Interneuron subtype specific activation of mGluR1/5 during epileptiform activity in hippocampus

P>Purpose: Specific inhibitory interneurons in area CA1 of the hippocampus, notably those located in stratum oriens-alveus (O/A-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 (mGluR1/5), which have generally proconvulsive actions and activate prominent cationic currents and calcium responses specifically in O/A-INs. Methods: In this study, we examine the role of mGluR1/5 in interneurons during epileptiform activity using whole-cell recordings from CA1 O/A-INs and selective antagonists of mGluR1 alpha (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 O/A-INs than in interneurons located at the border of strata radiatum and lacunosum/moleculare (R/LM-INs). In addition, mGluR1 and mGluR5 significantly contributed to epileptiform responses in O/A-INs but not in R/LM-INs. Epileptiform burst discharges in O/A-INs were partly dependent on mGluR5. PDs and associated postsynaptic currents were dependent on both mGluR1 alpha and mGluR5. These receptors contributed differently to postsynaptic currents underlying PDs, with mGluR5 contributing to the fast and slow components and mGluR1 alpha to the slow component. Discussion: These findings support interneuron subtype-specific activation and differential contributions of mGluR1 alpha and mGluR5 to epileptiform activity in O/A-INs, which could be important for their selective vulnerability in TLE.