A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy.
A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy.
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DOI：
10.1038/s41421-022-00456-5
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发表时间：
2022-10-25
期刊：
影响因子：
33.5
通讯作者：
Huang, Zhi-Li
中科院分区：
文献类型：
--
作者：
Chen, Ze-Ka;Dong, Hui;Liu, Cheng-Wei;Liu, Wen-Ying;Zhao, Ya-Nan;Xu, Wei;Sun, Xiao;Xiong, Yan-Yu;Liu, Yuan-Yuan;Yuan, Xiang-Shan;Wang, Bing;Lazarus, Michael;Cherasse, Yoan;Li, Ya-Dong;Han, Fang;Qu, Wei-Min;Ding, Feng-Fei;Huang, Zhi-Li
生理性快速眼动(REM)睡眠终止对于启动非快速眼动(NREM)睡眠或唤醒至关重要，而抑制过度的REM睡眠在治疗发作性睡病方面是有希望的。然而，控制REM睡眠终止和维持睡眠持续的神经机制在很大程度上仍不清楚。在这里，我们揭示了GABA能神经元在控制生理性REM睡眠和猝倒方面的一个关键脑干区域。用纤维光度法和光学四极管记录技术，研究了中脑深核(DDpMe)GABA能神经元在自发睡眠-觉醒周期中表现为REM相对不活跃和两种不同的放电模式。接下来，我们利用光遗传学、RNA干扰技术和细胞类型特异性损伤研究了dDpMe GABA能神经元电路在脑状态调节中的作用。生理上，dDpMe GABA能神经元通过背外侧核和下丘脑外侧核抑制REM睡眠，促进NREM睡眠。对神经回路的深入研究表明，背外侧核谷氨酸能神经元是dDpMe GABA能神经元终止REM睡眠所必需的。此外，dDpMe GABA能神经元有效地抑制了啮齿动物模型的猝倒。我们的结果表明，dDpMe GABA能神经元控制着REM睡眠终止以及REM/NREM转换，是治疗发作性睡病的一个新的潜在靶点。
Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep–wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy.
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影响因子：
2.2
作者：
BIXLER, EO;KALES, A;MANFREDI, RL
通讯作者：
MANFREDI, RL
影响因子：
9.2
作者：
Dong, Hui;Chen, Ze-Ka;Huang, Zhi-Li
通讯作者：
Huang, Zhi-Li
影响因子：
64.5
作者：
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通讯作者：
Yanagisawa, M
影响因子：
5.3
作者：
Boucetta, Soufiane;Cisse, Youssouf;Jones, Barbara E.
通讯作者：
Jones, Barbara E.
影响因子：
56.9
作者：
Hayashi, Yu;Kashiwagi, Mitsuaki;Itohara, Shigeyoshi
通讯作者：
Itohara, Shigeyoshi