Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.
Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.
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DOI：
10.1073/pnas.2301951120
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发表时间：
2023-10-10
影响因子：
11.1
通讯作者：
Yamanaka, Akihiro
中科院分区：
文献类型：
--
作者：
Ito, Hiroto;Fukatsu, Noriaki;Rahaman, Sheikh Mizanur;Mukai, Yasutaka;Izawa, Shuntaro;Ono, Daisuke;Kilduff, Thomas S.;Yamanaka, Akihiro
发作性睡病是由食欲素神经元变性引起的食欲素信号传导不足引起的睡眠障碍。然而，潜在的神经机制快速眼动（REM）睡眠相关的发作性睡病的神经病学仍然不清楚。我们确定了以前不确定的细节食欲素神经元的活动动力学在NREM睡眠，REM睡眠，cataerosis在人口水平的纤维光度法和显微内窥镜在单神经元水平。使用光遗传学方法，我们发现NREM睡眠期间的食欲素神经元活动调节NREM-REM睡眠转换，而REM睡眠期间的食欲素神经元活动调节REM睡眠结构和cataemia。总的来说，这项研究促进了对食欲素神经元如何正常调节REM睡眠结构的理解，以及这种调节的丧失如何有助于嗜睡症的REM睡眠相关的神经病学。嗜睡症是一种由食欲素信号缺乏引起的睡眠障碍。然而，缺乏食欲素信号传导导致发作性睡病的异常快速眼动（REM）睡眠特征，如cataerosis和频繁过渡到REM状态的神经机制尚未完全了解。在这里，我们确定了食欲素神经元在睡眠过程中的活动动力学，抑制发作性睡病的异常REM睡眠结构。食欲素神经元在清醒期间高度活跃，在非REM（NREM）睡眠期间表现出间歇性同步活动，在从NREM到REM睡眠的过渡之前是静止的，并且这些细胞的一小部分亚群在REM睡眠期间活跃。缺乏食欲素肽的食欲素神经元在REM睡眠期间不太活跃，并且在cataelation期间大多是沉默的。食欲素神经元的光发生抑制证实了这些细胞在NREM睡眠期间的活动动力学调节NREM-REM睡眠转换。在REM睡眠期间抑制食欲素神经元增加了“食欲素完整”小鼠随后的REM睡眠和缺乏食欲素肽的小鼠随后的紧张症，表明在前一个REM睡眠期间食欲素神经元亚群的活性抑制了随后的REM睡眠和紧张症。因此，这些结果确定了睡眠期间食欲素信号的缺乏如何导致发作性睡病的异常REM睡眠结构特征。
Narcolepsy is a sleep disorder caused by deficient orexin signaling due to orexin neuron degeneration. However, the neural mechanisms underlying the rapid eye movement (REM) sleep-related symptomatology of narcolepsy remain unclear. We determined previously uncertain details of orexin neuron activity dynamics during NREM sleep, REM sleep, and cataplexy at the population-level by fiber photometry and at the single-neuron level by microendoscopy. Using optogenetic approaches, we found that orexin neuron activity during NREM sleep regulates NREM–REM sleep transitions whereas orexin neuron activity during REM sleep regulates REM sleep structure and cataplexy. Collectively, this study advances understanding of how orexin neurons normally regulate REM sleep architecture, and how loss of this regulation contributes to the REM sleep–related symptomatology of narcolepsy. Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM–REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in “orexin intact” mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.
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影响因子：
4.7
作者：
Barnes AK;Koul-Tiwari R;Garner JM;Geist PA;Datta S
通讯作者：
Datta S
影响因子：
4.6
作者：
Inutsuka A;Yamashita A;Chowdhury S;Nakai J;Ohkura M;Taguchi T;Yamanaka A
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影响因子：
64.5
作者：
Lin, L;Faraco, J;Mignot, E
通讯作者：
Mignot, E
影响因子：
5.6
作者：
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通讯作者：
Peyron, Christelle
影响因子：
5.3
作者：
Lee, MG;Hassani, OK;Jones, BE
通讯作者：
Jones, BE