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Xing, Lijuan; Zou, Xianlin; Yin, Chen; Webb, John M; Shi, Guangsen; Ptáček, Louis J; Fu, Ying-Hui
Proceedings of the National Academy of Sciences - PNAS, 02/2024, Letnik: 121, Številka: 9Journal Article
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 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.
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