Abstracts

Dentate EEG spikes (DES) are large amplitude, short duration, spontaneous field potentials in the dentate gyrus that are generated by the synchronous discharge of layer II neurons in entorhinal cortex. Previous studies in anesthetized animals have shown that DES are more frequent and larger in amplitude in models of temporal lobe epilepsy. However, the role of DES in the generation of spontaneous seizures is unclear. Field potentials and multiple, single units were recorded from the granule cell layer of dentate gyrus in awake, freely-moving rats: 13 sessions in 3 epileptic, pilocarpine-treated rats and 4 sessions in 2 control rats. In epileptic rats, seizures were confirmed by behavior, and onset was identified electrographically as the earliest of four measures: one subjective (i.e., [quot]by eye[quot]) and three objective (i.e., by computer). DES were identified by spontaneous, large amplitude ([gt]2 mV), short duration ([lt]30 msec) field potentials. Single units were isolated offline by filtering, threshold detection and cluster cutting. Units were grouped based on mean firing rate, spikewidth and inter-spike interval distribution as [quot]bursting[quot] (putative granule cells; N=35 epi, 15 ctrl), [quot]tonically active[quot] (putative interneurons; N=19 epi, 8 ctrl) or [quot]unclassed[quot] (did not fit criteria above; N=11 epi, 10 ctrl), which were not analyzed. DES occurred five times more frequently in epileptic rats during inter-ictal baseline (4-8 minutes prior to seizure onset) than in controls (0.16[plusmn]0.13 Hz ctrl; 0.89[plusmn]0.04 Hz epi), and DES amplitude tended to be larger in epileptics than in controls. In epileptic rats, the frequency of DES began to decrease steadily [sim]3 minutes prior to seizure onset, reaching 61[plusmn]9 % of the baseline frequency. Although DES frequency decreased, amplitude tended to increase. Near onset in 9 of 13 seizures, large, single DES were observed with amplitudes at least twice the baseline level. To evaluate the efficacy of DES in activating neurons, we analyzed unit firing rates during DES. Interneuron firing rates during DES were similar in controls and in epileptic rats during both the inter-ictal baseline period and near seizure onset. Granule cell firing rates during DES, however, were significantly higher (142[plusmn]29 %, ANOVA p[lt].05) during the minute before seizure onset than in the inter-ictal baseline period or in control rats. The frequency of DES decreases prior to seizure onset, suggesting DES may be anti-convulsant and their reduction may allow seizures to develop. However, DES amplitude and the response of granule cells to DES increase near seizure onset, suggesting DES may trigger seizures. While the role of DES in the generation of spontaneous seizures remains unclear, changes in DES and unit responses in dentate gyrus clearly precede even the earliest indications of seizure onset. (Supported by NIH NS07280.)