INT - UMR 7289

Timone Neuroscience Institute

Director : Guillaume MASSON

Campus Santé Timone
27, Bd Jean-Moulin
13385 Marseille CEDEX 05
France

An integrative approach of the normal and pathological functioning of the brain

Our objectives are to carry out world class research in fundamental neurosciences, from cellular to cognitive levels, and to fill the gap between fundamental and clinical approaches. Integrative neuroscience, by bridging levels of organization of the nervous system within a functional approach, plays an essential role in understanding the neural underpinnings of our behavior and of their dysfunctions in neurological and psychiatric diseases. By combining these approaches, the INT offers its researchers and clinicians opportunities :

  • to investigate and model normal and pathological brain and spinal cord function with an integrative approach, from neuron to behavior and from neurophysiology to multi-scale imaging. For a studied function (visual perception, corticospinal motor control, motivation, social cognition), the ultimate goal is to understand how neuronal activity is regulated at the cellular level then propagated by small cortical or sub-cortical networks and assembled within large systems  to control behaviors
  • to understand how the dysfunctions or the death of neurons and glial cells provoke neurological or psychiatric disorders such as motoneuronal diseases (ALS), spinal cord lesions (spasticity), executive control disorders (addictions, Parkinson’s disease), cognitive and social development pathologies (autism, bipolar disorders, schizophrenia), or pathologies associated with stress (post-traumatic stress, depression).

Pictures from the INT laboratory

Research teams

All INT 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 Ph.D. scholarship.

Inference in Visual Behaviours (InVibe) (Guillaume Masson)

The INVIBE team investigates the processing of different visual information and their integration to control eye movements in both humans and monkeys. Several levels of processing are tackled, from low-level mechanisms of visual motion processing up to contingent integrative stages taking into account decision-making and attention. Different levels of approaches are behavior, neurophysiology (electrophysiology, inactivation, fMRI) and theory (probabilistic models). INVIBE is therefore highly interdisciplinary. INVIBE has been labeled FRM team in 2018 and is supported by national (ANR, Foundations) and international (H2020) funding programs.

Members

MASSON Guillaume, GOFFART Laurent, MONTAGNINI Anna, PERRINET Laurent, IBOS Guilhem, SIMONCINI Claudio, BOUTIN Victor, DAMASSE Jean-Bernard, FRANCIOSINI Angelo, MANSOURPOUR Kiana, VENCATO Valentina.  Total: 3 HDRs.

Research axes

  • Oculomotor control in human and non-human primates
  • Visual perception and decision-making
  • Probabilistic coding in visuomotor transformations
  • Computational neurosciences : dynamical inference

Techniques

  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Psychophysical tests
  • Movement or posture analysis, electromyography (EMG)
  • Brain imaging and stimulation – Man

Keywords

Eye movements, Neurophysiology, Visual Psychophysics, Decision making, Attention, Bayesian Models.

Animal cognition and behavior - Computational neuroscience - Human cognition and behavior - Motor systems - Sensory systems

Basal Ganglia, Motivation and Reward (Christelle Baunez)

Our team uses a translational approach from rodents and monkeys to Parkinsonian patients to better understand the role of basal ganglia (BG) in motivation and reward-related processes, both in normal and dysregulated behaviors, such as addiction or impulse control disorders.

Members

BAUNEZ Christelle, APICELLA Paul, EUSEBIO Alexandre, GARCIA René, RAVEL Sabrina, WITJAS Tatiana, ALLEGRA Michele, DEGOULET Mickaël, BASANISI Rugerro, LGEUNSAT Asmae MARTEL Anne-Caroline, TIRAN CAPPELLO Alix. Total: 4 HDRs.

Research axes

  • Role of subthalamic nucleus in motivational and emotional processes
  • Role of DA and striatal neurons in goal-directed behavior and habits
  • Interaction between addiction and PTSD
  • Functional and directional cortico-subcortical connectivity in stroke

Techniques

  • Immunostaining, histology, flow cytometry
  • Microscopy (fluorescence, confocal, electronic…)
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo, on animals)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Brain imaging and stimulation – Man (fMRI, TMS…)
  • Optogenetics
  • Medical data analysis
  • Bioinformatics

Keywords

Basal ganglia, subthalamic nucleus, behavior, motivation, impulse, reward, addiction, cocaine, Parkinson’s disease , deep brain stimulation

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

Neural basis of communication (BaNCo) (Pascal Belin)

We use neuroimaging and machine learning techniques to investigate the neural mechanisms of communication in human and non-human primates.

Members

BELIN Pascal, CHAMINADEE Thierry, GIORDANO Bruno, TAKERKART Sylvain, CAGNA Bastien, RAUCHBAUER Birgit, TRAPEAU Régis, BODIN Clémentine, DAGENS Tom, WANG Qi. Total: 1 HDR.

Research axes

  • Neural bases of voice information processing
  • Functional architecture of auditory cortex
  • Neural bases of natural conversation

Techniques

  • Electrophysiology (in vivo, on animals)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Psychophysical tests
  • Brain imaging and stimulation – Man (fMRI, TMS…)
  • Brain imaging – Animal

Keywords

    Communication, multisensory perception, behavior, emotion, voice, face, stress, conditionning, fear, neuroimaging, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), magnetoencephalography (MEG)
Animal cognition and behavior - Computational neuroscience - Human cognition and behavior - Novel methods and technology development - Sensory systems

Cognitive Motor Control (CoMCo) (Thomas Brochier)

CoMCo uses complementary neurophysiological approaches in human and non-human primates to explore how neurons and brain structures coordinate their activity to prepare and control the execution of precise hand, arm and eye movements. CoMCo also seeks to determine how these dynamic processes adapt to pathological conditions as well as external disturbances applied to the brain or body.

Members

BROCHIER Thomas, DANION Frédéric, KILAVIK Bjørg, MALFAIT Nicole,  RIEHLE Alexa, BARTHELEMY Fréderic, DE HAAN Marcel, DURET Margaux, JAHANI Amirhossein, MATHEW James. Total: 5 HDRs.

Equipe CoMCo

Research axes

Research projects focus on 3 main areas.
● Dynamic neural processes for sensorimotor adaptation: We use functional connectivity measures to study how sensorimotor adaptation processes influence interregional communication at the macroscopic scale.
● The principles of coordination of movements between effectors: We seek in particular to analyze the neurophysiological processes involved in predictive mechanisms for hand-eye coordination.
● Sensorimotor network dynamics signatures at the neuronal level: We combine high density neuronal recordings in several areas or cortical layers to explore the nature of neuronal interactions during the performance of complex visual motor tasks.

Techniques

  • Electrophysiology (in vivo, on animals)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Psychophysical tests
  • Movement or posture analysis, electromyography (EMG)
  • Brain imaging and stimulation – Man (fMRI, TMS…)
  • Brain imaging and stimulation – Animal (monkey)
  • Electroencephalography (EEG)
  • Medical data analysis

Keywords

    Movement, neuronal coding, behavior, computational neuroscience, planning, action, learning, electroencephalography (EEG), cortex, magnetoencephalography (MEG), electromyography (EMG), functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), brain-machine interfaces, neuro-rehabilitation, hemiplegic patients
Animal cognition and behavior - Computational neuroscience - Disorders of the nervous system - Human cognition and behavior - Motor systems - Novel methods and technology development - Sensory systems

Live imaging of cell interactions in the normal and diseased brain (Franck Debarbieux)

The team characterizes in vivo at the cellular scale the dynamics of neuroinflammatory processes involved in mouse models of neuropathologies (brain tumors, multiple sclerosis, CNS trauma) and their consequences on neuronal activity and plasticity.

We develop, integrate and use innovative nonlinear optical technologies to image the dynamic cellular composition of the central nervous system and the calcium activity in neurons. Having established a triple fluorescent mouse model to simultaneously visualize neurons in blue, activated microglia in yellow and peripheral inflammatory cells in green (granulocytes/monocytes), simultaneous CARS (Coherent Anti-Stoke Raman Spectroscopy) microscopy gives us access to the endogenous contrast generated by myelin around axons. Genetically encoded GCAMP probes report intracellular calcium, while an original implanted glass window technique allows us to re-imagine the same region of interest on the same animal, over times ranging from minutes to several weeks.

These methods allow us to study the evolution of the CNS under control conditions and to evaluate the effect of anti-inflammatory treatment or genetic manipulations. Finally, we explore the impact of electrical stimulation of the pathological environment to modulate inflammation and promote tissue healing/repair.

Members

DEBARBIEUX Franck, ROUGON Geneviève, AMOUREUX Marie-Claude, CARAVAGNA Céline, BUTTIGIEG Emeline, COMPAGNONE Marion, EL WALY Bilal, HIVERT Bruno, KAUR Jaspreet, PELLETIER Florence, SOUBERAN Aurélie. Total: 2 HDRs.

Equipe ImaPath, INT

Research axes

  • Intravital multispectral two-photon microscopy
  • CARS microscopy
  • Neuroinflammation
  • Electrostimulable neuroprothèsis

Techniques

  • Cell culture
  • Molecular biology
  • Biochemistry
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Animal surgery, stereotaxy
  • Pharmacology
  • Movement or posture analysis, electromyography (EMG)
  • Brain imaging – Animal

Keywords

Spinal cord trauma, Experimental Autoimmune Encephalomyelitis (EAE), Glioblastoma, Oligodendrocyte, Microglia, Monocytes, Dendritic cells, Cellular differentiation, Carbon electrodes, PEDOT-PSS.

Disorders of the nervous system - Excitability, synaptic transmission, network functions - Novel methods and technology development - Sensory systems

Methods and Computational Anatomy (Olivier Coulon)

The MeCA team is an interdisciplinary research group whose scientific goal is the quantification and modelling of cortical variability and development, and their link with function and white matter connectivity, using mostly magnetic resonance imaging on human and non-human primates.

Specifically we aim at:

–          quantifying and modelling cortical variability and organization.

–          quantifying and modelling cortical development.

–          quantifying white matter properties and connectivity.

–          studying the link between anatomy, function, and connectivity.

We develop morphometry tools and apply them on large databases.

Members

COULON Olivier, AUZIAS Guillaume, LEFEVRE Julien, VELLY Lionel, BOHI Amine, KALTENMARK Irène, BODIN Clémentine, GIACOMINO Laura, PRON Alexandre.

Research axes

  • Cortical variability and organisation
  • Relationships between anatomy/connectivity/function
  • Development
  • Biomarkers of emergency pathologies

Techniques

  • Brain imaging and stimulation – Man (fMRI, TMS…)
  • Brain imaging – Animal
  • Medical data analysis

Keywords

Computational neuroscience, cortical anatomy, connectivity, morphometrics, MRI

Computational neuroscience - Development of the nervous system - Disorders of the nervous system - Motor systems - Novel methods and technology development - Sensory systems

Plasticity and Physio-pathology of rhythmics Motor networks (Frédéric Brocard)

We study the functional organization of neural circuits in the spinal cord both in development and in pathological conditions (i.e. spinal cord injury (SCI)). One of the other exciting challenge of the team relies on identifying the upstream mechanisms of the pathophysiology of spasticity to develop effective, tolerable and minimally invasive treatment. We use a broad technical approach involving electrophysiology, biochemistry, imaging, anatomy, optogenetics and genetics to address three major questions: What are the mechanisms underlying the pacemaker activities of the rythmogenic locomotor network ? How does the plateau properties emerge in motoneurons ? What are the anatomical and functional mechanisms underlying spasticity after SCI and how to transfer our findings into clinical applications at the bedside ?

Members

BROCARD Frédéric, BENSOUSSAN Laurent, BOS Rémi, BRAS Hélène, BROCARD Cécile, COQ Jacques Olivier, DELARQUE Alain, DURAND Jacques, KERZONCUF Marjorie, LIABEUF Sylvie, PEYRONNET-ROUX Julie, ROCHE Pierre-Hugues, SANCHEZ BRUALLA Irène,VERNEUIL Jérémy, VIEMARI Jean-Charles, VITON Jean-Michel. Total : 3 HDRs.

Research axes

Spinal cord neural networks and locomotion under normal and pathological conditions.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Movement or posture analysis, electromyography (EMG)

Keywords

Spinal cord, pacemaker, motoneuron, lesions, locomotion, spasticity.

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

Social Cognition across Lifespan and Pathologies (SCaLP) (Christine Deruelle)

Our research projects explore the developmental, behavioural and brain bases of social cognition and their dysfunctions in psychopathologies such as autism, Asperger syndrome and bipolar disorder

Members

DERUELLE Christine, ADIDA Marc, AUZIAS Guillaume, AZORIN Jean-Michel, BAT Flora, BROUSSE Marion, DA FONSECA David, POINSO François, POMIETTO Pascale, THIRION Sylvie, VIEILLARD Marine, PRON Alexandre. Total: 4 HDRs.

Research axes

  • Social cognition in neurodevelopmental disorders with atypical social behavior
  • Atypical social competences: autism and artificial agents
  • In search of cognitive and emotional markers of bipolar disorder
  • A proactive socio-emotional brain

Techniques

  • Psychophysical tests
  • Brain imaging and stimulation – Man (fMRI, TMS…)

Keywords

    Social interactions, social cognition, development, emotion, face, behavior, neuroimaging, autism, bipolar disorder, attention deficit disorder, cognitive therapy
Development of the nervous system - Disorders of the nervous system - Human cognition and behavior - Novel methods and technology development

Micro-RNA and social cognition (mirCOS) (Eduardo Gascon Gonzalo)

Our team focus is the deciphering the molecular basis of social behavior in physiology and in pathology (mainly in depression). We currently work on miRNAs to improve our understanding of social functions. We address these issues using a multidisciplinary approach (molecular biology, cell culture and animal models) and the latest technology in genome editing and single-cell sequencing.

Members

GASCON GONZALO Eduardo, BELZEAUX Raoul, BORGES-CORREIA Ana Maria, BOUCRAUT José, CACCOMO Elodie, IBRAHIM El Chérif, LEPOLARD Catherine, POPA Nathalia, JAOUEN Florence.  Total: 3 HDRs.

Research axes

  • Molecular basis of social behavior
  • Epigenetics in depression

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal surgery, stereotaxy
  • Animal behavior

Keywords

microRNA, epigenetics, Cas9, comportement, depression, animal models.

Animal cognition and behavior - Disorders of the nervous system - Human cognition and behavior - Novel methods and technology development

Spinal Cord and CSF Interface (Nicolas WANAVERBECQ)

Our team studies the properties of spinal neurons in contact with the CSF (CSF-cNs) and aims at demonstrating their function in the mammalian CNS under physiological and pathological conditions.

To answer this question, we are developing different transgenic mouse models that we study using a wide spectrum of complementary techniques (histology, electrophysiology, calcium imaging and optogenetics) and preparations (acute slices, ‘en bloc’ and in vivo preparation).

More recently, we are developing preparations in non-human primates and humans to study the properties of CSF-cNs.

Members

WANAVERBECQ Nicolas, TROUSLARD Jérôme, KASTNER Anne, SEDDIK Riad, JURCIC Nina. Total : 3 HDRs

Research axes

Physiological properties of neurons in contact with the CSF (CSF-cN) along the spinal cord central canal.
Anatomical and functional characterization of CSF-cNs connectivity in the spinal cord.
Demonstrate in vivo the physiological role of spinal CSF-cNs in mammals
Interaction between CSF-cNs and spinal niche stem cells to demonstrate their role in spinal cord repair processes.

Techniques

  • Molecular biology
  • Biochemistry (Western blot…)
  • Cell culture
  • Immunostaining, histology, flow cytometry
  • Microscopy (fluorescence, confocal, electronic…)
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Movement or posture analysis, electromyography (EMG)
  • Optogenetics

Keywords

Spinal cord, Ion channels and modulation, CSF interface, Motor activity, Spinal networks, Sensory system, Spinal cord injury and regeneration.

Excitability, synaptic transmission, network functions - Motor systems - Novel methods and technology development - Sensory systems

dynamic NEuronal OPerations in visual TOpographic maps ( NEOPTO) (Frédéric Chavane)

One of the key properties of sensory cortical areas is their organization into topographic maps. Along the visual system hierarchy, low-level features such as position and orientation, but also higher-level features, such as shape or movement, are represented topographically on the cortical surface. Thus, a local and oriented stimulus will activate precise cortical columns within the orientation and retinotopic maps.

However, under natural conditions, the local features composing the visual scene are numerous, dynamic and distributed at different spatio-temporal scales, sometimes generating ambiguous or illusory perceptions.

How such dynamic inputs are processed at different stages of the visual system to result in a robust and fast encoding of the visual scene? NeOpTo’s working hypothesis is that cortico-cortical interactions dynamically shape the processing and representation of visual stimuli within these maps. To test this hypothesis we use convergent approaches of experimental measurement of cortical activity at micro and mesoscopic scales, but also of technological and theoretical development. Understanding how the visual world is represented in cortical maps also has clinical consequences, for example to improve the functioning of retinal prostheses.

Members

CHAVANE Frédéric, DENIS Danièle, HOFFART Louis, MATONTI Frédéric, MULLER Lyle, VANZETTA Ivo, BERNARD Anaïs, BRUN Lucile, CHEMLA Sandrine, ROUX Sébastien, POULKOURAS Romanos. Total : 4 HDRs.

Research axes

  • Dynamical representations within and between cortical networks
  • Methods for multi-scale and multi-model imaging
  • Improving prosthetic vision with cortical imaging

Techniques

  • Calcium imaging
  • Electrophysiology (in vivo, on animals)
  • Animal surgery, stereotaxy
  • Animal behavior
  • Brain imaging – Animal

Key words

Sensory cortical areas, topographic maps, micro and mesoscopic scales.

 

Computational neuroscience - Disorders of the nervous system - Novel methods and technology development

AP2 (Bénédicte Dargent)

In neurons, the axonal initial segment (AIS) is the checkpoint between the somatodendritic and axonal compartments, ensuring final integration of dendritic inputs, generation of action potentials, and ultimately the maintenance of the neuronal polarity. The molecular organization of the AIS involves structural components like ankyrin G (ankG) and betaII and betaIV spectrin. Several convergent studies reveal that ANK3, the gene encoding for ankG, can be considered as a high psychiatric risk factor gene. The ankG scaffolding complex concentrates voltage-gated sodium channels Nav1, potassium channels Kv7.2/Kv7.3 cell adhesion molecules (NF-186 and NrCAM), and Kv1 in certain types of neurons. AIS organization also requires intracellular connections between ankG scaffold and the AIS microtubules through End Binding proteins and the actin cytoskeleton. While AIS ion channels support short-term plasticity, recent studies revealed that the entire AIS is capable of homeostatic plasticity through an activity–dependent change of its positioning along the proximal axon. The general objective of AP2 project consists in deciphering the complex interactions between AIS components for a better understanding of the mechanisms involved in AIS maintenance and integrity during development, and to explore potential defects of these mechanisms in the physiopathology of psychiatric disorders.

Members

DARGENT Bénédicte, TROUPLIN Virginie, ALORY Alysson. Total : 1 HDR.

Research axes

  • Deciphering the mechanism involved in AIS shape and positioning along the proximal axon in physiological and pathological situation.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, flow cytometry
  • Microscopy
  • Pharamacology

Key words

Axon initial segment, ankyrin G, ion channels, excitability, psychiatric disorders.

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