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 (Frédéric Chavane, Guillaume Masson)

Vision is a major sensory input for guiding our actions, perceiving our environment and con-ducting cognitive tasks. Yet the visual inputs that reach the brain represent a computational challenge: they are ambiguous, dynamical and segmented into a myriad of piecewise cues. Imagine, for example, that you have to visually track a moving object in rainy conditions and that this target disappears behind a large object for a while. Such an apparently easy task requires segregating the various motion signals in order to integrate the trajectory of the target and continuously track it with the gaze.

To overcome this problem, our visual system must combine sensory inputs with a priori knowledge at multiple spatial and temporal scales. Our research projects aim at elucidating the neural computations that meet these challenges. To do so, the InVIBE team develops multiple expertises involving behavioral studies in both humans and monkeys, electrophysiological and real-time optical imaging studies in behaving monkeys and Bayesian modeling approaches.

Members

CHAVANE Frédéric, MASSON Guillaume, BENVENUTI Giacomo, BOURRELLY Clara, CHEMLA Sandrine, DAMASSE Jean-Bernard, DENIS Danièle, GOFFART Laurent, HOFFART Louis, MADELAIN Laurent, MATONTI Frédéric, MESO Andrew, MONTAGNINI Anna, PERRINET Laurent, QUINET Julie, RIDINGS Bernard, ROUX Sébastien, SIMONCINI Claudio, TAOUALI Wahiba, VANZETTA Ivo, VIDAL Manuel. Total: 3 HDRs.

Research axes

  • to understand how visual motion  information is integrated, neurally represented and modulated for guiding the visual exploration and the buildup of percepts.
  • to investigate how these context-dependent dynamical representations are guiding, or conversely influenced by, goal-directed oculomotor behaviors (saccades, pursuit)
  • to understand how the visual inputs interact with dynamical and hierarchical inferences embodied in the early cortical stages to control visual motion integration.
  • to investigate cortical dynamics when a massive re-mapping of the inputs is caused by retinal lesions and testing in animal models (monkeys, rodents) the efficiency of retinal prostheses.

Techniques

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

Keywords

Visual motion perception, eye movements, visual attention, decision-making, behavior, cortex, local-global processing, visual psychophysics, computational neuroscience

Animal cognition and behavior - Computational neuroscience - Excitability, synaptic transmission, network functions - Human cognition and behavior - Novel methods and technology development - 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 in motivation and reward-related processes, both in normal and dysregulated behaviors, such as addiction, impulse control disorders or affective memory.

We are studying the effect of subthalamic nucleus subthalamic nucleus inactivation, using deep brain stimulation (DBS) on cocaine addiction in rodents and monkeys, as well as the role of this structure in reward-related processes and in impulse control, with brain imaging as well, in the monkey.

Among the research conducted in non-human primates, some address the role of basal ganglia in reinforcement learning and the neural basis of motivational processes, using electrophysiological recordings in awake animals.

The clinical approach combines behavioral and electrophysiological studies. We are performing electrophysiological recordings of subthalamic nucleus activity as well as functional imaging in post-operative Parkinson’s disease patients and studying the clinical effects of subthalamic nucleus stimulation on the motivational state of parkinsonian patients with or without impulse control disorders.

Members

BAUNEZ Christelle, APICELLA Paul, AZULAY Jean-Philippe, EUSEBIO Alexandre, GARCIA René, GIORLA Elodie, MARCHE Kevin, MONTANARI Christian, DEGOULET Mickaël, RAVEL Sabrina, TIRAN CAPPELLO Alix, WITJAS Tatiana, NACEF Jennifer, MARTEL Anne-Caroline. Total: 5 HDRs.

Techniques

  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Brain imaging and stimulation – Man (fMRI, TMS…)
  • Brain imaging – Animal
  • Optogenetics

Keywords

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

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

Neural basis of communication (Pascal Belin)

Verbal communication involving language is more evident; yet, 90% of all social interactions actually rely on non-verbal communication. Non-verbal communication involves the processing of information, other than language, crucial for life in society such as age, gender, identity and emotional expressions. The human brain has the extraordinary capacity of processing this information from multiple sensory sources.

Research projects developed in the BANCO team are principally focused on understanding the cerebral correlates/mechanisms underlying both verbal and non-verbal communication in its emotional and non-emotional aspects. We use a variety of complementary research methods to study the neural basis of communication in both human and non-human primates, such as functional and structural magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), electroencephalography (EEG), magnetoencephalography (MEG) and behavioral measurements.

Members

BELIN Pascal, AGLIERI Virginia, AUBERT-KHALFA Stéphanie, BOUKEZZI Sarah, ROUSSEAU Pierre-François, BODIN Clémentine. Total: 1 HDR.

Research axes

  • Perceiving vocal non-verbal information
  • The role of stress in social interactions

Techniques

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

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

Cognitive Motor Control (CoMCo) (Alexa Riehle / Thomas Brochier)

Our team integrates neurophysiological, behavioral and computational approaches to understand how cortical and spinal processes represent internal goals, predictions, learning mechanisms and contextual constraints, and how they are translated into motor plans and behaviors.

We do similar experiments in human and monkeys and assess various motor behaviors in terms of the dynamics of multi-joint arm reaches and object-related hand movements. In monkeys we record massively parallel single neuron activities and local field potentials (LFP) as well as intracranial EEG simultaneously in various cortical areas, from visual over parietal to motor areas.

In humans, we use neuroimaging (fMRI), transcranial magnetic stimulation (TMS), and neurophysiological techniques to record brain activity (EEG, MEG, intracranial EEG) and muscular activity (EMG, single motor unit activity) to investigate cognitive motor control processes.

Our experiments are interpreted in the framework of computational motor control and neuronal coding theories.

The design of such parallel studies is a novel approach, which results in a cross-fertilization of ideas. The study of the sensorimotor transformations from intention to action via planning is both an interpretable window into the operation of the cerebral cortex and an essential pre-requisite to progress in brain machine interface (BMI) technology and neuro-rehabilitation, especially in hemiplegic patients.

Members

RIEHLE Alexa, BROCHIER Thomas, DE HAAN Marcel, BROVELLI Andrea, KILAVIK Bjørg, MALFAIT Nicole, TORRECILLOS Flavie, DURET Margaux, DANION Fréderic, ALAYRANGUES Julie, BARTHELEMY Fréderic, BENSOUSSAN Laurent, DELARQUE Alain, JAHANI Amirhossein, MATHEW James,VITON Jean-Michel. Total: 4 HDRs.

Equipe CoMCo

Techniques

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

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 - Excitability, synaptic transmission, network functions - Human cognition and behavior - Motor systems - Novel methods and technology development

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

We are studying cell-cell interactions in the normal and diseased central nervous system. Many cell types interact in the diseased central nervous system (CNS) and synergistically control the evolution of pathologies. The dynamics of these interactions as well as their outcome are poorly known due to the lack of resolving non-invasive imaging methodologies.

We have set up two in vivo imaging modalities with different scales of spatial resolution, X-ray micro computed tomography (CT) and 2-photon (2P) microscopy, to visualize neural and immune cells as well as blood vessels in mouse models of central nervous system pathologies. The mastering of 2P in vivo imaging combined to the use of mouse models whose different cell populations shine in different colors allows simultaneous multicolor imaging as well as unlimited number of examinations of the same field of view. This opens the way to quantitative and correlative analysis of cell distributions and interactions in a truly physiological environment.

In collaboration with physicists, we validated a high resolution computed tomography (micro-CT) system, based on a new generation of detectors called Hybrid Pixel Detectors (HPD) to observe mouse soft tissues. We expect to implement a multicolor CT scanner to obtain complementary information on the same animals previously imaged with the 2P microscope at a local scale. Although offering far less resolution than 2P microscopy, CT scan presents the complementary advantage of exploring the whole body. These technologies allow the collection of large amounts of data from a single animal, hence reducing the number of animals engaged in an experimental study and improving the significance of the results.

Members

DEBARBIEUX Franck, ROUGON Geneviève, AMOUREUX Marie-Claude, JAOUEN Alexandre, LAMASSE Lisa, MEUNIER Cécile, RICARD Clément, TCHOGHANDJIAN Aurélie, CARAVAGNA Céline. Total: 2 HDRs.

Equipe ImaPath, INT

Techniques

  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal surgery, stereotaxy
  • Pharmacology
  • Brain imaging – Animal

Keywords

    Imaging, biphoton microscopy, CT scanner, tumor, glioblastoma, spinal cord lesions, blood vessels, neurons, inflammation, cellular interactions, multiple sclerosis
Disorders of the nervous system - Novel methods and technology development

Methods and Computational Anatomy (Olivier Coulon)

MeCA is an interdisciplinary research group established by the Institut de Neurosciences de La Timone and the Laboratoire des Sciences de l’Information et des Systèmes, combining their skills in basic and clinical neuroscience and data processing to better understand the organization and operation of normal and pathological brain. More specifically, the object of interest is mostly the cerebral cortex and the observation instrument is magnetic resonance imaging (MRI). The scientific goals of MeCA are the quantification and modelization of cortical variability and development, the understanding of the link between cortical macro-anatomy and functional orgnization, and the development of new quantitative morphometry methods and their validation on large normal and pathological databases.

Members

Permanent: COULON Olivier, LEFEVRE Julien, BELIN Pascal, DERUELLE Christine, VELLY Lionel. Total : 3 HDRs.

Non permanent: AUZIAS Guillaume, PEPE Antonietta, RABIEI Hamed, THIEBAUT Lucie, BRUN Lucile, PRON Alexandre.

Research axes

  • Inter-subject matching and population studies.
  • Cortical morphometry: looking for biomarkers associated with developmental disorders or functional specificities.
  • Modeling the organization and variability of the cerebral cortex
  • Correlation between cortical macro-anatomy in MRI and the underlying functional, or even architectural, organization
  • Models of normal and pathological cortical development

Techniques

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

Keywords

    neuroimaging, magnetic resonance imaging (MRI), cortex, cortical variability, cortical macroanatomy, neurodevelopmental pathologies, development, modelization, structure-function relationships
Computational neuroscience - Development of the nervous system - Disorders of the nervous system - Novel methods and technology development

Motor neuron disease Modeling and Therapy (Georg Haase)

In the aging populations of Western countries, one out of four persons is at risk for a neurodegenerative disease. Amyotrophic lateral sclerosis (ALS) is a particularly devastating and always fatal disorder without effective therapies. ALS affects motor neurons in cerebral cortex, brainstem and spinal cord, leading to progressive muscle atrophy and paralysis. While most forms of ALS appear sporadically, about 10-20 % are familial and caused by mutations in genes encoding diverse proteins. According to studies in mutant mice, motor neuron degeneration first manifests far distally at the neuromuscular synapse with loss of synaptic vesicles and axon retraction but is initiated in the cell body and modulated by neighboring astrocytes and microglia. Our team hypothesizes that the Golgi apparatus may link peripheral manifestation, central initiation and neuron/glia-interactions in ALS.

In order to test the hypothesis, the team pursues the following specific aims :

  • To investigate how mutations in ALS genes trigger Golgi pathology, endosome dysfunction and synaptic vesicle loss in motor neurons.
  • To dissect out the mechanisms converging from Golgi dysfunction to cell death and axon degeneration.
  • To identify such pathological changes in motor neurons from human ALS patients.
  • To use this knowledge for the development of new experimental therapies.

Members

Georg HAASE, Gilbert BAILLAT, Sébastien SCHALLER. Total: 1 HDR.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture & viral and non-viral gene transfer
  • Immunostaining, histology, or flow cytometry, FACS
  • Microscopy
  • Animal surgery
  • Bioinformatics

Keywords

    Neurodegenerative diseases, amyotrophic lateral sclerosis, mutations, motor neurons, microglia, astrocytes, Golgi apparatus, endosome, synaptic vesicles, apoptosis, therapy, neurotrophic factors
Disorders of the nervous system - Motor systems

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

Our team aims at exploring the plasticity of rhythmic motor (locomotor and respiratory) networks both during development and in pathological conditions (spinal cord injury, prenatal exposure to toxicological factors). The scope of our studies spans from rodents to humans.

Members

BROCARD Frédéric, BAILLAT Gilbert, BELLOT Blandine, BRAS Hélène, BROCARD Cécile, CAYETANOT Florence, COQ Jacques Olivier, COULON Patrice, DURAND Jacques, GOURMAND Laetitia, LIABEUF Sylvie, PEYRONNET -ROUX Julie, PLANTIER Vanessa, ROCHE Pierre-Hugues, SANCHEZ BRUALLA Irène, VIEMARI Jean-Charles. Total: 5 HDRs.

Research axes

  • Plasticity of neuronal and network properties following spinal cord injury (SCI)
  • Activity-dependent modulation of neuronal and network properties
  • Dysfunction of motor development

Techniques

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

Keywords

    Motricity, locomotion, respiration, spinal cord, networks, development, motor neurons, interneurons, spasticity
Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Motor systems - Sleep, autonomic and neuroendocrine systems

Social Cognition across Lifespan and Pathologies (Christine Deruelle)

Social interactions affect every aspect of our lives and adaptive social behavior is essential for individual as well as societal functioning. Human brains and minds are shaped, and normally function, in continuous interaction with other people.

We integrate expertise from cognitive and clinical neuroscience, experimental psychology and advanced brain imaging techniques, to explore the behavioral and cerebral basis of natural social cognition and its dysfunction in neurodevelopmental disorders such as autism, ADHD, bipolar disorders and schizophrenia.

Our research involves the use of distinct but complementary methodological approaches: behavioral measurements, structural and functional MR imaging techniques (fMRI, DTI), and electroencephalography (EEG).

Members

DERUELLE Christine, ADIDA Marc, AUZIAS Guillaume, AZORIN Jean-Michel, BAT-PITAULT Flora, BRUN Lucile, CHAMINADE Thierry, DA FONSECA David, LESCALIER Lauriane, MANCINI Josette, POINSO François, POMIETTO Pascale, SILVA Catarina, , VIEILLARD Marine, WICKER Bruno, Wolfe Farah. 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…)
  • Electroencephalography (EEG)

Keywords

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

Micro-RNA and social cognition (Eduardo Gascon)

Brain evolution and the acquisition of superior brain functions are thought to rely on increasingly complex patterns of gene expression. Non-coding RNAs (ncRNAs) play an essential role in this process.

MicroRNAS (miRNAs) are short ncRNAs acting as post-transcriptional regulators of gene expression. Although accumulating evidence indicates that miRNAs might be essential for complex brain functions, the relationship between microRNA regulation and the specification of behavior is only beginning to be explored.

Using age-dependent decline of brain function, we seek:

  • To identify miRNAs involved in the molecular control of specific domains of mouse behavior (namely social and motor behaviors) as well as the neuronal networks implicated in those behaviors.
  • To investigate the mechanisms regulated by miRNAs at the molecular (i.e. downstream targets), cellular (i.e. morphological changes in dendrites/axons) and electrophysiological (i.e. synaptic plasticity) levels.
  • To study the molecular pathways by which aging affects miRNA homeostasis.

Members

Eduardo Gascon. Total: 1 HDR (under way).

Research axes

  • identifying miRNA changes in the aging brain
  • exploring miRNA activity in the living brain
  • generating genome-editing tools for in vivo inactivation of brain miRNAs
  • elucidating mechanisms regulating miRNA processing

Techniques

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

Keywords

    Micro-RNA, molecular pathways, neuronal networks, mouse behavior, aging.
Animal cognition and behavior - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Novel methods and technology development
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