Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Pharmacology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Nat Commun. 2020 Feb 17;11(1):923. doi: 10.1038/s41467-020-14648-8.
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.
参与颞叶癫痫（TLE）的黑质网状部（SNr）精确回路仍不清楚。在这里，我们发现光遗传学或化学遗传学激活 SNr 小脑浦肯野细胞（PV）GABA 能神经元可放大点燃和海人酸诱导的 TLE 模型中的癫痫活动，而选择性抑制这些神经元可减轻癫痫活动。通过对投射到束旁核（PF）的 SNr PV 纤维进行光遗传学操纵，可双向调节癫痫发作的严重程度。电生理学结合狂犬病病毒辅助回路映射显示，SNr PV 神经元直接投射到并功能性抑制后部 PF GABA 能神经元。这些神经元的活动也调节癫痫发作。总之，我们的研究结果表明，长程 SNr-PF 去抑制回路参与调节 TLE 中的癫痫发作，而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，并提示了精确控制癫痫的可能性。
