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.