Abstract:
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
摘要:
神经肽S(NPS)被认为是一种机制未知的促唤醒神经肽,其受体(NPSR1)的突变导致人类睡眠持续时间短。我们研究了不同NPS核在睡眠/觉醒调节中的作用。功能丧失和化学遗传学研究表明,臂旁核(PB)中的NPS神经元具有促进觉醒的作用,而周围基因座蓝斑(周围LC)NPS神经元对于睡眠/唤醒调节并不重要。Further,我们发现脑桥中央灰核(CGPn)强烈促进睡眠。纤维光度记录显示,NPS神经元在CGPn中具有唤醒活性,而在PB和周围LC中具有唤醒/REM睡眠活性。阻断NPS-NPSR1信号传导或Nps敲低支持NPS-NPSR1通路在睡眠/觉醒调节中的功能。一起,这些结果表明,NPS和NPS+神经元在分子水平和回路水平上在睡眠/觉醒调节中起着二分法的作用。