Repetitive Perforant-Path Stimulation Induces Epileptiform Bursts in Minislices of Dentate Gyrus From Rats With Kainate-Induced Epilepsy

Abstract

The epileptic hippocampus has an enhanced propensity for seizure generation, but how spontaneous seizures start is poorly understood. Using whole cell and field-potential recordings, this study explored whether repetitive perforant-path stimulation at physiological frequencies could induce epileptiform bursts in dentate gyrus minislices from rats with kainate-induced epilepsy. Control slices from saline-treated rats responded to single perforant-path stimulation with an excitatory postsynaptic potential (EPSP) and a single population spike in normal medium, and repetitive stimulation at different frequencies (0.1, 1, 2, 5, 10 Hz) did not cause significant increases in the responses. Most minislices (82%) from rats with kainate-induced epilepsy also responded to single perforant-path stimulation with an EPSP and a single population spike/action potential, but some slices (18%) had a more robust response with a prolonged duration and negative DC shift or responses with two to three population spikes. Repetitive perforant-path stimulation at 5-10 Hz, however, transformed the single-spike responses into epileptiform bursts with multiple spikes in half (52%) of the slices, while lower frequency (e.g., ≤ 1 Hz) stimulation failed to produce these changes. The emergence of epileptiform bursts was consistently associated with a negative field-potential DC shift and membrane depolarization. The results suggest that compared with the controls, the "gate" function of the dentate gyrus is compromised in rats with kainate-induced epilepsy, and epileptiform bursts (but not full-length seizure events) can be induced in minislices by repetitive synaptic stimulation at physiological frequencies in the range of hippocampal theta rhythm (i.e., 5-10 Hz).