Circadian alterations of dentate gyrus excitability may contribute to the afternoon peak of seizures in experimental mesial temporal lobe epilepsy

In human mesial temporal lobe epilepsy (mTLE), seizure occurrence peaks in the late afternoon and early evening. This temporal binding of seizures is also manifest in animal models of mTLE developing as a consequence of electrically-induced status epilepticus. In this study, we hypothesized that circadian alterations in excitatory and inhibitory functions of the dentate gyrus (DG), which is believed to regulate the generation of limbic seizures, form the pathophysiological basis for the predominant occurrence of seizures in the late afternoon/early evening. We performed electrophysiological single and paired pulse measurements hourly over 24h in the DG of chronically epileptic rats (n=7) 8 weeks after electrically induced status epilepticus. Data obtained before induction of SE served as individual controls. Pre and post data were compared in two distinct phases of the day, i.e. a high-seizure phase between 2p.m. and 10p.m. and a low-seizure phase between 10p.m. and 2p.m. In chronic epileptic animals, latency of evoked potentials was significantly reduced in the high-seizure phase (p=0.027) but not in the low-seizure phase. Paired pulse inhibition with short interpulse intervals (IPI) was significantly increased during the low-seizure phase (IPI 25ms, p=0.03; IPI 30ms, p<0.001) but not in the high-seizure phase. These data indicate increased DG excitability in the late afternoon/early evening that may contribute to the time of day-dependency of spontaneous seizures in this animal model of mTLE. Regulation of DG excitability may be influenced by diurnal alterations of hypothalamic functions such as endocrine hormones or temperature but to clariy this issue further studies are needed.