Locally Reducing KCC2 Activity in the Hippocampus is Sufficient to Induce Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (mTLE) is themost common form of epilepsy, believed to arise in part fromcompromised GABAergic inhibition. The neuronal specific K+/Cl- co-transporter 2 (KCC2) is a critical determinant of the efficacy of GABAergic inhibition and deficits in its activity are observed inmTLE patients and animalmodels of epilepsy. To test if reductions of KCC2 activity directly contribute to the pathophysiology ofmTLE, we locally ablated KCC2 expression in a subset of principal neurons within the adult hippocampus. Deletion of KCC2 resulted in compromised GABAergic inhibition and the development of spontaneous, recurrent generalized seizures. Moreover, local ablation of KCC2 activity resulted in hippocampal sclerosis, a key pathological change seen in mTLE. Collectively, our results demonstrate that local deficits in KCC2 activity within the hippocampus are sufficient to precipitate mTLE. (C) 2018 The Authors. Published by Elsevier B.V.