Discrete subicular circuits control generalization of hippocampal seizures

Fan Fei, Xia Wang, Cenglin Xu (), Jiaying Shi, Yiwei Gong, Heming Cheng, Nanxi Lai, Yeping Ruan, Yao Ding, Shuang Wang, Zhong Chen () and Yi Wang ()
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Fan Fei: Zhejiang University
Xia Wang: Zhejiang University
Cenglin Xu: Zhejiang Chinese Medical University
Jiaying Shi: Zhejiang University
Yiwei Gong: Zhejiang University
Heming Cheng: Zhejiang Chinese Medical University
Nanxi Lai: Zhejiang University
Yeping Ruan: Zhejiang Chinese Medical University
Yao Ding: Zhejiang University
Shuang Wang: Zhejiang University
Zhong Chen: Zhejiang University
Yi Wang: Zhejiang University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32742-x

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