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Diverse roles of pontine NPS-expressing neurons in sleep regulation.


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.

SUBMITTER: Xing L 

PROVIDER: S-EPMC10907243 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Diverse roles of pontine NPS-expressing neurons in sleep regulation.

Xing Lijuan L   Zou Xianlin X   Yin Chen C   Webb John M JM   Shi Guangsen G   Ptáček Louis J LJ   Fu Ying-Hui YH  

Proceedings of the National Academy of Sciences of the United States of America 20240221 9


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<sup>+</sup> nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS<sup>+</sup> neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS<sup>+</sup> neurons are not important for sleep/wake  ...[more]

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