Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States.
Elife. 2019 Aug 14;8:e48311. doi: 10.7554/eLife.48311.
Recent studies showed activation of the GABAergic neurons in the central nucleus of the amygdala (CeA) triggered cataplexy of sleep disorder narcolepsy. However, there is still no direct evidence on CeA GABAergic neurons' real-time dynamic during cataplexy. We used a deep brain calcium imaging tool to image the intrinsic calcium transient as a marker of neuronal activity changes in the narcoleptic VGAT-Cre mice by expressing the calcium sensor GCaMP6 into genetically defined CeA GABAergic neurons. Two distinct GABAergic neuronal groups involved in cataplexy were identified: spontaneous cataplexy-ON and predator odor-induced cataplexy-ON neurons. Majority in the latter group were inactive during regular sleep/wake cycles but were specifically activated by predator odor and continued their intense activities into succeeding cataplexy bouts. Furthermore, we found that CeA GABAergic neurons became highly synchronized during predator odor-induced cataplexy. We suggest that the abnormal activation and synchronization of CeA GABAergic neurons may trigger emotion-induced cataplexy.
最近的研究表明,激活杏仁中央核(CeA)中的 GABA 能神经元会引发睡眠障碍性发作性睡病的猝倒。然而,目前仍没有关于 CeA GABA 能神经元在猝倒时实时动态的直接证据。我们使用深部脑钙成像工具,通过在遗传定义的 CeA GABA 能神经元中表达钙传感器 GCaMP6,以神经元活动变化的内在钙瞬变为标记,对发作性睡病 VGAT-Cre 小鼠进行成像。鉴定出两种参与猝倒的不同 GABA 能神经元群:自发性猝倒 ON 神经元和捕食者气味诱导的猝倒 ON 神经元。后者中的大多数在正常的睡眠/觉醒周期中不活跃,但会被捕食者气味特异性激活,并在随后的猝倒发作中持续强烈活动。此外,我们发现 CeA GABA 能神经元在捕食者气味诱导的猝倒中高度同步化。我们认为,CeA GABA 能神经元的异常激活和同步可能引发情绪诱导的猝倒。