Abstracts

RATIONALE: Electrical stimulation can abort afterdischarges in human subjects with refractory seizures undergoing cortical mapping (Lesser et al. 2000). We wished to determine if this phenomenon is due to activation of afferent excitatory pathways leading to overdepolarization of neurons and a reduction in their excitability. METHODS: Spontaneous epileptiform discharges were induced in the hippocampal CA3 and CA1 regions of brain slices from young Sprague-Dawley rats using 4-aminopyridine (final concentration, 50 ?M). Bursts of single or rhythmic repetitive epileptiform discharges appeared spontaneously and could also be triggered by single brief electrical stimuli (10 ?s duration, 4 mA intensity) applied to the mossy fiber and Schaffer collateral inputs to the CA3 and CA1 regions, respectively. A second electrical stimulus (ES) was applied through the stimulating electrode at various times after the onset of the epileptiform discharge or at a fixed rate (1-7/sec). RESULTS: One thousand instances were evaluated where ES was applied during a run of epileptiform discharges. Of these, 216 were applied during the afterdischarge per se; in the others, the ES was applied during a gap in a run of discharges. When the ES was applied during a gap, a field EPSP response was invariably evoked. ES did not terminate the epileptiform activity regardless of when it was applied during the afterdischarges. CONCLUSIONS: Afferent excitatory stimuli, as a model of excitation overdrive, applied during an epileptiform discharge in rat hippocampus did not terminate the discharge using the above parameters. We are investigating the effectiveness of alternate stimulation parameters, as well as different paradigms, such as activation of local inhibitory hippocampal pathways, in terminating induced rhythmic repetitive epileptiform discharges.