Liu Kai, Kim Juhyun, Kim Dong Won, Zhang Yi Stephanie, Bao Hechen, Denaxa Myrto, Lim Szu-Aun, Kim Eileen, Liu Chang, Wickersham Ian R, Pachnis Vassilis, Hattar Samer, Song Juan, Brown Solange P, Blackshaw Seth
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Nature. 2017 Aug 31;548(7669):582-587. doi: 10.1038/nature23663. Epub 2017 Aug 23.
Multiple populations of wake-promoting neurons have been characterized in mammals, but few sleep-promoting neurons have been identified. Wake-promoting cell types include hypocretin and GABA (γ-aminobutyric-acid)-releasing neurons of the lateral hypothalamus, which promote the transition to wakefulness from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Here we show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus and receive inputs from multiple sleep-wake-regulating neurons. Conditional deletion of Lhx6 from the developing diencephalon leads to decreases in both NREM and REM sleep. Furthermore, selective activation and inhibition of Lhx6-positive neurons in the ventral zona incerta bidirectionally regulate sleep time in adult mice, in part through hypocretin-dependent mechanisms. These studies identify a GABAergic subpopulation of neurons in the ventral zona incerta that promote sleep.
在哺乳动物中，已对多种促进清醒的神经元群体进行了表征，但已鉴定出的促进睡眠的神经元却很少。促进清醒的细胞类型包括下丘脑外侧分泌食欲素和γ-氨基丁酸（GABA）的神经元，它们促进从非快速眼动（NREM）睡眠和快速眼动（REM）睡眠向清醒状态的转变。我们在此表明，小鼠腹侧未定带中的一部分GABA能神经元，表达LIM同源域因子Lhx6并被睡眠压力激活，它们既直接抑制下丘脑外侧的清醒活跃的食欲素和GABA能细胞，又接收来自多个睡眠-觉醒调节神经元的输入。在发育中的间脑中条件性删除Lhx6会导致NREM睡眠和REM睡眠均减少。此外，选择性激活和抑制腹侧未定带中的Lhx6阳性神经元可双向调节成年小鼠的睡眠时间，部分是通过依赖食欲素的机制。这些研究确定了腹侧未定带中促进睡眠的GABA能神经元亚群。
