Abstracts

Rationale: During rapid eye movement (REM) sleep, epilepsy can be suppressed. During the period, θ rhythm is induced. So, it is thought that θ rhythm will suppress the generation of epilepsy. REM sleep includes β rhythm. But the rhythm has a suppression effect on the epilepsy has not yet been clarified. Thus, in the present study we study whether β rhythm has the effect or not using hippocampal slice model.Methods: The data were obtained from 178 hippocampal slices (450 μm thick) of 105 male Wistar rats. The recording electrode (2M NaCl, <3MΩ) was placed in stratum pyramidale in CA3 to record carbachol-induced oscillations extracellularly. Frequency is defined as a peak frequency in Fast Fourier Transform (FFT) analysis of carbachol-induced β oscillations (CIBO). Carbachol is an acetylcholine receptor agonist. FFT was applied from 2 to 3 sec for 1sec after the onset of CIBO.Results: Application of carbachol (> 30 μM) induced intermittent burst-like oscillations. Frequency in a burst was 16.6 ± 1.0 Hz (n = 5). So we call it CIBO. The application of GABAA receptor antagonists picrotoxin (PTX), bicuculline, and gabazine induced the epileptic discharges (GED). In the following, the results of PTX were shown, and the other drugs had the similar results. Thirty μM carbachol was applied to induce CIBO. Then PTX was added, but GED wasn’t induced. After carbachol was washed out, GED was induced. These results suggest that hippocampal slices can induce both CIBO and GED, but GED can be suppressed when CIBO will be induced. To study the cause of the suppression, population excitatory postsynaptic potential (pEPSP) was recorded in CA3. CA3 pyramidal neurons have recurrent network. A stimulation electrode was put in the CA3 stratum radiatum to stimulate the pyramidal cells antidromically, and to evoke pEPSP. A recording electrode was located at stratum radiatum. The stimulation was done 5 times every 1min to get a control pEPSP. Then 30 μM carbachol was applied, and pEPSP was suppressed. PEPSP slope became smaller to about 40%. After carbachol was washed out, the slope recovered to 80%. Carbachol decreased evoked EPSP significantly (n = 3; p < 0.001; one-way repeated ANOVA). GED is induced by the synchronization of CA3 pyramidal cells. The smaller EPSP the cells have, the more difficult the synchronization of the cells are. Therefore, the results suggest that carbachol decreases EPSP in the generation of CIBO and in results the epileptic discharges can be suppressed.Conclusions: An acetylcholine receptor agonist carbachol induced β oscillations. GABAA receptor antagonists induced the epileptic discharges. Despite at the concentration which induces the epileptic discharges, the discharges were not induced during β oscillation was induced. Carbachol also decreased pEPSP slope significantly. To induce the epileptic discharges, CA3 pyramidal cells need to synchronize. Therefore the decrease in EPSP in β oscillation will lead to the suppression of the epileptic discharges. In REM sleep, β rhythm can suppress epilepsy as well as θ rhythm. Funding: KAKENHI 24120712