INMED - INSERM U901

Mediterranean Neurobiology Institute

Director : Alfonso REPRESA

Campus Luminy - BP 13
163, route de Luminy
13273 Marseille CEDEX 9
France

INMED is a joint research institute of INSERM and Aix-Marseille University. The main objectives of its scientific teams are the study of the development and plasticity of the brain and the pathologies of brain development that can disrupt, among other things, the acquisition of language, cognition and motor skills, or can lead to a more or less severe epileptic condition.

INMED is composed of international researchers and professors brought together in 12 established research teams qualified by our institutions and 4 emerging research teams.

INMED has common facilities and services organized in platforms: a functional imaging platform (two-photon microscopes, confocal, open fields, image analysis systems …), a post-genomics platform (to create rat / mouse models for neurological diseases), a molecular and cellular biology platform (primary and organotypic cultures, virus manipulation, human cell culture, bacteriology rooms, DNA electrophoresis, PCR and quantitative PCR …), animal houses, about 30 electrophysiology stations (in vivo and in vitro), and dishwashing, IT, and histology services.

Pictures from the INMED laboratory

Research teams

Twelve out of the sixteen INMED teams are affiliated to the neuroscience master’s program and can thus train neuroscience master’s students and offer them projects to apply for a Neuroscience Ph.D. scholarship.:

  • Pathophysiology of synaptic plasticity
  • Neuronal dynamics and functions of the basal ganglia
  • Maturation and plasticity of cortical maps
  • Maturation of cortical GABAergic microcircuits Pathophysiological
  • Mechanisms of Early Epilepsy
  • Pathophysiology of Temporal Lobe Epilepsy
  • Early activity in the developing brain
  • Epilepsies and childhood diseases
  • Physiological and pathological oscillations in the basal ganglia
  • Post-traumatic plasticity, neuronal survival and rewiring
  • Extracellular matrix and pathophysiological maturation of prefrontal networks
  • Neuronal coding of space and memory

Pathophysiological Mechanisms of Early Epilepsy (Laurent Aniksztejn)

Early epileptic encephalopathies are very rare diseases beginning in the first 3 months of life and characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. Ohtahara syndrome is the earliest and one of the worst forms of early epileptic encephalopathies, characterized by an electro-encephalogram (EEG) pattern named “suppression burst”, described as generalized and multifocal, high-voltage, spikes and sharp wave complexes alternating with periods of suppression of electrical activity. Their etiology remains elusive and their outcome is often very poor with no efficient treatments to date. Numerous genes have been associated with this condition including a major one: the KCNQ2 gene, which encodes one of the main subunits of Kv7 channels underlying M current (IM) in many neurons. This current plays a crucial role in controlling neuronal excitability. Furthermore, alteration of proteins involved in glutamate recycling in glial cells strongly compromises proper electrophysiological development of the brain and has been associated to early epileptic encephalopathies. These proteins are: i) glutamine synthetase (GS), a cytosolic enzyme expressed only in glial cells, and ii) glutamate carrier 1 (GC1), the main mitochondrial glutamate transporter in astrocytes. Our project aims to better understand the pathophysiological basis of early epileptic encephalopathies; our general idea is that alteration of one of these 3 proteins could result in neuronal network hyper-excitability.

Members

Laurent Aniksztejn, Hélène Becq (Clot-Faybesse), Florence Molinari.

Research axes

  • Role of KCNQ2 and M currents in early epileptic encephalopathies
  • Role of astrocytic glutamine synthetase and mitochondrial glutamate carrier 1 in these epilepsies in this disorder
  • Techniques:
  • Molecular biology
  • Biochemistry
  • Cell culture
  • Calcium imaging
  • Electrophysiology (on slices or cells)

Keywords

Potassium channels, glutamate, glutamine synthetase, glutamate transporter, astrocytes, hyper-excitability, epilepsy.

Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Maturation and plasticity of cortical maps (Ingrid Bureau)

The team investigates the structure / function relationships of neuronal networks in sensory cortex. A distinct feature of sensory cortex is the precise organization of connectivity in columns and laminae. What function does it serve? Under what circumstances is this organization altered and with what consequences for sensory integration? We are most particularly interested in the function of cortical circuits in associative learning where animals learn to anticipate a reward when a particular sensory stimulus occurs. This training enlarges the neuronal representation of the conditioned stimulus in the cortical map as if areal size encoded the emotional significance of stimuli in cortex. Our goal is to identify the circuits underlying this transformation and to study how their plasticity contributes to the control of behavior. To this aim, we combine behavioral studies and electrophysiology in vitro and in vivo. Our model system is the barrel cortex, a region of the primary somatosensory cortex dedicated to whiskers.

Members

Ingrid Bureau, Jeremy Camon, Melissa Erlandson, Romane Cecchi. Total : 1 HDR (in progress).

Research axes

  • Associative plasticity of cortical circuits mapped in vivo and in brain slices
  • Cortical defects and learning disabilities

Techniques

  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Animal behavior

Keywords

Learning, behavior, sensory cortex, barrel cortex, cortical map, circuits, connectivity, synapse, plasticity.

Animal cognition and behavior - Excitability, synaptic transmission, network functions - Sensory systems

Epilepsies and childhood diseases (Nail Burnashev)

Our team is interested in investigating how brain networks develop and how early seizures lead to long lasting neurological sequels in order to improve treatments. How are seizures generated? What are their consequences on brain maturation?
We decided to study 3 types of early epilepsies:

  • idiopathic seizures and anti-epileptic drugs action
  • epilepsies associated with brain malformation: tuberous sclerosis complex
  • neonatal epileptic encephalopathy with suppression burst and glutamate homeostasis

We will focus on the dynamic regulation of chloride that underlies the excitatory action of GABA in wild-type and in epileptic models (KCC2 and NKCC1 knock-out, TSC1 and 2 mutant mice). We will also investigate the presence of hub neuronal generators which could lead to the generation of seizures. In parallel, we want to study the importance of glutamate transporters on neonatal epilepsies with suppression bursts.

Members

Nail Burnashev, Ilgam Khalilov, Alexandre Pons-Bennaceur.

Research axes

  • The dynamic regulation of chloride in cortical networks : maturation and alterations during delivery
  • The dynamic regulation of chloride in autism, epilepsies and other developmental disorders
  • Identification of neuronal generators of seizures
  • Neonatal epileptic encephalopathy with Suppression Burst and glutamate homeostasis

Techniques

  • Molecular biology
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)

Keywords

GABA, chloride, epilepsy, neurodevelopmental disorders, autism, tuberous sclerosis, seizures, glutamate transporters, astrocytes.

Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Extracellular matrix and pathophysiological maturation of prefrontal networks (Pascale Chavis)

Reelin and perineuronal nets are major components of the extracellular matrix. Reelin plays a fundamental role in neuronal development and synaptic physiology in the postnatal central nervous system (CNS). Perineuronal nets are involved in the closure of critical periods in the visual cortex and are thought to be responsible for the stabilization of mature synapses. Reelin and perineuronal nets are major candidates in the etiology of schizophrenia, and reelin is a vulnerability factor for bipolar disorder, depression and autism. Dysfunctions of the prefrontal cortex prefrontal cortex are one of the characteristic features of these psychiatric illnesses. The prefrontal cortex is involved in various cognitive and executive functions (careful planning, inhibition, working memory), and has the remarkable property of being the last structure of the brain to mature. In this context, our project is based on the elucidation of the molecular and cellular mechanisms that govern the sensitive periods of postnatal maturation of the prefrontal cortex.

Members 

Pascale Chavis, Marion Benoist, Lamine Bouamrane, Séverine Stamboulian-Platel, Olivier Lassalle. Total : 1 HDR.

Research axes

  • to elucidate how reelin and perineuronal nets shape structural, functional and behavioral development in the maturing prefrontal cortex
  • to identify morpho-functional deficits of the maturing prefrontal cortex and abnormal behavior in murine models of psychiatric diseases involving reelin and perineuronal nets.
  • to define and test therapeutic strategies to correct aberrant prefrontal cortex maturation

Techniques

  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Pharmacology
  • Animal behavior
  • Optogenetics

Keywords

Extracellular matrix development, prefrontal cortex, behavior, cognition, executive functions, synapse plasticity, schizophrenia, bipolar disorder, depression, autism, therapy.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Maturation of cortical GABAergic microcircuits (Rosa Cossart)

Most adult cortical dynamics are dominated by a minority of highly active neurons distributed within a silent neuronal mass. If cortical spikes are sparse, spiking of single distinct neurons, such as hub neurons (Bonifazi et al. 2009), can impact on network dynamics and drive an animal’s behavior. It is thus essential to understand whether this active and powerful minority is predetermined and if true to uncover the rules by which it is set during development. Current work in the lab aims at testing the possibility that birthdate is a critical determinant of neuronal network function into adulthood, in health and disease. More specifically, we reason that neurons that are born the earliest are primed to participate into adult network dynamics. This hypothesis is considerably fed by our past work aiming at understanding how cortical networks function and assemble during development. To test this hypothesis, and more generally to describe structure-function relationships in cortical networks, we have developed a multidisciplinary approach that combines in vitro and in vivo calcium imaging and electrophysiology, neuroanatomy, notably from clarified intact structures, mathematical analysis and mouse genetics.

Members

Rosa Cossart, Agnès Baude, Yannick Bollmann, Loris Cagnacci, Dorian Champelovier, Claire Gouny, Caroline Haimerl, Arnaud Malvache, Laura Modol-Vidal, Catherine Pauchet, Susanne Reichinnek, Laurène Save, Alessandro Torcini, Thomas Tressard, Pierre Trubert. Total : 2 HDRs.

Research axes

  • Understand the role of early born neurons in cortical network activity during development and into adulthood, in health and disease.
  • Dissect the connectome and the functional topography of early-born cortical neurons.

Techniques

  • Molecular biology
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Optogenetics
  • Electroencephalography (EEG)
  • Bioinformatics

Keywords

Early-born neurons, development, epilepsy, cortex, network, modeling, electrophysiology, genetic fate-mapping.

Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Normal and Epileptic Circuits at Work (Valérie Crépel)

We investigate neuronal computation and plasticity in normal and pathological conditions. Our studies are conducted at multiscale levels i.e. from the individual spine to the microcircuit.

We focus our interest on:

(i) Kainate receptors in the physiopathology of temporal lobe epilepsy. Temporal Lobe Epilepsy (TLE) is the most common form of partial epilepsy in adults is often refractory to pharmacological medication. Moreover, patients with TLE also often suffer from comorbid disorders including cognitive impairments. Therefore, it is crucial to better understand the physiopathology of TLE in order to propose new anti-epileptic strategies and shed light on putative alterations of neuronal computation.

(ii) Mechanisms of information storage in the cerebellar cortex. The cerebellar granule cell to Purkinje cell synapses are some of the most numerous central excitatory synapses. In vitro studies have demonstrated that their strength can be modified by various plasticity mechanisms, which may mediate information storage or homeostatic regulation. Our research aims to relate specific types of synaptic plasticity mechanism to specific functions.

Members

Valérie Crépel, Païkan Marcaggi, Angélique Péret. Total : 1 HDR.

Research axes

  • Kainate receptors in the physiopathology of temporal lobe epilepsy
  • Mechanisms of information storage in the cerebellar cortex

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Optogenetics
  • Electroencephalography (EEG)

Keywords

hippocampus, cerebellum, learning, spatial navigation, plasticity, circuit, synapse, kainate receptors, receptors coupled to G proteins, calcium, epilepsy, head trauma, therapy.

Animal cognition and behavior - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Neuronal coding of space and memory (Jérôme Epsztein)

The hippocampus is involved in the formation of memories for the events we experience every day (episodic memory) and in our capacity to locate ourselves and navigate in familiar environments without the need of a map (spatial navigation). For a long time, these two functions of the hippocampus were separated. However, recent work suggests that there is a link between these two functions in the mammalian brain. Our aim is to understand the mechanisms of spatial navigation both at the cellular and network level. This could help us understand episodic memory formation. To address this question, we perform extracellular recordings of hippocampal cells activity. Extracellular recordings can only record the spiking output of neurons but not the intracellular mechanisms leading to that spiking. This is why we recently contributed to the development of a new technique allowing reliable intracellular recordings of hippocampal neurons in freely behaving animals. Intracellular recordings allow us to study the mechanisms of spatial coding in great detail. Indeed, we do not only record the output of cells in form of action potentials but also their inputs in form of synaptic potential and intrinsic properties. We can also characterize the morphology of the recorded cell and stimulate or silence a given cell through direct current injection. Because intracellular recordings are difficult to perform in freely behaving animals, we also perform such recordings in head- fixed animals navigating virtual reality environments.

Members

Jérôme Epsztein, Julie Koenig, Geoffrey Marti, Peter Morgan, François-Xavier Michon,  Romain Bourboulou.

Research axes

  • An intracellular approach to spatial coding in the hippocampus in real and virtual environments

Techniques

  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Animal behavior

Keywords

Network, hippocampus, behavior, virtual environment, spatial navigation, memory, episodic memory.

Animal cognition and behavior - Excitability, synaptic transmission, network functions

Physiological and pathological oscillations in the basal ganglia (Constance Hammond)

1- Early signatures of Parkinson’s disease ?

We have discovered an early signature of Parkinson disease in two rodent genetic models (Dehorter et al 2009, 2012, 2014). We hypothesized that such early signatures would be also present in midbrain dopaminergic neurons. We first characterized the control development of these neurons (Ferrari 2012, Pearlstein 2015). We are now characterizing their pathological development.

2- Hub neurons in the subthalamic nucleus ?

Subthalamic neurons generate pathological oscillations in animal models of parkinsonism and in patients suffering from Parkinson disease. The underlying mechanisms are not yet fully elucidated. We test the hypothesis that a subpopulation of early born subthalamic neurons has intra-nucleus collaterals that allow mobilizing a large fraction of other subthalamic neurons in response to strong afferent excitation. When deprived of dopamine, these “hub neurons” would be more excitable and entrain many subthalamic neurons to continuously oscillate.

Members 

Constance Hammond, Laurie-Anne Gouty-Colomer, Edouard Pearlstein. Total : 1 HDR.

Research axes

  • Translational research

Techniques

  • Molecular biology
  • Immunostaining, histology or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy

Keywords

Basal ganglia, Parkinson, development , patch clamp, biphotonic calcium imaging

Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Motor systems

Early activity in the developing brain (Rustem Khazipov)

Our team is interested in the neuronal network activity expressed in the brain at the early developmental stages. In particular, we study the generation of the patterns of activity in the sensory (somatosensory and visual) cortices, with the aim to understand the neuronal network mechanisms of the earliest patterns, early gamma oscillations and spindle-burst, and their roles in the activity-dependent formation of the cortical maps. Consequently, we extrapolate our hypothesis made in the animal models to the human premature neonates, with the aim to understand how the brain operates during fetal stages. We are also studying the developmental changes in GABAergic neurotransmission, and its roles in the generation of physiological and pathological activities in the developing brain (hypoxia, epilepsy and pain).

Members 

Rustem Khazipov, Marat Minlebaev, Ana Rita Lourenco Inacio. Total : 1 HDR.

Research axes

  • Physiological patterns of activity in the developing brain
  • Developmental changes in GABA signaling
  • Epileptic activity in the developing brain
  • Neuroprotection of newborn during delivery

Techniques

  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Movement or posture analysis, electromyography (EMG)
  • Brain imaging – Animal
  • Optogenetics
  • Electroencephalography (EEG)

Keywords

Development, neonate, electroencephalogram, cortex, barrel system, visual system, GABA, epilepsy, hypoxia, pain, oxytocin, fetal alcohol syndrome.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Sensory systems

Pathophysiology of synaptic plasticity (Olivier Manzoni)

Regulation of mood and emotion is critical for mental health. Major neuropsychiatric disorders including mental retardation, autism, schizophrenia, depression and addiction are accompanied by significant social, emotional and cognitive problems. Surprisingly, the neuronal substrates of emotional perturbation are seldom studied in the context of these pathologies. In neuropsychiatric diseases, disruption of a molecular cog of the synaptic machine causes or result in deficits in synaptic plasticity (SP) and leads to abnormal information processing.

Our specific goal is to unravel synaptic dysfunctions and propose new therapeutic venues for synaptopathies. Our integrated approach is composed of three lines of research:

1. Audit of physiological synaptic networks

We will identify and study the role of sensitive periods of synaptic plasticity, determine the molecular components allowing the full range of synaptic plasticity and establish morphological and behavioral correlates of normal synaptic activity.

2. Identification of synaptopathies in neuropsychiatric diseases

We postulate that in neuropsychiatric diseases the reduction of the range of synaptic plasticity participates to the reduction of cognitive and behavioral flexibility.

Pathologies resulting from aberrant synaptic plasticity are due to a disruption or insufficiency in the expression of specific gene products and/or to environmental insults.

To address these two dimensions of pathological synaptic plasticity and based on strong preliminary results we will search for alterations of synaptic plasticity in mouse models of schizophrenia, autism, mental retardation, addiction and dietary deficiency.

3. Rescue

Based on the knowledge gained in the previous aims, we will use already available and newly developed pharmacological agents and nutritional strategies acting on neurotransmitter systems and/or transduction pathways to restore normal synaptic plasticity and behaviors in diseased mice.

Members

Olivier Manzoni, Anissa Bara, Axel Bernabeu, Olivier Lasalle, Antonia Manduca, Henry Martin, Marion Deroche, Andrew Scheyer, Anne-Laure Pelissier. Total : 2 HDRs.

Equipe Manzoni, INMED

Research axes

  • Auditing physiological synaptic networks
  • Identifying and rescuing synaptopathies in neuropsychiatric diseases

Techniques

  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal behavior
  • Optogenetics

Keywords

Synapse, synaptic plasticity, accumbens, prefrontal cortex, endocannabinoid, mGluR, pharmacotherapy, addiction, autism, Fragile X, nutrition, adolescence, omega 3

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Post-traumatic plasticity, neuronal survival and rewiring (Claudio Rivera-Baeza)

Our team is interested in brain rewiring and plasticity after injury. Brain trauma, also called traumatic brain injury (TBI), is the leading injury-related cause of death and permanent disability. Every year, in France, TBI touches 130 000 persons and over 10 million in the world. 20% of patients suffering from brain insults die within one month, 75 % of TBI survivors suffer from the accident their whole life and up to 25% never return to professional life.

In this context, we focus on the early stages following TBI to understand how a physiologic network transforms into a pathologic one. We are using two models: a pilocarpine-induced model of temporal lobe epilepsy and a model of controlled-cortical impact in rodent.

Our research plan is:

  • To establish a solid link from molecular mechanisms controlling changes in cation-chloride cotransporter (CCC) expression, trafficking and kinetic regulation to the systems-level phenomena following traumatic brain conditions leading to cell death and epilepsy.
  • To establish novel strategies for decreasing the significant fraction of patients with brain injuries, who do not recover to be functional member of our society.

Members

Claudio Rivera-Baeza, Christophe Pellegrino, Geneviève Chazal, Emmanuelle Goubert, Nazim Kourdougli. Total : 1 HDR.

Equipe Rivera, INMED

Research axes

  • Developmental plasticity
  • Post traumatic plasticity
  • Depression
  • Chloride homeostasis

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Electroencephalography (EEG)

Keywords

Neuronal death, plasticity, injury, traumatic brain injury, epilepsy, cation-chloride cotransporters, membrane targetting, network activity and GABAergic signalling.

Animal cognition and behavior - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Neuronal dynamics and functions of the basal ganglia (David Robbe)

Every day, we perform sequences of movements with a high level of precision in terms of trajectories and timing. This is the case in seemingly trivial behaviors such as bringing a fork loaded with food to our mouth, and in more complex situations like driving a car, performing sports and arts. All these motor skills require prolonged training (think of how long it takes a child to learn to use a fork!) and after extensive practice, they can be performed in a highly automatic (or habitual) manner. The neuronal mechanisms that contribute to the learning of motor skills and to their execution are still largely unknown. Several brain regions are involved and among them the role of the basal ganglia (a subcortical network whose dysfunction can lead to Parkinson’s and Huntington’s diseases) is highly debated.

The goal of the lab is to uncover the function and the type of neuronal computation of the basal ganglia during the learning and execution of motor skills. To reveal both the function and computation of the basal ganglia our experimental approach combines :

  1. the development of original behavioral paradigms that capture the main features of motor skills,
  2. recordings of spiking activity in the striatum and connected areas such as the motor and sensory cortices in behaving rodents,
  3. in vivo pharmacological and optogenetic perturbations,
  4. statistical analysis of behavioral and neuronal data, and of their interaction.

Members

David Robbe, Maria Teresa Jurado-Parras, Loubna Khalki, Laëtitia Lalla,Wahiba Taouali, Ludovic Petit, Carola Sales-Carbonell. Total : 1 HDR (expected July 1st, 2016).

Equipe Robbe

Research axis

Neuronal bases of motor learning and control.

Techniques

  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Movement or posture analysis, electromyography (EMG)
  • Optogenetics
  • Electroencephalography (EEG)
  • Bioinformatics

Keywords

Motor skills, learning, basal ganglia, cortex, neuronal coding, behavior, electrophysiology, optogenetics, multi-electrode.

Animal cognition and behavior - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Motor systems

Cortical development disorders and neuronal migration (Carlos Cardoso, Alfonso Represa)

Our team investigates cortical development disorders, which are important causes of mental retardation and account for more than 40% of drug-resistant childhood epilepsy.
We conduct integrated multidisciplinary studies involving morphologists, molecular biologists and electrophysiologists. In addition, we have established collaborations with clinicians and geneticists (European EPICURE project) providing us with a transversal appreciation of our researches.
We concentrate our efforts on:

1- the identification of new genes and molecular actors involved in normal developmental processes and altered on cortical development disorders for a better understanding of the link between genotype and phenotype;

2- the characterization of the physiopathological mechanisms responsible for epileptogenesis in malformations of cortical development, in order to precisely identify the seizure-generating zone, to describe its properties and the mechanisms of seizure generation, and to ultimately suggest new therapeutic approaches;

3- understanding the functional mechanisms responsible for cognitive impairments in pediatric epilepsies.

Members

Carlos Cardoso, Alfonso Represa, Françoise Watrin,  Pierre-Pascal Lenck-Santini, Antoinette Bernabe-Gélot, Véronique Brevaut-Malaty, Agathe Deparis, Antonio Falace, Lauriane Fournier, Jean-Bernard Manent, Fanny Martineau, Surajit Sahu. Total : 2 HDRs.

Research axes

  • Pathophysiology of cortical development disorders
  • Morpho-functional analysis of cortical networks in animal models of neurodevelopmental disorders
  • Functional mechanisms responsible for cognitive impairments in pediatric epilepsies.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Electroencephalography (EEG)

Keywords

Development, epilepsy, cortex, cognitive disorders, neuronal migration, animal models

This team is not affiliated to the Neuroscience Master’s.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions

Developmental Plasticity of GABAergic synapses (Jean-Luc Gaiarsa, Igor Medyna)

The goal of our project is to elucidate how neurotrophic factors and chloride homeostasis contribute to developmental forms of GABAergic synaptic plasticity during physiological conditions and in animal models of neurological disorders. γ-amino butyric acid (GABA) is a key regulator of brain function and plays a central role in its development. GABAergic interneurons regulate neuronal excitability, synaptic integration and network oscillation dynamics and as such are crucial for many cognitive functions. As a result, defective GABA levels and GABAergic transmission are strongly associated with cognitive dysfunction and neurological disorders. Understanding the factors that modulate the development and efficacy of the GABAergic system is thus of particular interest because it may provide key insights into disease states and potential treatments. The project combines molecular and cellular biology, electrophysiology, biochemistry and imaging on primary cultures of hippocampal neurons and acute brain slices.

Members

Jean-Luc Gaiarsa, Igor Medyna, Diabé Diabira, Camille Dumon, Nadine Ferrand, Lucie Pisella, Christophe Porcher, Baptiste Riffault. Total : 3 HDRs.

Research axes

  • Trophic role of leptin on GABAergic synaptogenesis and plasticity
  • Dynamic regulation of GABAA-receptors at synaptic sites
  • Regulation of chloride homeostasis

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)

Keywords

Neurotrophines, leptine, synaptogenesis, GABA, development, epilepsy, chloride, cation-chloride cotransporters, synapse.

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system - Excitability, synaptic transmission, network functions

Genetic and epigenetic effects on neurodevelopment: investigation of Prader-Willi (Françoise Muscatelli-Bossy)

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disease characterized by a range of feeding, cognitive and social behavioral disturbances and respiratory deficiency. The cause of this disease is genetic and the candidate genes are all regulated by genomic imprinting, an epigenetic mechanism leading to a paternal expression of those genes, the maternal alleles being normally silenced. Our team has identified and characterized the human MAGEL2 and NECDIN genes as candidates for PWS. Furthermore, MAGEL2 is mutated in patients with autism. Our goal is to understand, using genetically modified mouse models, the function of these two candidate genes and their physiopathological role of in PWS.

Our recent publications show that an alteration of the central oxytocinergic system just after birth results in a lack of suckling activity and, in adulthood, in deficits of social behavior and cognition. Both, early and late alterations, are rescued following an oxytocin administration just after birth. Our project is to study, through the postnatal development, the central role of oxytocin in the feeding, social and cognitive behavior in wild-type and mutant animals in order to facilitate the translation to clinical aspects.

Members 

Françoise Muscatelli-Bossy, Alessandra Bertoni, Laura Caccialupi, Marie-Solenne Félix, Valéry Matarazzo, Fabienne Schaller. Total : 2 HDRs.

Research axes

  • Role of oxytocin from birth, in normal and pathological conditions
  • Regulation and Physiological and cellular function of Magel2 and Necdin

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Animal behavior

Keywords

Epigenetics, genomic imprinting, development, autism, Prader-Willi syndrome, feeding behavior, oxytocin, serotonin, respiratory distress, therapy.

This team is not affiliated to the Neuroscience Master’s.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Sleep, autonomic and neuroendocrine systems

EPIPATH : EPIlepsies and comorbid PATHologies (Pierre Szepetowski)

The main focus of the EPIlepsies and comorbid PATHologies (EPIPATH) group is on the study and on the understanding of the relationships between epilepsies on the one hand, and numerous associated brain disorders on the other hand: autistic manifestations, cognitive impairment, speech and language impairments, paroxysmal dyskinesia, migraines, etc. Generally, the project should be viewed in the context of the relationships linking brain pathologies and brain development, and aims at deciphering the pathophysiology of epilepsies and of their comorbid conditions. The approach is multidisciplinary and includes clinical, genetic, molecular, biochemical, cellular, electrophysiological, and therapeutic levels.

Members 

Pierre Szepetowski, Sylvain Bauer, Nadine Bruneau, Robin Cloarec, Sandra Courtens, Manal Salmi. Total : 1 HDR.

Research axes

  • Pathophysiology of focal epilepsies and of epileptic encephalopathies of the epilepsy-aphasia spectrum: exploration of aGrin2a invalidation murine model.
  • Pathophysiology of congenital cytomegalovirus infections of the brain: analysis of a rat model of in utero infection of the brain.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Brain imaging – Animal

Keywords

Epilepsy, language, development, genetics, virus, therapeutic models

This team is not affiliated to the Neuroscience Master’s.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system
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