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- Title
Discrete subicular circuits control generalization of hippocampal seizures.
- Authors
Fei, Fan; Wang, Xia; Xu, Cenglin; Shi, Jiaying; Gong, Yiwei; Cheng, Heming; Lai, Nanxi; Ruan, Yeping; Ding, Yao; Wang, Shuang; Chen, Zhong; Wang, Yi
- Abstract
Epilepsy is considered a circuit-level dysfunction associated with imbalanced excitation-inhibition, it is therapeutically necessary to identify key brain regions and related circuits in epilepsy. The subiculum is an essential participant in epileptic seizures, but the circuit mechanism underlying its role remains largely elusive. Here we deconstruct the diversity of subicular circuits in a mouse model of epilepsy. We find that excitatory subicular pyramidal neurons heterogeneously control the generalization of hippocampal seizures by projecting to different downstream regions. Notably, anterior thalamus-projecting subicular neurons bidirectionally mediate seizures, while entorhinal cortex-projecting subicular neurons act oppositely in seizure modulation. These two subpopulations are structurally and functionally dissociable. An intrinsically enhanced hyperpolarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission, thus contributing to the generalization of hippocampal seizures. These results demonstrate that subicular circuits have diverse roles in epilepsy, suggesting the necessity to precisely target specific subicular circuits for effective treatment of epilepsy. The subiculum is known to contribute to seizures in epilepsy. Here the authors investigate the circuit mechanism by which the subiculum contributes to initiation and propagation of hippocampal seizures in a mouse model.
- Subjects
PYRAMIDAL neurons; SEIZURES (Medicine); ENTORHINAL cortex; HIPPOCAMPUS (Brain); EPILEPSY; GENERALIZATION
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-32742-x