Repetitive Perforant-Path Stimulation Induces Epileptiform Bursts

46 47 The epileptic hippocampus has an enhanced propensity for seizure generation, but how 48 spontaneous seizures start is poorly understood. Using whole-cell and field-potential recordings, 49 this study explored whether repetitive perforant-path stimulation at physiological frequencies 50 could induce epileptiform bursts in dentate gyrus minislices from rats with kainate-induced 51 epilepsy. Control slices from saline-treated rats responded to single perforant-path stimulation 52 with an EPSP and a single population spike in normal medium, and repetitive stimulation at 53 different frequencies (0.1, 1, 2, 5, 10 Hz) did not cause significant increases in the responses. 54 Most minislices (82%) from rats with kainate-induced epilepsy also responded to single 55 perforant-path stimulation with an EPSP and a single population spike/action potential, but some 56 slices (18%) had a more robust response with a prolonged duration and negative DC shift or 57 responses with 2-3 population spikes. Repetitive perforant-path stimulation at 5-10 Hz, however, 58 transformed the single-spike responses into epileptiform bursts with multiple spikes in half 59 (52%) of the slices, while lower frequency (e.g., ≤1 Hz) stimulation failed to produce these 60 changes. The emergence of epileptiform bursts was consistently associated with a negative field61 potential DC shift and membrane depolarization. The results suggest that compared to the 62 controls, the “gate” function of the dentate gyrus is compromised in rats with kainate-induced 63 epilepsy, and epileptiform bursts (but not full-length seizure events) can be induced in minislices 64 by repetitive synaptic stimulation at physiological frequencies in the range of hippocampal theta 65 rhythm (i.e., 5-10 Hz). 66 67