Kelley, MR; Cardarelli, RA; Smalley, JL; Ollerhead, TA; Andrew, PM; Brandon, NJ; Deeb, TZ; Kelley, MR; Cardarelli, RA; Smalley, JL; Ollerhead, TA; Andrew, PM; Brandon, NJ; Deeb, TZ; Moss, SJ; - view fewer (2018) Locally Reducing KCC2 Activity in the Hippocampus is Sufficient to Induce Temporal Lobe Epilepsy. EBioMedicine , 32 pp. 62-71. 10.1016/j.ebiom.2018.05.029.

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Abstract

Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy, believed to arise in part from compromised 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 in mTLE patients and animal models of epilepsy. To test if reductions of KCC2 activity directly contribute to the pathophysiology of mTLE, 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.

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