Abstracts

Rationale: What causes the termination of seizures remains an unsolved problem. Various hypotheses have been proposed, including energy depletion, active inhibitory processes, high extracellular K accumulation, depolarizing block of neurons, etc. We examined the excitability of one afferent pathway to the hippocampus during the transition to the postictal period.Methods: Epilepsy was induced by an 8 hour unilateral perforant path stimulation paradigm which, after a short latent period, results in about half the animals becoming epileptic with 1-3 seizures per week. EEG activity was recorded continuously and bilaterally from hippocampal DG (2Khz, 600 and 0.1Hz filters). After an animal exhibited spontaneous seizures (1-2 weeks), we began unilateral paired pulse stimulation of the perforant path. One pair of pulses (PPS, 20V, 20ms interpulse interval) was given every hour to measure baseline response. When a seizure was detected by online monitoring, PPS was given every second for the first 50 seconds and then every 10 seconds for 5 minutes. The periseizure data were recorded at 28 KHz (8K, 0.1Hz filters). We examined spontaneous and evoked population spikes and evoked fEPSP timing and size. We considered seizure to end when the EEG activity transitioned from high-amplitude activity to a period where the EEG amplitude and power were lower than immediately before the seizure started. Results: During the seizure, evoked pop spike amplitude was significantly smaller than baseline values but multiple pop spikes were often evoked with one stimulation pulse. In addition, pop spikes appeared on smaller fEPSPs. These observations suggest an increased DG excitability. Throughout the seizures, spontaneous pop spikes were present with very variable amplitudes. Paired pulse inhibition of fEPSP was lost. Paired pulse inhibition of pop spikes remained present throughout the seizures but was reduced compared to baseline and occasionally converted to paired pulse facilitation. Towards the end of the seizure, evoked fEPSPs and pop spikes increased in amplitude to about 50-80% of baseline values and stayed at that amplitude during the postictal quiet period in the EEG. Paired pulse inhibition was also restored toward baseline. Over the course of the next two to three hours all measures returned to baseline values.Conclusions: The paired pulse stimulation data demonstrate hyperexcitability of DG granule cells throughout seizures, even in the presence of reduced synaptic drive. As the seizure terminated, paired pulse effectiveness was returning toward baseline and during the postictal quiet period the DG was very responsive to synaptic input. Full responsiveness took several hours. Thus the transition from seizure to non-seizure state is not due to a failure of perforant path drive or DG excitability. Supported by NIH Grant NS 41811.