TLE is the most common form of human epilepsy and a major health burden, as 30% of TLE patients are refractory to currently available pharmacotherapies. The overarching hypothesis of this project is that ectopic synaptic KARs in the DG markedly contribute to epileptiform activity in patients with TLE (Péret et al, 2014; Crépel and Mulle, 2015). This implies that ectopic KARs represent a promising new therapeutic target for TLE displaying pharmacoresistance. In collaboration with Valérie Crépel (Inserm, Marseille) and with the company Corlieve Therapeutics, our central goal is to design and validate parallel strategies to target aberrant synaptic KARs, and moreover to extend our current understanding of a pathological role of KARs in the hippocampus to studies in neocortical circuits (including the IC). This is performed in particular in organotypic cultures derived from human surgical resections, provided by Guillaume Penchet, a neurosurgeon at the Bordeaux University Hospital.