A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy
A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy
复制标题
去抑制性黑质束旁通路放大颞叶癫痫发作
DOI：
10.1038/s41467-020-14648-8
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发表时间：
2020-02-17
影响因子：
16.6
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
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作者：
Chen, Bin;Xu, Cenglin;Chen, Zhong
黑质网状部 (SNr) 参与颞叶癫痫 (TLE) 的精确回路仍不清楚。在这里，我们发现SNr小清蛋白(+) (PV) GABA能神经元的光遗传学或化学遗传学激活会放大引火和红藻氨酸诱导的TLE模型中的癫痫发作活动，而选择性抑制这些神经元会减轻癫痫发作活动。癫痫发作的严重程度通过投射到束旁核（PF）的 SNr PV 纤维的光遗传学操作进行双向调节。电生理学与狂犬病病毒辅助电路映射相结合表明，SNr PV 神经元直接投射到后 PF GABA 能神经元，并在功能上抑制后部 PF GABA 能神经元。这些神经元的活动也调节癫痫发作活动。总的来说，我们的结果表明，长程 SNr-PF 去抑制回路参与调节 TLE 的癫痫发作，并且该回路的失活可以减轻癫痫发作的严重程度。这些发现从回路角度更好地理解了病理变化，并提出了精确控制癫痫的可能性。
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.