Modulation of epileptiform activity by three subgroups of GABAergic interneurons in mouse somatosensory cortex

Abstract

4-Aminopyridine (4-AP) induces ictal-like epileptiform discharges in a variety of brain regions. These events are associated with enhanced inhibitory and excitatory synaptic neurotransmission. The relative contribution of specific subclasses of GABAergic interneurons (INs) to epileptiform activity in the 4-AP model is not well characterized. We have used genetically encoded channelrhodopsin (ChR) and Archaerhodopsin (Arch) expression in parvalbumin (PV), somatostatin (SST) and vasoactive intestinal polypeptide (VIP) INs to investigate the role of interneuron subclasses in 4-AP-induced epileptiform discharges. Whole-cell patch-clamp recordings were obtained from L5 pyramidal cells (PYRs) in somatosensory cortex of 30-to-70-day old mice. In the presence of 100 µM 4-AP, photostimulation of ChR in PV and SST, but not VIP INs, evoked epileptiform discharges similar to spontaneous and electrically evoked events. Light activation of Arch in PV INs was more effective in reducing epileptiform activity compared to SST and VIP INs. Epileptiform discharges were evoked at offset of Arch induced hyperpolarizations in PV and SST interneurons but not VIP INs. PV and SST INs could both initiate and inhibit 4-AP-induced epileptiform activity in L5 PYRs. VIP INs did not contribute significantly to eliciting or inhibiting epileptiform discharges. These results suggest that subclasses of INs contribute differently to the initiation and modulation of epileptiform discharges in cortical networks.