title: 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).
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Shao
authors.forename: F Edward
authors.initials: FE
authors.lastname: Dudek
mesh_terms: D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks; D018891:Dentate Gyrus / Q000503:physiopathology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D007608:Kainic Acid; D008297:Male; D019580:Perforant Pathway / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007608:Kainic Acid