Abstracts

Rationale: Following chemoconvulsant treatment, aberrant high-frequency oscillations, called fast ripples, are seen during the latent period (time between insult and spontaneous epilepsy). It has been hypothesized that fast ripples play an important role in epileptogenesis, perhaps by kindling the dentate gyrus. We sought to determine whether a perforant pathway stimulation (PPS)-based animal model of epilepsy also exhibits aberrant neuronal network activity in the dentate gyrus during the latent period.Methods: Male Sprague-Dawley rats (n = 4) were implanted bilaterally with stimulating electrodes in the perforant pathway and recording electrodes in the dorsal hippocampal granule cell layer. Freely moving animals received 8 h of PPS, which has been shown to have an average latency to spontaneous epilepsy of 21 days. Rats were then continuously monitored for both electrographic activity and behavior until the first spontaneous seizure. Results: Spontaneous, large-amplitude waveforms were recorded throughout the latent period. These events were single granule cell population spikes, which appeared to be evoked by aberrant input from the entorhinal cortex. This is evidenced by the fact that these unprovoked waveforms have nearly identical morphology to those evoked by low-frequency PPS. The spontaneous activity did not include high frequency oscillations.Conclusions: These data demonstrate that the dentate gyrus receives significant aberrant input from the entorhinal cortex throughout the latent period, following 8 h of PPS. These spontaneous events appear to 1) be a clear biomarker of epileptogenesis, and 2) further implicate entorhinal cortex dysfunction in epileptogenesis.