Effect of Interictal Spikes on Single‐Cell Firing Patterns in the Hippocampus

Abstract

The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner.