Objective This proposal focuses on a human disease: epilepsy of the temporal lobe. This syndrome has a relatively stereotyped history. Focal seizures emerge, with a delay of several years in the human, after an initial insult that results in neuronal death. We will use physiology, imaging, anatomy and transcriptomic techniques to ask how an epileptic brain emerges, to define different neuronal cell types in the basal epileptic state and to examine factors associated with the paroxysmal transition to a seizure. Specifically we will ask whether a loss of cholesterol homeostasis is involved in the initial sclerotic neuronal death. We will ask whether proteoglycans deposited in the extracellular space as a generalised wound healing response force the establishment of aberrant synaptic contacts and so facilitate the slow process of epileptogenesis. We will then study the basal state of an epileptic brain. We will establish the physiology, anatomy, connectivity and transcriptome of functionally distinct neurons defined by different contributions to epileptiform activities in human epileptic brain slices. Finally we will seek to establish what sudden changes in field potential, ionic homeostasis, cellular firing and synaptic interactions are associated with the paroxysmal moment of transition to seizure. Fields of science medical and health sciencesbasic medicineneurologyepilepsymedical and health sciencesbasic medicineanatomy and morphologyhumanitieshistory and archaeologyhistorymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Call for proposal ERC-2012-ADG_20120314 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE EU contribution € 1 985 057,00 Address BOULEVARD DE L'HOPITAL 47 75013 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Richard Miles (Dr.) Administrative Contact Alexandra Auffret (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE France EU contribution € 1 985 057,00 Address BOULEVARD DE L'HOPITAL 47 75013 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Richard Miles (Dr.) Administrative Contact Alexandra Auffret (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
