Differential circadian time modulates of dentate gyrus and CA1 excitation-inhibition balance and seizure threshold.
9 affiliations
- 1Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
- 2Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu, Anhui, China.
- 3Anhui Engineering Research Center for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University, Bengbu, Anhui, China.
- 4School of Basic Medicine, Bengbu Medical University, No. 287, Changhuai Road, Bengbu, Anhui, China.
- 5Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 4, Section 2, North Jianshe Road, Chengdu, Sichuan, China.
- 6Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 4, Section 2, North Jianshe Road, Chengdu, Sichuan, China. [email protected].
- 7Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China. [email protected].
- 8Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu, Anhui, China. [email protected].
- 9Anhui Engineering Research Center for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University, Bengbu, Anhui, China. [email protected].
Abstract
Circadian rhythms regulate seizure threshold and neuronal excitability in epilepsy. Temporal lobe seizures tend to arise more frequently during the diurnal phase relative to the nocturnal phase, yet dentate gyrus (DG) granule cells display elevated intrinsic excitability and CA1 pyramidal neurons show enhanced synaptic excitability at night. Here, we used male adult ICR mice (8-10 weeks old) as experimental subjects. Systemic pilocarpine injection was applied to pharmacologically trigger acute seizures, while AAV (pAAV2/9-CaMKIIα-hChR2 (H134R) - EYFP) delivery followed by optogenetic stimulation (10 Hz, 20 ms pulse width, 5 mW 473 nm blue light) was implemented to evoke region-specific hippocampal seizures. Combining continuous video-electroencephalography (vEEG) recording, optogenetically induced seizure assays, mRNA sequencing, and whole-cell patch-clamp electrophysiology, we investigated circadian modulation of neuronal excitability and seizure threshold within the DG and CA1 subfields of the hippocampus. Our results revealed divergent circadian regulation of seizure thresholds between the DG and CA1 regions. Notably, the diurnal-nocturnal seizure threshold pattern in CA1 recapitulated that seen in systemic pilocarpien-provoked seizure models. We further confirmed that circadian cycles exert distinct regulatory effects on excitatory/inhibitory synaptic transmission and the intrinsic excitability of hippocampal principal neurons in the DG and CA1. Collectively, this work highlights region-specific circadian control over seizure susceptibility and the brain excitation-inhibition balance. Elucidating circadian influences on hippocampal physiology and seizure threshold will improve the translational value of anti-epileptic therapies and guide time-stratified seizure intervention strategies.
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BibTeX
@article{ge2026differential,
title = {{Differential circadian time modulates of dentate gyrus and CA1 excitation-inhibition balance and seizure threshold.}},
author = {Rongjing Ge and Menghan Zhang and Daoming Cheng and Bingjing Sun and Hong Ni and Hui Zhang and Jianhong Liu and Hao Qian and Bei Liu and Jiandong Yu},
journal = {Molecular brain},
year = {2026},
month = aug,
doi = {10.1186/s13041-026-01346-7},
url = {https://europepmc.org/article/MED/42963541},
note = {CC BY},
}
RIS
TY - JOUR
TI - Differential circadian time modulates of dentate gyrus and CA1 excitation-inhibition balance and seizure threshold.
AU - Rongjing Ge
AU - Menghan Zhang
AU - Daoming Cheng
AU - Bingjing Sun
AU - Hong Ni
AU - Hui Zhang
AU - Jianhong Liu
AU - Hao Qian
AU - Bei Liu
AU - Jiandong Yu
PY - 2026
DA - 2026/08/28
JO - Molecular brain
DO - 10.1186/s13041-026-01346-7
UR - https://europepmc.org/article/MED/42963541
AB - Circadian rhythms regulate seizure threshold and neuronal excitability in epilepsy. Temporal lobe seizures tend to arise more frequently during the diurnal phase relative to the nocturnal phase, yet dentate gyrus (DG) granule cells display elevated intrinsic excitability and CA1 pyramidal neurons show enhanced synaptic excitability at night. Here, we used male adult ICR mice (8-10 weeks old) as experimental subjects. Systemic pilocarpine injection was applied to pharmacologically trigger acute seizures, while AAV (pAAV2/9-CaMKIIα-hChR2 (H134R) - EYFP) delivery followed by optogenetic stimulation (10 Hz, 20 ms pulse width, 5 mW 473 nm blue light) was implemented to evoke region-specific hippocampal seizures. Combining continuous video-electroencephalography (vEEG) recording, optogenetically induced seizure assays, mRNA sequencing, and whole-cell patch-clamp electrophysiology, we investigated circadian modulation of neuronal excitability and seizure threshold within the DG and CA1 subfields of the hippocampus. Our results revealed divergent circadian regulation of seizure thresholds between the DG and CA1 regions. Notably, the diurnal-nocturnal seizure threshold pattern in CA1 recapitulated that seen in systemic pilocarpien-provoked seizure models. We further confirmed that circadian cycles exert distinct regulatory effects on excitatory/inhibitory synaptic transmission and the intrinsic excitability of hippocampal principal neurons in the DG and CA1. Collectively, this work highlights region-specific circadian control over seizure susceptibility and the brain excitation-inhibition balance. Elucidating circadian influences on hippocampal physiology and seizure threshold will improve the translational value of anti-epileptic therapies and guide time-stratified seizure intervention strategies.
SN - 1756-6606
ER -