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

Author

Listed:
  • Bin Chen

    (Zhejiang University)

  • Cenglin Xu

    (Zhejiang University)

  • Yi Wang

    (Zhejiang University
    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
    Zhejiang University
    Zhejiang Chinese Medical University)

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.

Suggested Citation

  • 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 H, 2020. "A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14648-8
    DOI: 10.1038/s41467-020-14648-8
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    Cited by:

    1. Yunhu Bai & Kenan Li & Xiaodong Li & Xiyu Chen & Jie Zheng & Feifei Wu & Jinghao Chen & Ze Li & Shuai Zhang & Kun Wu & Yong Chen & Yayun Wang & Yanling Yang, 2023. "Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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