decomposed into other sets of units. A second difficulty arises from the synergistic organization of complex systems and of the brain in particular. Synergy here refers to the fact that the behavior of an integral, aggregate, whole system cannot be trivially reduced to, or predicted from, the components themselves. Localizing and comprehending the neural mechanisms underlying our cognitive capacities demands the combination of multimodal methodologies, i.e. it demands concurrent study of components and networks; one way of doing this, is to combine invasive methods which afford direct access to the brain’s electrical activity at the microcircuit level with global imaging technologies such as magnetic resonance imaging (MRI). In my talk, I'll discuss two such methodologies: Direct Electrical Stimulation and fMRI (DES-fMRI) and Neural-Event-Triggered fMRI (NET-fMRI).
Vendredi 27 septembre 2013 à 11h30, Salle des Thèses.
La vidéo du séminaire
Circuit mechanisms regulating adult neural stem cells and neurogenesis
Hongjun Song, Johns Hopkins University
Adult neurogenesis arises from neural stem cells within specialized niches. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural stem cell activation, neural progenitor proliferation to new neuron maturation, synaptic integration and survival. I will present our recent studies using slice electrophysiology, immunohistology, genetic lineage tracing and manipulation and optogenetics to identify a novel niche mechanism involving parvalbumin-expressing interneurons that couples local circuit activity to diametric regulation of two critical early sequential phases of adult hippocampal neurogenesis
Vendredi 20 septembre 2013 à 11h30, Salle des Thèses.
La vidéo du séminaire