Interneuron subtype specific activation of mGluR15 during epileptiform activity in hippocampus

Abstract

Purpose: Specific inhibitory interneurons in area CA1 of the hippocampus, notably those located in stratum oriens-alveus (OA-INs), are selectively vulnerable in patients and animal models of temporal lobe epilepsy (TLE). The excitotoxic mechanisms underlying the selective vulnerability of interneurons have not been identified but could involve group I metabotropic glutamate receptor subtypes (mGluR15), which have generally proconvulsive actions and activate prominent cationic currents and calcium responses specifically in OA-INs. Methods: In this study, we examine the role of mGluR15 in interneurons during epileptiform activity using whole-cell recordings from CA1 OA-INs and selective antagonists of mGluR1 (LY367385) and mGluR5 (MPEP) in a disinhibited rat hippocampal slice model of epileptiform activity. Results: Our data indicate more prominent epileptiform burst discharges and paroxysmal depolarizations (PDs) in OA-INs than in interneurons located at the border of strata radiatum and lacunosummoleculare (RLM-INs). In addition, mGluR1 and mGluR5 significantly contributed to epileptiform responses in OA-INs but not in RLM-INs. Epileptiform burst discharges in OA-INs were partly dependent on mGluR5. PDs and associated postsynaptic currents were dependent on both mGluR1 and mGluR5. These receptors contributed differently to postsynaptic currents underlying PDs, with mGluR5 contributing to the fast and slow components and mGluR1 to the slow component. Discussion: These findings support interneuron subtype-specific activation and differential contributions of mGluR1 and mGluR5 to epileptiform activity in OA-INs, which could be important for their selective vulnerability in TLE. © 2010 International League Against Epilepsy.