Addiction, interoception and sex differences (NEED)

For decades, neurosciences research was exclusively on males with the assumption that biological processes are the same across sexes. This dogma created a huge gap in our understanding of behavioral and brain mechanisms in both sexes. Although the field proved that this dogma is not always true, it left an important question unanswered: Why males and females have different vulnerability to brain disorders? Drug addiction is among the disorders with the highest men/women prevalence ratio. While the prevalence is higher in men, the gap between men and women is narrowing highlighting that drug addiction affects both sexes. Clinical and preclinical…

Administration and Research management / Magendie

The Neurocentre Magendie has 5 common administrative services. These services ensure, on behalf of the research teams and the platforms, all the administrative tasks in relation with Inserm, the University of Bordeaux, as well as with its public and private partners.

Analytical chemistry

The Analytical Chemistry Platform (PCA) provides a support in analytical chemistry mainly through chromatography and mass spectrometry. This platform, unique in France, provides a range of state-of-the-art knowledge and equipment allowing the development of any project in Neurosciences involving cannabinoids, neurosteroids and some neurotransmitters such as the glutamate and GABA. These analyses can be performed within the scope of the department research projects, with outside partners or as services.

Anatomical exploration and histology

The Neurocentre Magendie’s Histology and Anatomical Exploration Platform is part of a pool of technical and human resources provided to support research. This platform is focused on preparations of biological samples for histology, immunohistology, and imaging, ie observation, acquisition and image processing with optical microscopy. For this, the platform is equipped with the necessary equipment for the preparation of frozen tissues, fixed or included in paraffin (1 cryostat, 2 vibratomes and a microtome) from cutting (from 2 to 50 microns) to staining. The 2 microscopes equipped with fluorescence (DAPI, GFP, CY3) allow a fast and quality observation, and acquisition. The…

Bioinformatics

Bioinformatics Platform is a common technical service of the Neurocentre Magendie, whose role is to work in interaction with all the teams and technical platforms. Missions Define and analyze IT tools needs Create and implement data analysis algorithms Design, develop, implement and maintain the most suitable solutions: databases (MySQL, Oracle …), programs (Perl, PHP, Python, Java, C ++, VBA, Matlab, Spike2 …), web applications (HTML5, CSS3, javaScript, jQuery, PureCSS …), servers (Windows 2008 R2, Linux) Ensure user support (assistance, training, updating of functionalities) Empowering tools created

BioProt (Biochemistry and biophysics of proteins)

The first mission of the platform is to provide and maintain high-performance equipment in terms of centrifugation, numerical analysis, protein production and purification and biomolecular interaction studies. The platform staff teaches and advises users on these different instruments. The ingenieeron of the facility also provides services with the management of part or all of a study project including the interpretation of the results.

Brain Nutrient Sensing and Cognitive Trajectory from Development to Aging (NutriMind)

The general objective of the NutriMind team is to understand how food-derived molecules including nutrients, micronutrients, odorant molecules and bioactive metabolites from the gut microbiota influence neuroimmune interactions and neuronal networks and affect cognitive, emotional and feeding behaviors. To understand the basics of brain nutrient-sensing, we apply translational and integrative approaches ranging from in vitro human and murine iPSC-derived neurons and microglia, ex/in vivo behavioral, electrophysiological, imaging, cellular and molecular approaches using nutritional and transgenic mice models, to human clinic by the collection of dietary supplemented human cohorts including molecular, cellular and cognitive evaluations. These knowledge aim at developing nutrient-based…

Cell biology

The strong need for the production of primary cultured cells, recombinant proteins, plasmids and general molecular tools, calls for the reinforcement of some of those activities as a central resource of expertise. Many research groups at IINS have expertise in cell biology and have joined efforts to mutualize resources and optimize efficiency. In addition, many groups specialized in imaging, electrophysiology or behavior can benefit from access to an open resource in cell biology. IINS has thus created a common core service « Cell biology resource » that coordinates production of primary neuronal cultures, molecular biology tools and simple biochemistry. In addition, this…

Choice, Addiction and Neurodysfunctions (Candy)

Our research aims at identifying the psychological and neurobiological determinants of the different stages of addiction, drug choices and preferences in order to develop/improve strategies to prevent relapse. To successfully tackle these goals, we compare drug- versus nondrug-preferring rats to elucidate the psychological and neurobiological substrates underlying the abnormal preference for the drug. Our efforts are also concentrated in investigating the long-term preventive effects of a cue exposure procedure against relapse to reveal the brain regions that play a critical role in interoception, behavioral inhibition and motivation. Innovative techniques: in vivo recording, behavioral procedures for drug choices and preferences

Clinical and translational exploration of sensorineural hearing loss

Fundamental questions that are essential for efficient hearing rehabilitation are addressed: how do auditory hair cells synapses and central synaptic connections evolve with aging, sound trauma and genetic neuropathies? The molecular changes occurring in auditory synaptic transmission are deciphered in mouse models. Methods of viral gene transfer are developped in order to rescue and reverse the synaptic defects. Innovative techniques: cochlear viral gene transfer. gene editing. cochlear and hair cell electrophysiology.

Computational and systems neuroscience

Neocortical function and plasticity underlie the remarkable adaptive skills of mammals. Among different projects, our team is studying how the prefrontal cortex computes and adapts its strategies through experience and learning to optimally select the sequence of actions that is expected to produce the most beneficial outcome. We developed an entirely in vivo multidisciplinary approach combining electrophysiology and functional imaging (intrinsic and voltage-sensitive dyes imaging), multiphoton laser-scanning microscopy, gene transfer and optogenetic during behavior in head-fixed and freely-moving mice. Innovative techniques: in vivo patch-clamp and optogenetic, chronic two-photon imaging during behavior. decision-making in virtual reality. high-dimentional analysis of brain circuit

Computational Neuroscience

We study the combined roles of the amygdala, hippocampus and cortex in value prediction and interactions between fronto-basal loops in decision making and organisation of behavior. Innovative Techniques: Design of new algorithms of categorization, planning and natural language processing

Cortical plasticity

Our research topic is focused on the structure, function and dynamic regulation of cortical circuits in various conditions such as learning, development and disease. We investigate ion channel function in the different neuronal compartment to predict/analyse the coding properties of cortical neurons alone or in cell assembly. Using genetic models, we revealed the implication of ion channel dysfunctions in the hypersensitivity in response to sensory stimuli associated to neocortical hyperexcitability, features of fragile X syndrome and autism. We also study the anatomical connectivity of neocortical circuits and showed that its alterations named as a « connectopathy, » cause functional defects that may…

Decision and adaptation (DECAD)

The scope of our team is to understand the neurobehavioral mechanisms involved in decision-making. This work relies on sophisticated behavioural paradigms understanding the action-outcome relationships in goal-directed responses. The originality of our research is to integrate cognitive neuroscience and behavioural psychology in rodent trained in complex operant tasks. The use of pharmacological and genetic tools implemented by meta-analyses allows us to reveal the neural circuits underlying behavioural flexibility and adapted behaviour. We characterised functional thalamic nuclei and identified a maturation period of the dopamine meso-prefrontal system during adolescence that may explain some form of impulsive behaviour observed during this period.…

Development and Neurobiology of Neural Networks (DN3)

Our overall research objective is to decipher the neuronal basis of the short- and long-term functional plasticity of motor systems. In particular, we are characterising during embryonic development the synaptic and neuromodulatory properties of the preBötzinger complex neurons that drives respiratory oscillations. We also study the neuronal flexibility of respiration and locomotion oscillatory systems that function separately or spontaneously coordinate their action in given conditions (i.e. physical activity). The principal experimental goal of our work is to causally link cellular, synaptic and neural network physiology to particular aspects of adaptive behaviour. Innovative techniques: Electrophysiology, electrochemistry, dynamic clamp, calcium imaging, neuropharmacology,…

Developmental Brain Physiology and Pathology

A great challenge for our comprehension of brain development is to identify how biological signals (glutamate, monoamine, immune system, hormones) control the maturation of neuronal connections and brain circuit assemblies in healthy conditions as well as in psychotic disorders. In particular, we showed that the adaptation of developing excitatory synapses mainly depend on the dynamics of surface postsynaptic receptor, including the NMDA and AMPA receptor. Our team will combine cutting edge high resolution imaging and classical electrophysiological approaches to detect and decrypt the impact of auto-antibodies from psychotic patients. Innovative techniques: single-molecule imaging, receptor trafficking, ex vivo and in vivo…

Dopamine and neuronal assemblies

Our laboratory examines the functions of the « extended basal ganglia network », a neuronal network composed of interconnected limbic and motor nuclei. We aim at characterizing this network at the synaptic level, focusing on how synaptic transmission and plasticity are controlled by dopamine. Our research will provide new understandings of physiological functions (voluntary movements, associative learning…) and of dopamine-associated disorders (Parkinson’s disease, addiction…). Innovative techniques: in vivo and ex vivo electrophysiology, single-cell labeling, optogenetic, neuronal tracing, neuropharmacology and viral mediated gene deliver

Dynamic organization and function of synapses

Our team pursues a transdisciplinary approach, to study the interplay between the dynamics of the molecular components and the synaptic transmission. Based on advanced imaging techniques, we study AMPA receptors and its molecular partners. We obtained breakthrough data on nano-scale organization, dynamics and interaction of synaptic proteins and membrane trafficking, Our efforts are focused on the understanding of the synaptic components dynamics involved in higher cognitive functions and pathologies, such as Alzheimer disease. Innovative techniques | single particle tracking “PALM, STORM, STED”, live super resolution imaging, Patch-clamp

Dynamics of neuronal and non neuronal networks underlying memory processing (MEMORY)

Our team aims at elucidating the spatio-temporal evolution of memory traces and the cerebral vascular organization associated with memory, in health and disease. The team has made important breakthroughs in identifying early tagging of cortical networks required for the formation of enduring associative memory. We also identified molecular mechanisms involved in memory, including molecular tags and the interaction of CaMKII with NR2B receptors. Currently, our research mainly focuses on: 1- understanding the functional contributions of NMDA receptors subtypes and its molecular partners, 2- deciphering the role of the vascular networks in the stabilization of remote memories during the course of…

Ecological assessment and management of psychiatric disorders (ECOPSY)

The principal objective of our team is to combine advanced neuroimaging techniques and state-of-the-art mobile assessments of daily life behaviors, emotions and cognitive processes in order to understand the etiology and pathophysiology of CNS disorders. MRI allows for the characterization of neural networks involved in cognitive and emotional processes and their dysfunction, assessing the structural and functional integrity both of brain regions and the connections between regions of the brain network. Recent studies have also demonstrated the contribution of jointly using MRI and PET techniques, an approach which opens numerous new opportunities to identify structural and functional brain dysfunction and…

Emotion, Motivation and Cognition (EMOTIV)

Our research is interested in the interactions between emotions and cognitive processes in normal conditions and pathological states (short and long-stress, aging, disease, addiction…). Our main project aims at characterizing the neuronal substrates underlying the positive and negative emotion-memory interaction in normal young adult mice. We also study how the emotional impact on memory is altered by aging or in pathological states such as in Alzheimer’s disease, chronic alcohol and diencephalic dementia, to possibly restore the impaired memory functions. Innovative techniques: microdialysis, corticosterone assays, electrophysiology, rodent behavioural paradigms

Endocannabinoids and neuroadaptation

Our team aims at uncovering the functions of the endocannabinoid system in the brain as well as the cannabinoids regulation of behavior and psychotic disorders. By using conditional mutagenesis, we are currently dissecting the roles of cannabinoid receptors type-1 (CB1) in different cellular and subcellular localizations towards a better understanding of the general rules governing behavior such as memory, locomotor activity and olfaction. Innovative techniques : mitochondrial dynamic and function assessment, voltage-sensitive dye imaging (VSDI), in vivo & ex vivo electrophysiology, transgenic mice, in situ hybridization.

Energy balance and obesity

The main focus of our research is the understanding of the regulation of food intake and body weight. Our work is focused on the role of the mammalian target of rapamycin (mTOR), a cellular fuel sensor, and the endocannabinoid system (ECS) in controlling food intake and energy expenditure. We are identifying neuronal substrates and cellular mechanisms underlying the action of the mTOR pathway within the hypothalamus. We currently aim at understanding the relationship between cannabinoids type1 receptor (a molecular actor of the ECS) and mTORC1-dependent signaling in the control of neuronal circuits regulating food intake and body weight. Our work…

Genotyping

FR – La plateforme de génotypage du Neurocentre Magendie a été créée en janvier 2008 pour apporter une aide et libérer du temps aux équipes de recherche en leur proposant un service de génotypage. En effet, les modèles Transgéniques sont des outils devenus incontournables dans la recherche scientifique. L’utilisation de ces modèles requiert du temps, tant au niveau de la gestion des lignées, que dans l’identification du génotype de la descendance. Ces étapes sont pourtant indispensables pour constituer des groupes expérimentaux et sélectionner de nouveaux géniteurs en vue d’une production optimale. Au-delà du génotypage, la plateforme accompagne les équipes du…

Glia-neuron interactions

Our aim is to understand the biological bases of glia-neurons interactions in healthy and diseased nervous system (chronic pain, Alzheimer disease and multiple sclerosis). We showed the contribution of astrocyte to synaptic functions by showing the role of D-serine, a gliotransmitter released by astrocytes, in gating synaptic NMDA receptors and their dependent long-term plasticity. We are now also interested in analyzing fine morphological plasticity of astroglial cells as well as monitoring membrane trafficking of key proteins at the surface of astrocytes. Innovative techniques | In vitro electrophysiology, morphological analysis, MRI, chronic pain rat model

Hybrid sensorimotor performance

Our team uses hybrid systems, which mix biological control with artificial devices, in order to (i) increase our understanding of sensorimotor control and (ii) exploit this knowledge to restore and optimize movement. Instead of being pre-programmed in the brain, movement coordination largely depends upon multiple feedback loops that operate at different levels of the sensorimotor control system. For instance, muscle mechanics provides an instantaneous functional response to small perturbations, while segmental and transcortical reflexes are able to absorb increasingly larger perturbations by precisely coordinating muscle responses for the complex musculoskeletal design of our limbs. These loops are typically violated in…

IMN clinics

The clinical branch of the Institute of Neurodegenerative Diseases (IMNc) combines patient care (Expert Center for Parkinson’s disease, Dementia Clinic, French Reference Centre for Multiple System Atrophy, Competence Centre for Rare Dementia, Competence Centre for Tourette Syndrome) and clinical research in the fields of neurodegenerative diseases and movement disorders. Our research program builds on three axes. The first research axis investigates the pathophysiology of movement disorders and neurodegenerative diseases, focusing on dystonia, Tourette syndrome, gait, and tremor using both imaging and electrophysiological technics. The second research axis investigates the natural history of neurodegenerative disorders. It aims to determine factors of…

Mechanisms of Adaptive Processes in brain circuits (MAP)

The brain’s ability to constantly adapt its organization to ever-changing stimuli is termed « plasticity » and is a prominent feature of learning and memory in adults, as well as the assembly of neuronal circuits during critical developmental periods. Connections that convey relevant information and are the most active become stronger and stabilize, while less active ones weaken and eventually get eliminated, optimizing the storage and processing of information in the brain. Our research aims to examine the molecular and cellular mechanisms underlying these adaptive processes. We employ a multidisciplinary approach, including single-cell manipulation, electrophysiology, optogenetics, single-cell RNA sequencing, and high-resolution imaging,…

Mechanisms of neural circuit sensitivity to altered nutritional status (FoodCircus)

The objective of our team, in a perspective of healthy brain aging, is to better understand how unbalanced diets alter memory processes, and how specific micronutrients (vitamins, polyphenol) prevent memory decline in elderly. At the mechanistic level, the impact of nutritional status on glucocorticoid regulation is specifically studied knowing that glucocorticoids are critical for memory processes,and in metabolic response to nutrition. Innovative techniques: mitochondrial dynamic and function assessment, voltage-sensitive dye imaging (VSDI), in vivo & ex vivo electrophysiology, transgenic mice, in situ hybridization.

Membrane traffic at synapses (MemTraS)

Our goal in the team is to study the mechanisms regulating synapse function, focusing on membrane trafficking events in normal brain physiology or in the course of disease. We are interested mainly in the presynaptic element filled with synaptic vesicles fusing to release neurotransmitter molecules as well as the post-synaptic side where post-synaptic receptors are going through cycles of endocytosis and recycling, which is essential for synaptic transmission and plasticity. Finally, we are not only interested in canonical synapses, such as cortical glutamatergic synapses, but also in rare and much less understood synapse populations such as neuromodulatory dopamine synapses. To…

Microdissection

FR – Créée courant 2009 via un financement FRM, la plateforme de microdissection laser avait l’ambition d’offrir aux équipes du Neurocentre une technique de pointe permettant la réalisation de nouveau challenge scientifique. Ouverte uniquement aux équipes internes dans un premier temps, cette plateforme unique sur Bordeaux propose depuis 2012 ses services à toute la communauté scientifique et dans des thématiques différentes : cancérologie, culture cellulaire, études cliniques… La plateforme se fixe pour mission de vous accompagner dans la maitrise de l’appareil (formation, réglage du laser…) mais aussi dans les étapes primordiales de la préparation des échantillons à la microdissection laser…

Monoamines, Parkinson and Pain

Our research project aims to better understand the pathophysiology of Parkinson’s disease in order to improve the existing therapeutic approaches and to develop new therapies for the disease. Currently, we especially focus our work on the role of monoaminergic systems (noradrenaline, dopamine, serotonin) in the pathophysiology and therapy of Parkinson’s disease. The team is acknowledged for its neurochemical and electrophysiological inputs unraveling the mechanisms of action of the deep brain stimulation of the subthalamic nucleus and L-DOPA medication in animal models of Parkinson’s disease. Innovative techniques: multisite intracerebral microdialysis, motor and non-motor behaviors, in vivo electrophysiology.

Motoneurons and synaptic partners (MotoPSyn)

The objective of our team is to understand the mechanisms involved in the function of mammal spinal motor networks from its embryonic development to its pathological conditions, such as amyotrophic lateral sclerosis, ALS. In particular, we focus our efforts on: 1) deciphering the role of GABAergic interneuron in the genesis of spontaneous activity at early developmental stages and 2) identifying cellular and molecular mechanisms involved in the early motor deficits observed in spinal motoneurons from ALS mouse models. Innovative techniques | electrophysiology in vitro, ALS mouse models

Motor control and cognition

We explore the human capacity to plan different actions and form decisions from an abstract level (e.g number processing) to more concrete situation (e.g the ability to use tools). We also seek to understand the impact of mental effort and consecutive mental fatigue on these activities. Innovative techniques:  electrophysiology, pupillometry, transcranial magnetic stimulation. functional neuroimaging. computational models

Motricity analysis platform (PAM)

The Motion Analysis Platform (PAM) is dedicated to the analysis of motor skills and posture in humans and animals. It provides a set of complex and non-invasive tools for researchers and clinicians to analyse body movements (kinematic, kinetic, eyetracking…) as well as physiological data (electrophysiological measurements like EMG or EEG for instance).

Multimodal Translational Imaging

The PET research unit is a center dedicated to the molecular imaging with positron emitter tracers, created jointly in 2010 by the Hospital and the University of Bordeaux on the site of Xavier Arnozan hospital in Pessac. Since 2011, this unit is a core team of laboratory of excellence TRAIL. The centre, under the responsibility of Professor Philippe Fernandez, hosts a team of a dozen people from different departments and conducts imaging research in the CNRS laboratory INCIA (UMR 5287) directed by Jean-René Cazalets. Our expertise is based on participating to multicentric clinical trials promoted by academic structures (hospital, university)…

Network dynamics for procedural learning

Our objective is to unravel the neural mechanisms underlying cognitive and motor executive functions. Our main interests are the physiology of the planning, decision making, learning processes and their pathophysiological aspects such as dystonia and obsessive-compulsive disorder. We adopted a phylogenetic approach that drive us to address the question in a broad variety of vertebrates such as salamander, rodents, primates (both human and non-human) and songbirds in order to unravel the emerging complexity of the system studied along the evolution tree. We based our research on system level theoretical models validated by experimental data. Our experimental procedures range from optognetic…

Neural Basis of Perception

Attention and contextual knowledge are prerequisites for optimal perception and decision making. The overarching goal of our lab is to achieve a mechanistic neural framework for cognitive control and contextual modulation of perception and behavioral actions. Towards this goal, our team focuses on tactile sensation, one of the most predominant sensory modalities in rodents to perceive the world. We investigate how tactile inputs are processed and modulated in mouse somatosensory cortex and then gated to the downstream regions. We hypothesize a canonical mechanism of input integration and transformation into spike trains in individual pyramidal neurons at different brain states (e.g.,…

Neural circuits of anxiety

Fear can become elevated and continues in the absence of danger, becoming a psychiatric disorder called anxiety. Our research aims to highlight alterations in the neural circuits that control physiological fear in murine models of anxiety, through an analysis of connectivity, synaptic properties and gene expression profile. Our research is focused on insular cortex (insula) networks. This brain structure has been implicated in anxiety disorders by many functional imaging studies. We are also considering strategies to restore these alterations

NeuroDTx: Neuromodulation and Digital Therapeutics

Our team develops new neuromodulation paradigms and neuroprosthetic systems for repairing or replacing circuit-level functions that get disrupted after neurological disorders or injury. Our research combines techniques from Neuroscience and Neuroengineering, in particular in vivo electrophysiology, signal processing, machine learning and control engineering. Building upon previous experience of neuromodulation in the fields of epilepsy and spinal cord injury, we are now interested in expanding neuroprosthetic systems from motor to cognitive disorders. In particular, we aim at developing a large-scale brain network neuroprosthesis to restore memory after brain injury or neurodegenerative diseases such as Alzheimer’s disease. Our approach uses intracranial multielectrode…

Neurofunctional imaging group

We are a multidisciplinary research team gathering scientists from various domains: mathematics medical imaging, nuclear medicine, signal processing, psychiatry and cognitive neurosciences. Our scientific project ambitions at understanding the determinants of the development of brain networks underlying cognitive functions. In particular, we investigate the anatomo-functional, genetic and cognitive underpinnings of the human brain hemispheric specialization (HS). We recently designed and acquired the Brain Imaging Lateralization & GIN, a unique multimodal database in the world dedicated to the fundamental question of brain connectivity, in particular the roles of intra- and inter-hemispheric connectivity that underlie HS. Innovative techniques: in vivo human neuroimaging,…

Neurogenesis and pathophysiology

Role of adult born neurons in memory, Adult neurogenesis and cognitive aging, Ontogeny of the hippocampus and hippocampal-dependent functions, Role of actin regulators in developmental and adult neurogenesis, State of the art behavioral paradigms, Innovative Techniques: Optogenetic in behaving rodents, In utero and postnatal electroporation, Retrovirus labeling of adult-born neurons in vivo, Retrograde monosynaptic rabies viral tracing system

Neuronal circuits of associative learning

Our research is focused on the identification of the neuronal circuits and mechanisms mediating aversive associative learning. Using a combination of state of the art, behavioral, single unit and local field potential recrodings, optogenetic and anatomical tracing we aim to decipher the specific neuronal elements, circuits and mechanisms involved in the control of fear behavior and to understand how alteration sin such circuits promotes the development of pathological fear behavior. Innovative techniques: in vivo single unit and local field potential recordings, viral tracing approaches, optogenetic, associative behavior.

Neuroscience, Humanities & Society (NeHuS)

The NeHuS ‘Neuroscience, Humanities, and Society’ team aims at producing embedded Humanities and social sciences research in and on neuroscience within a neuroscience lab. This team intends to be useful to neuroscientists, as well as to the public understanding of neuroscience, through constant and close collaboration with neuroscientists. It is part of the movement to develop the philosophy in biology and, more generally, the organization of interdisciplinary research in and on the neurosciences based on a precise understanding of experimental practices, theoretical issues and methodological and conceptual questions encountered by neuroscientists in the pursuit of their research. The project of…

Nutribrain

As a technology transfer unit in Nutrition-Neuroscience backed by the NutriNeuro laboratory, the NutriBrain unit aims to structure a partnership research with food or food supplement companies for the development of products targeting brain function. NutriBrain allows responding optimally to the demands of companies by mobilizing and structuring the resources needed to carry out innovative projects.

Nutrition and Neuropsychiatric Symptom Dimensions (NutriPsy)

The aim of our research is to understand how Western-diet influences mood, well-being and cognition and can lead to neuropsychiatric disorders. As Western diet is characterized by low n-3 polyunsaturated fatty acid levels, we evaluate the role of lipid nutritional imbalance on brain remodeling, neuroimmune responses and emotional behavior. Innovative techniques | Lipid biochemistry, psychometric evaluation of behavior

Olfaction and memory

The ability to store and retrieve associations between specific sensory stimuli and behaviorally relevant information is a vital memory function: it allows the organism to adapt its behavior based on prior experience. Olfaction is a central sensory modality in rodents as it supports an array of crucial behaviors such as predator avoidance, feeding, reproduction, maternal behavior and social interactions. Although specific odors can trigger innate responses, most odor stimuli acquire behavioral significance upon learning and experience. The goal of our team is to identify the network mechanisms underlying the formation of olfactory memory traces across distributed brain regions. More generally,…

Optopath

OptoPath is an innovative platform entirely dedicated to research in experimental psychopathology in rodents and humans.

Organ_izing the cells

3D cell culture i.e. the art of organ-izing cells by cultivating them in configurations that more closely mimic the in-vivo environment is widely considered as the main route towards more physiologically relevant in vitro models. Yet providing simple, large scale and standardized solutions remains a key challenge for the widespread adoption of such cell-based models in laboratories and later in the pharmaceutical industry. Pioneers in the field of 3D brain cultures undoubtedly demonstrated the huge potential of such models in neuroscience. They also point out that novel tools and materials are required to advance their maturation (complexity) and scalability. This…

PARCA (Platform for Addiction Research and Clinical Assessment)

EXPERTISE• Clinical research on addiction (substances and/or behaviors) and comorbidities• Multidimensional and standardized assessment of the severity of addiction in humans• Ecological Momentary Assessment and Ecological Momentary Intervention• Data analysis, article writing and publication in scientific journal SERVICES• Design, set up and conduct clinical studies in patients treated for addiction (e.g. cohort ADDICTAQUI) or recruited in general population• Assessment of patients treated in addiction health services (e.g. CH Charles Perrens ; Bizia)• Recruitment of patients for clinical studies on addiction (SANPSY partnerships)• Training in addiction and psychiatric comorbidities assessment tools (ASI-Addiction Severity Index; MINI- Mini International Neuropsychiatric Interview)• Communication, training…

Pathophysiology of declarative memory

Our team aims at characterizing the neurobiological basis of addiction and molecular basis of traumatic memories. By applying a translational research, our work is dedicated to offer and develop new treatment Our aim is to identify psychobiological bases of declarative memory (DM) alterations occurring in aging and post-traumatic stress disorder (PTSD). We have developed specific behavioral models of age- and PTSD-related memory alterations in the mouse. Using these models, we search correlates of the cognitive changes at the system, cellular and molecular levels of brain activities. To establish causality links between neurobiological and cognitive changes, we then combine interventional approaches…

Pathophysiology of neuron-oligodendrocyte interactions

Bidirectional neuron-glia interactions provide the framework for the organization of the brain. One type of glia cell, the oligodendrocyte is well known for the establishment of myelin sheaths around axons, the neuronal output structure. Myelin enables fast communication between neurons, but oligodendrocytes fulfill additional physiological functions which we only start to understand. Our research aims to address this knowledge gap by understanding the physiology of oligodendrocytes and their impact on neuronal communication and vice-versa. We address our research questions on the single cell and micro-circuit level. Alterations of oligodendrocytes are a common feature among several neurodegenerative diseases. By combining our…

Pathophysiology of proteinopathies

Our translational research is dedicated to uncovering the pathophysiology of Parkinson’s disease and works towards development of therapeutic solutions. Our team is best known for its work on L-DOPA-induced dyskinesia (LID), serious motor complications associated to the chronic dopamine replacement therapy. Recently, we work on a collaborative project using innovative nanotechnology as a new means of imaging living systems and of delivering therapy. Innovative techniques: Optical nanoprobes, lysososomal targeted nanoparticles, kinematics, gene transfer, preclinical studies

PET platform

La plateforme de recherche en Tomographie par Emission de Positons (TEP), rattachée au laboratoire INCIA (UMR CNRS 5287), est dédiée à l’imagerie moléculaire à l’aide de médicaments radiopharmaceutiques (MRP) marqués par des émetteurs de positons (fluor-18 et gallium-68). Son expertise est triple : Synthétiser des MRP utilisés en recherche clinique et mener une activité de recherche et développement sur de nouveaux MRP (imagerie et thérapie). Mener des essais cliniques, promus par des structures académiques (CHU, université) ou des partenaires industriels, dans les domaines de l’oncologie et de la neurologie, avec des MRP commerciaux ou sans autorisation de mise sur le marché…

Phenovirt

The Phenovirt platform is dedicated to phenotype and treat healthy humans and patients using E health technologies

Phycell

The goal of PhyCell is to provide the scientific expertise and device to tackle questions requiring electrophysiological techniques and/or calcium imaging. Phycell provides three fully equipped rigs for extra- and intracellular recordings and calcium imaging.

Physiology and preclinical pharmacology of neuropsychiatric disorders (P3TN)

Our team aims at dissecting at the molecular, cellular, synaptic, and network levels, the neural bases of cognitive functions and behaviors in normal and pathological conditions. Special emphasis is placed on multilevel analysis of social behaviors combining genetic, molecular, cellular, and biochemical approaches, as well as in vivo electrophysiological recordings in freely behaving or head-restrained mice. Innovative techniques: in vivo electrophysiology in freely behaving transgenic mice, cognitive and social behavioral analysis.

Physiopathology and therapeutic approaches of stress-related diseases

Our team aims at characterizing the neurobiological basis of addiction and molecular basis of traumatic memories. By applying a translational research, our work is dedicated to offer and develop new treatment for addiction. We successfully revealed neurobiological substrates involved in the transition to cocaine addiction. We recently demonstrated that pregnenolone can protect the brain from cannabis intoxication, that serves as a ground for clinical research. Innovative techniques: neurosteroids biochemistry, In vivo HPLC-microdialysis, model of addiction, rodent behavioral testing.

Planar polarity and plasticity

Our group is interested in elucidating the role of the mammalian planar cell polarity (PCP) in the developing and adult nervous system. We study how defects in PCP genes cause sociability impairements and memory imbalances, typical of Autism spectrum disorder. To this goal, we explore the impact of PCP proteins (i.e. Vangl2 and Scrib1) on synaptic functions and characterise the PCP protein complexes and protein interactions. In parallel, we use the inner ear as a model to address the role and mechanisms of PCP signalling and identify novel molecular actors of PCP pathway. Innovative techniques: primary cultures of brain slices…

PRNPP Facility

The PRNPP is dedicated to conduct sleep, neurological and mental disorders trials, as well as pharmacological trials on health subjects and patients

Psychobiology of vulnerability to drug addiction

Our team works at the understanding of the psychobiological mechanisms of addiction, notably to cocaine and tobacco. Drug use can lead to behavioral disorders of which an extreme version is addiction. This psychopathology is not a mere excessive drug use, but is defined as a loss of control over use, which is particularly reflected in the maintenance of use despite its adverse effects. Critically, all users are not equally at risk for addiction, however. Our experimental strategy consists in integrating these characteristics of the pathology, i.e. loss of control over drug use and individual vulnerability, for an increased face and…

Purinergic mediated neuroinflammation and brain disorders

Neurological disorders rely on alterations of the central or peripheral nervous system that are caused by impairments of neuronal transmission or more global perturbations of local circuits that implicate glial cells. The scientific goal of our team is to understand the contribution of neuronal versus inflammatory signaling in brain disorders including amyotrophic lateral sclerosis (ALS), attention deficit/hyperactivity disorders (ADHD), chronic pain, and anxiety-related disorders. Our objectives are to determine (i) the contribution of purinergic signaling as a dual system, and (ii) the modulatory function of peptidergic signaling, both capable to regulate neuronal synaptic activation and microglial neuro-inflammatory reaction as well…

Quantitative imaging of the cell

Our team aims at developing novel imaging techniques to decipher protein organization and dynamics at high spatial and temporal resolutions. More precisely, four main research areas are dedicating to develop: 1) Novel instruments for super-resolution microscopy of living samples, 2) Analytical tools for object segmentation, tracking and visualization, 3) High Content Screening Microscopy to quantify the dynamics of active proteins within the living cells, using super-resolution microscopy and 4) Bioengineering for micropatterning and microfluidics to control cell geometry and their local chemical environment. Innovative techniques | Tools for single molecule localization, tracking and quantification, 3D imaging of thick biological specimens,…

Sleep, addiction and neuropsychiatry

We study substance and non-substance addiction and have developed a human model of addiction. Our studies tend to better characterize the common phenomenology accross addictions and its determinants, using a multidisciplinary approach (clinical neurobiology, epidemiology, psychology and sociology), with a special interest on craving and its behavioral correlates. The main research tool is an open prospective cohort (ADDICTAQUI) started in 1994, of over 3500 patients requesting treatment for addiction. Innovative techniques: Patient prospective cohort, Addiction Severity Index, Ecological Momentary Assesment

Sleep/Wake, Aging, Neuroimaging (SWAN)

A core objective of our research is to examine the impact of sleep/wake disturbances on daytime functioning to elucidate the etiology and pathophysiology of age-related CNS disorders. Cognitive symptoms and physiological malfunctioning are assessed in clinical studies but also in population-based cohorts. We apply advanced neuroimaging techniques using multimodal approach coupling morphological and functional MRI techniques and dailylife assessment based on connected devices for sleep/wake cycle (actigraphic watch) and cognition (EMA on smart phone). More specifically, daily life evaluations unravel the intra-individual variability of physiological and cognitive functioning; we attempt to understand its anatomical and functional bases by analysing it…

Spatio-temporal and mechanical control of motile structures

Our goal is to decipher at the molecular level the spatiotemporal and mechanical mechanisms which control the architecture and dynamics of motile structures. First in the context of cell migration by studying integrin-based adhesion sites and the actin-based lamellipodium. Second in the context of neuronal structural plasticity by studying the actin cytoskeleton in axons and dendritic spines. Exploration of these new dimensions requires an innovative and multidisciplinary approach combining cell biology, biophysics, biomechanics and advanced optical microscopy techniques including super-resolution microscopy, single protein tracking and quantitative image analysis. Innovative techniques: single molecule localization microscopy (PALM, STORM, uPAINT), super-resolution microscopy (RESOLFT),…

Structural Biology and Engineering of Neuronal Proteins

The interests of our team lay at the interface of structural biology, protein engineering, and cellular neuroscience. We aim to understand molecular principles of neuronal signalling in health and disease, and to translate these to the cellular and organismal level. We use mammalian protein expression, protein chemistry, biophysical methods, X-ray crystallography and cryo-electron microscopy to study the interaction determinants and structures of synaptic protein complexes involved in neurodevelopmental disorders and neuronal disease. We use combinatorial methods and protein engineering to discover novel binders and manipulate protein sequence, structure and function, both to facilitate structural studies as well as enable therapeutic…

Synapse in cognition

Our main objective is to understand the link between synapse and cognition at the synaptic and circuit level. Our recent results show that several mental retardation (MR) mouse models exhibit functional synaptic deficits at cortical projections to the lateral amygdala (LA), a structure involved in the coding of fear memory. We will examine the role of MR proteins in the process of memory formation by analysing biochemical, morphological and physiological changes of cortico-LA synapses in mice submitted to fear conditioning. Innovative techniques: In vivo electrophysiology, in vivo two-photon imaging of neuronal activity, fluorescence-activated sorting of synaptosomes

Synapses and neural circuits in behaviour

The research carried out in our group ambitions to link cell biological mechanisms of proteins and lipids involved in glutamatergic synaptic function and dysfunction. Much of our work has focused on the roles of kainate receptors, a subject in which the group is internationally recognised. We elucidated new biophysical and pharmacological properties of kainate receptors in the developing hippocampal circuits and in temporal lobe epilepsy. Our group has also broken new ground with highly original work on the role of prostaglandins and other lipids in synaptic plasticity. Great efforts are made to develop new methods for investigating the connectivity and…

Synaptic plasticity and super-resolution microscopy

Our group objective is to better understand higher brain function and disorders through innovative and advanced technological developments. To this end, we are applying novel superresolution microscopy approaches (STED microscopy), giving us a much more complete and refined view of the dynamic behavior and plasticity of neuronal synapses and their interactions with glia cells inside living brain slices. This approach is complemented by a combination of 2-photon imaging and patch-clamp electrophysiology to address the underlying synaptic mechanisms of plasticity in the mammalian brain. Innovative techniques: STED microscopy in brain slices and in vivo, two-photon microscopy, glutamate uncaging, calcium imaging, biophysical…

SynTeam

The pathological aggregation of neuronal proteins is a key and often causal event in many neurodegenerative diseases. Synucleinopathy, characterized by the accumulation and spread of aggregated amyloid forms of alpha-synuclein in the brain, is observed in Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies. Understanding the molecular mechanisms involved in the amyloid self-assembly of this small synaptic protein, tracking the cellular processes by which neurons handle its pathogenic conformational changes and deciphering the inter-neuronal propagation pathways of these aggregated forms are crucial aspects in neurodegenerative research and hold significant interest for therapeutic development. It is now…

Transcriptomic

Transcriptomics Platform performs gene expression studies as part of scientific projects in various tissues in mice, rats, humans… Our high throughput equipment in quantitative PCR (qPCR) allows us to handle 20 plates 96 wells or 384 wells a day. More than 4000 couples of oligonucleotides are listed in our database. Transcriptomics Platform is organized in 3 rooms : a 25m2 laboratory room for samples preparation, a room for the primers preparation and a room for the qPCR. Transcriptomics Platform is at the service of all Neurocentre Magendie members but also accessible) to all the scientific community (public and private users).

Translational research in neurogenetic diseases (NRGEN)

The team gathers together researchers interested in a continuum of overlapping neurogenetic disorders covering spinocerebellar degenerations (ataxias, spastic paraplegias), motor neuron diseases (amyotrophic lateral sclerosis, hereditary spastic paraplegias, neuropathies) and neurodegeneration with brain iron accumulations (NBIA). Our goal is to dissect the molecular bases of these neurogenetic diseases with the long-term goal of developing specific therapies, which are lacking for almost all of them. To this end, we use a combination of genetic analyses (exome, genome, repeat expansion detection), phenotype-genotype correlations, biomarker searches and functional analyses (cellular, yeast and mouse models).