Diverse roles of pontine NPS- expressing neurons in sleep regulation

• 成果类型: Article
• 署名作者: Xing, Lijuan; Zou, Xianlin; Yin, Chen; Webb, John M.; Shi, Guangsen; Ptacek, Louis J.; Fu, Ying- Hui
• 署名单位: University of California System; University of California San Francisco; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12137
• DOI: 10.1073/pnas.2320276121
• 发表日期: 2024-02-27
• 关键词: neuropeptide-s; rem-sleep; hypocretin orexin; neural circuitry; in-vivo; mice; antagonist; contribute; BEHAVIOR; arousal

摘要

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.