International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; PhD Program in Kansei, Behavioral, and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8574, Japan.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Curr Biol. 2020 Mar 23;30(6):1002-1010.e4. doi: 10.1016/j.cub.2020.01.047. Epub 2020 Feb 6.
Classical transection studies suggest that, in addition to the hypothalamus, the brainstem is essential for non-rapid eye movement (NREM) sleep. The circuits underlying this function, however, have remained largely unknown. We identified a circuit distributed in the midbrain, pons, and medulla that promotes NREM sleep in mice. We focused on the sublaterodorsal tegmentum, an area implicated in dual regulation of REM and NREM sleep. Transcriptomic and genetic analyses revealed that neurons positive for the neuropeptide neurotensin promote NREM sleep. Further analyses identified downstream NREM sleep-promoting neurons in the dorsal deep mesencephalic nucleus, the lateral part of the periaqueductal gray, and the medial vestibular nucleus that were also neurotensinergic. Infusion of neurotensin into the fourth ventricle induced NREM sleep-like cortical activity, whereas mice deficient for neurotensin exhibited increased REM sleep, implicating the involvement of the neuropeptide itself. These findings identify a widely distributed NREM sleep-regulating circuit in the brainstem with a common molecular property.
经典的横断研究表明，除了下丘脑，脑干对于非快速眼动（NREM）睡眠也是必不可少的。然而，这一功能的相关回路在很大程度上仍然未知。我们在小鼠中鉴定出一个分布于中脑、脑桥和延髓的促进 NREM 睡眠的回路。我们专注于涉及 REM 和 NREM 睡眠双重调节的亚外侧背侧被盖区。转录组学和遗传分析表明，神经降压素阳性神经元促进 NREM 睡眠。进一步的分析确定了位于背侧深部脑桥核、导水管周围灰质外侧部分和内侧前庭核中的下游 NREM 睡眠促进神经元也是神经降压素能的。神经降压素注入第四脑室可诱导类似于 NREM 睡眠的皮质活动，而神经降压素缺乏的小鼠则表现出 REM 睡眠增加，表明该神经肽本身的参与。这些发现确定了一个具有共同分子特性的广泛分布于脑干的 NREM 睡眠调节回路。
