Department of Neurology, University of California, San Francisco, CA 94143.
Weill Institute for Neurosciences, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2203266119. doi: 10.1073/pnas.2203266119. Epub 2022 Jul 28.
Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRN) that regulate sleep-wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRN neuron stimulation strongly promotes wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRN neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on multiplexed analysis of projections by sequencing (MAPseq) analysis. Finally, we found that pTRN neurons promote wakefulness, in part, through projections to the lateral hypothalamus. Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep-wake regulation.
睡眠是我们生存的必需品，但睡眠的调节机制仍不完全清楚。在这里，我们使用人类睡眠时间基因来鉴定出调节睡眠-觉醒的中脑被盖旁网状核（pTRN）中的一群细胞，揭示了一个鲜为人知的大脑区域的作用。尽管最初在小鼠中消融会导致清醒增加，但进一步的验证表明，pTRN 神经元刺激强烈促进清醒，即使在刺激结束后也是如此。使用组合遗传学，我们发现兴奋性 pTRN 神经元促进觉醒。pTRN 神经元可以根据通过测序（MAPseq）分析进行的投射的多路复用分析，被特征化为前投射或后投射神经元。最后，我们发现 pTRN 神经元通过向外侧下丘脑投射来促进觉醒。因此，来自人类睡眠特征的人类遗传信息使我们能够确定 pTRN 在睡眠-觉醒调节中的作用。
