CRNL conference of Vincent Magloire - Harnessing interneurons to treat focal epilepsy

Focal seizures are widely considered to arise from a disturbance of the excitation/inhibition balance, and in particular a failure of the GABAergic inhibitory system. In this context, interventions that focus on enhancing GABAergic interneuron activity hold great promise for preventing seizure initiation and propagation. Recent work focusing on parvalbumin-positive and somatostatin-positive interneurons has shown that inhibition mediated by these populations is too weak to suppress seizures effectively. In contrast, neurogliaform (NGF) cells, if appropriately recruited, could be much more effective, due to their high density of GABA release sites and unique signalling via “volume transmission”.

I will discuss the role of different interneurons during seizures and how we could harness their inhibitory power to prevent network hyperexcitability. I am using in vitro and in vivo electrophysiology combined with either closed-loop optogenetic manipulation of interneurons or two-photon imaging to uncover how GABAergic transmission fails in epilepsy and to attempt to rescue it.