A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy

Bin Chen, Cenglin Xu, Yi Wang (), Wenkai Lin, Ying Wang, Liying Chen, Heming Cheng, Lingyu Xu, Tingting Hu, Junli Zhao, Ping Dong, Yi Guo, Shihong Zhang, Shuang Wang, Yudong Zhou, Weiwei Hu, Shuming Duan and Zhong Chen ()
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Bin Chen: Zhejiang University
Cenglin Xu: Zhejiang University
Yi Wang: Zhejiang University
Wenkai Lin: Zhejiang University
Ying Wang: Zhejiang University
Liying Chen: Zhejiang University
Heming Cheng: Zhejiang University
Lingyu Xu: Zhejiang University
Tingting Hu: Zhejiang University
Junli Zhao: Zhejiang University
Ping Dong: Zhejiang University
Yi Guo: Zhejiang University
Shihong Zhang: Zhejiang University
Shuang Wang: Zhejiang University
Yudong Zhou: Zhejiang University
Weiwei Hu: Zhejiang University
Shuming Duan: Zhejiang University
Zhong Chen: Zhejiang University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy.

Date: 2020
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DOI: 10.1038/s41467-020-14648-8

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