Differential Circadian Time Modulates of Dentate Gyrus and CA1 Excitation-Inhibition Balance and Seizure Threshold.

The circadian rhythm modulates seizure threshold and neuronal excitability. Seizures in temporal lobe epilepsy are more likely to occur during the diurnal phase compared to the nocturnal phase. However, the intrinsic excitability of dentate gyrus granule cells and the state of synaptic transmission in CA1 pyramidal neurons exhibit relatively high excitability during the nocturnal phase. To investigate how circadian time modulates neuronal excitability and seizure threshold in the dentate gyrus and CA1, we utilized video-electroencephalography monitoring, systemic administration of pilocarpine, optogenetically induced seizures, mRNA sequencing, and whole-cell patch clam techniques.Our findings demonstrate that circadian time exerts differential modulation on the seizure threshold in dentate gyrus and the CA1.Furthermore, the circadian modulation of the CA1 seizure threshold is similar to that observed with systemic administration of pilocarpine-induced seizures. We also found that circadian rhythms differentially modulate excitatory and inhibitory synaptic transmission, as well as the intrinsic excitability of principal neurons in both the dentate gyrus and CA1. This study emphasizes the significance of circadian regulation in different brain regions concerning seizure threshold and the excitation-inhibition balance. Understanding how circadian rhythms influence hippocampal physiology and seizure threshold can enhance the translational relevance of therapeutics and inform the optimal timing for seizure management。