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

被引：92

作者：

Chen, Bin ^{[1
]}

Xu, Cenglin ^{[1
]}

Wang, Yi ^{[1
,2
]}

Lin, Wenkai ^{[1
]}

Wang, Ying ^{[1
]}

Chen, Liying ^{[1
]}

Cheng, Heming ^{[1
]}

Xu, Lingyu ^{[1
]}

Hu, Tingting ^{[1
]}

Zhao, Junli ^{[1
]}

Dong, Ping ^{[1
]}

Guo, Yi ^{[2
]}

Zhang, Shihong ^{[1
]}

Wang, Shuang ^{[2
]}

Zhou, Yudong ^{[1
]}

Hu, Weiwei ^{[1
]}

Duan, Shuming ^{[1
]}

Chen, Zhong ^{[1
,2
,3
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Sch Basic Med Sci, Key Lab Med Neurobiol,Minist Hlth China,Dept Phar, Hangzhou, Peoples R China

[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Epilepsy Ctr,Dept Neurol, Hangzhou, Peoples R China

[3] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SUBSTANTIA-NIGRA; BASAL GANGLIA; PARS RETICULATA; THALAMIC NUCLEI; ELECTRICAL-STIMULATION; KINDLING MODEL; MOUSE MODEL; ANTICONVULSANT; NEURONS; INVOLVEMENT;

D O I：

10.1038/s41467-020-14648-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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