Abstracts

Rationale: Epilepsy is a dynamic disease, and the characteristics (intensity, duration, frequency) of seizures can vary from one seizure to the next. Numerous features of the temporal variation in epileptic activity have been identified in EEG recordings and have been linked to the ictogenic process. Interictal population spikes (IS) are one useful criterion for the diagnosis of epilepsy in EEG recordings, but their role in development of seizure onset is not fully known. To better understand the mechanistic role ISs have in the development of epilepsy we correlated in vivo the relationship of single neuron activity (pyramidal cells and interneurons), with the occurrence of ISs in the hippocampus of rats with stimulation induced temporal lobe epilepsy.Methods: Microelectrode arrays were used to simultaneously record single unit activity (SUA) and local field potentials (LFP) from the CA3 region of rats. After inducing status epilepticus, the SUA and LFPs were continuously monitored until 10 seizures had been recorded. Once spontaneous seizures began, they occurred consistently with at least two seizures per week. The shortest period of time between seizures was 10 hr. This method allowed us to monitor and assess the changes in neuronal activity as the epileptic condition developed. Using off line spike sorting, the firing times for interneurons, pyramidal cells, and ISs were identified for the 1.5 hr prior to each seizure onset.Results: Statistically, the firing rate of pyramidal cells showed greatest modulation 170 s prior to seizure onset, but there was little change in this firing rate through the temporal progression of the 10 seizures. Interneurons also showed modulation 490 s prior to seizure onset, but they also showed an overall increase in firing rate as the number of seizures progressed. The largest increases began after seizure 5. Similarly, the number of interictal spikes prior to seizure onset increased with each consecutive seizure until two seizures occurred within a 24 hr period. Leading up to this seizure, 102 ISs were identified. After this seizure, the number of interictal spikes decreased to around 50 ISs in 1.5 hr until another set of two seizures occurred within 24 hr of each other. Again, a large increase in the number of ISs was observed before the second seizure, with 217 occurring in the 1.5 hr before seizure onset.Conclusions: The progressive increase in interneuron firing rates with each successive seizure suggest that interneurons might be more involved with the development of temporal lobe ictogenesis as compared to pyramidal cells in this animal model. While pyramidal cells exhibited a relatively flat distribution of firing rates across seizures, the temporal correlation of increases between interneurons and ISs may indicate that the two processes are linked. This work presents a multiscale approach for relating the fine timing relationships of neuronal and population activity at the onset of seizure. (The Children's Miracle Network, University of Florida Alumni Fellowship, B.J. and Eve Wilder Epilepsy Research Endowment)