PhysioNet

(Physiology & Physiopathology of Brain Networks Group)


Our principal objective is to understand how physiological and pathological behaviors emerge from the organization and the reorganization of the underlying neuronal architecture. The group’s research is structured around six themes:

  • Cell/network/whole brain dynamics and learning in physiological and pathological conditions (in epilepsy and Alzheimer)

  • Mechanisms leading to the construction of an epileptic brain

  • Anatomo-functional organization of normal and epileptic networks

  • Dynamics of brain stem neuronal networks and SUDEP mechanisms

  • Coupling between metabolism, chloride homeostasis and cell/network function

  • Development and testing of technological tools, mostly based on organic electronics, to measure and control brain activity

 

PHYSIONET TEAM 

TEAM LEAD

Christophe BERNARD

DR, INSERM

EMAIL: christophe.bernard@univ-amu.fr
PHONE: +33 4 91 29 98 06

 

Christophe Bernard graduated as an Engineer in 1984 at the Ecole Centrale Paris, then completed a PhD in Neuroscience at Paris VI University in 1990, did his post-doctoral training at the University of Southampton between 1991-4 and a sabbatical period in 1999-2001 at Baylor College of Medicine (Houston, TX). Since 2001, he’s held the Group Leader position (DR, INSERM) as well as group leader for PhysioNet. He previously was a Reviewing Editor of Science and the Journal of Neuroscience, and is now Editor in Chief of the SfN journal eNeuro.

Christophe Bernard was awarded the Michael Prize on epilepsy research in 2007 (most prestigious international prize on epilepsy) and the Felix Innovation Prize in 2013 for the development of a novel organic transistor to record brain activity. His main interest is to understand the mechanisms underlying the construction of an epileptic brain as well as the mechanisms underlying seizure genesis and propagation, focusing on Temporal Lobe Epilepsy (TLE). These research themes are being addressed using a wide array of disciplines, including electron microscopy, morphology, immunohistochemistry, in vitro and in vivo electrophysiology, behavior, mathematics and modeling. Over the years, using experimental models of TLE, our group has developed a solid international reputation, in the field of epilepsy.
Find out more at my Research Gate page.

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PHYSIONET NEWS 


PHYSIONET RESEARCH 

Our principal objective is to understand how physiological and pathological behaviors emerge from the organization / reorganization of the underlying neuronal architecture. The team’s research is structured around six themes:

1. Cell and Network Dynamics in physiology and pathology (PI: C. Bernard, DR1 INSERM, P. Quilichini, Postdoc, AMU)

Cognitive processes depend upon the activity of distributed networks in the brain. We have two goals:

(1) Understand the fundamental mechanisms underlying the communication between brains regions controlling memory processes. We aim to determine how cortico-thalamo-hippocampal networks exchange information to encode and consolidate.

(2) Understand how these physiological rules are modified in different pathological conditions (Epilepsy and Alzheimer). We aim to determine the mechanisms of vulnerability to epilepsy induced by stress as well as the co-morbidities such as depression, cognitive deficits (memory).

We use a multi-disciplinary approach in naïve animals (rats and mice), experimental models of epilepsy (pilocarpine and kainite models) and Alzheimer (APPNL-G-F transgenic mice) in which we couple in vivo multisite recordings with silicon probes, behavior and state of the art signal processing.


Click image to enlarge.

2. Cell and Network Dynamics and new technologies: Virtual mouse brain and organic electrodes (PI: C. Bernard, DR1 INSERM)


Using mathematical and modeling approaches in close collaboration with the TNG team of V. Jirsa, we are studying the basic mechanisms of seizure genesis and propagation across species. In addition, we also use a whole brain approach with the virtualization of individual mouse brains (The Virtual Mouse Brain) to study structure/function relationships in health and disease.
One part of our activity is devoted to design new in vivo recording devices. This is done in close collaboration with Ecole des Mines de St Etienne in Gardanne (Rod O’Connor) and Cambridge University (G. Malliaras). We are experimenting multimodal organic probes, to measure simultaneously electrical signals and any enzymatic activity, as well as electronic pump for the local delivery of drugs to control brain activity.





3. Structural and Functional Properties of Epileptogenic Networks in Mesial Temporal Lobe Epilepsies (PI: M. Esclapez, DR2 INSERM)

Click image to enlarge.

Mesial temporal lobe epilepsies (MTLEs) are refractory to pharmacological treatment. The most effective treatment for these epilepsies remains surgery, which is only effective in 60% of cases. This impasse is partly due to our partial understanding of the epileptogenic network characterizing these epilepsies. Electro-clinical studies provide evidence that these epilepsies are network diseases: The epileptogenic zone is a multi-structural network where the emergence of seizures requires not only the hyperactivity of neuronal populations but also the co-activation (synchronization of the activity) of the different limbic cortexes within the temporal lobe including the hippocampus, amygdala and entorhinal cortex. This led us to develop a research program to determine the structural and functional organization of the limbic neuronal networks, including sub cortical structures responsible of this paroxysmal activities and synchronization in the epilepsies. For this research, we combine innovative structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization, tissue clarification) and imaging (light, electron and confocal microscopy) with optogenetic and electrophysiological recording performed in rodent models of MTLE including several strains of transgenic mice as illustrated below.




4. Neuronal Network Dynamics and SUDEP (Sudden Death in EPilepsy) mechanisms (PI: C. Gestreau, MC AMU)


Using a state-of-the-art in vitro preparation, we are investigating the dynamics of brain stem networks involved in respiration, in particular in the context of sudden death in epilepsy (SUDEP).




5. Metabolism Chloride homeostasis and cell function coupling in Neural Networks (PIs: Y. Zilberter, DR2 INSERM; P. Brest, Emeritus INSERM)


One principal question is how neuronal activity depends on energy metabolism. Many neurodegenerative diseases are characterized by metabolic stress. We suggest that metabolic deficits result in a pathological cycle of events, which contribute to the development of neurodegenerative diseases. A key prediction of our hypothesis is that the strategic compensation of energy deficiency could interrupt this pathological spiral and could provide a rational therapeutic option, which addresses the cause of the neurodegenerative diseases and not just the symptoms.
We are also using state-of-the-art tools to control the activity of Cl channels with light, and measure intracellular chloride.




6. Neuroengineery (PI: A. Williamson, CR INSERM, ERC Starting Grant 2016)


We combine advances in neuroscience with advances in engineering to reach goals which neither engineering nor neuroscience could reach alone. Our research is therefore highly cross-disciplinary and boasts: - Neuroscientific expertise, particularly focused on in vivo rodent models of neurodegenerative disease; - Engineering expertise, particularly focused on flexible polymer electronics.
We combine our models of neurodegenerative disease with our flexible polymer devices, specifically: 
1) to better understand the fundamental neurodegenerative process; 
2) to improve the technology used in the treatment of the disease.