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Neuropeptide VF neurons promote sleep via the serotonergic raphe

Lee, Daniel A. and Oikonomou, Grigorios and Cammidge, Tasha and Andreev, Andrey and Hong, Young and Hurley, Hannah and Prober, David A. (2020) Neuropeptide VF neurons promote sleep via the serotonergic raphe. eLife, 9 . Art. No. e54491. ISSN 2050-084X. PMCID PMC7748413.

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Although several sleep-regulating neuronal populations have been identified, little is known about how they interact with each other to control sleep/wake states. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we show using zebrafish that npvf-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that is critical for sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and can activate serotonergic RN neurons. We also demonstrate that chemogenetic or optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and serotonin in the RN. Finally, we provide genetic evidence that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain neuronal circuit for sleep/wake control.

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URLURL TypeDescription CentralArticle letter response Paper
Lee, Daniel A.0000-0001-7411-2740
Oikonomou, Grigorios0000-0001-6797-7375
Andreev, Andrey0000-0002-7833-1390
Hong, Young0000-0001-9548-5511
Prober, David A.0000-0002-7371-4675
Additional Information:© 2020, Lee et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 27 December 2019; Accepted: 23 November 2020; Published: 18 December 2020. We thank members of the Prober lab for helpful discussions; Sarah Hou for experimental assistance; Uyen Pham, Chris Cook, Caressa Wong, Axel Dominguez and Alex Mack for zebrafish husbandry assistance; and Andres Collazo, Giada Spigolon, and the Beckman Institute Biological Imaging Facility for 2-photon imaging assistance. This work was supported by grants from the NIH (DAL: K99NS097683, F32NS084769; GO: F32NS082010; DAP: NS070911, NS101158), a NARSAD Young Investigator Grant (DAL: 25392) and a Caltech BBE Postdoctoral Fellowship to DAL. The authors declare no competing interests. Author contributions: Daniel A Lee, Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing; Grigorios Oikonomou, Resources, Software, Methodology, Writing - review and editing; Tasha Cammidge, Young Hong, Data curation, Formal analysis, Investigation; Andrey Andreev, Resources, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology; Hannah Hurley, Formal analysis, Investigation; David A Prober, Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition, Project administration, Writing - review and editing. Ethics: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were performed using standard protocols (Westerfield, 1993) in accordance with the California Institute of Technology Institutional Animal Care and Use Committee guidelines and by the Office of Laboratory Animal Resources at the California Institute of Technology (animal protocol 1580). Data availability: All data generated or analyzed during this study are included in the manuscript and supporting files. Details described in this paper regarding transgenic and mutant animals have been deposited at ZFIN.
Funding AgencyGrant Number
NIH Postdoctoral FellowshipF32NS084769
NIH Postdoctoral FellowshipF32NS082010
Brain and Behavior Research Foundation25392
Caltech Division of Biology and Biological EngineeringUNSPECIFIED
PubMed Central ID:PMC7748413
Record Number:CaltechAUTHORS:20200102-084029093
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Official Citation:Neuropeptide VF neurons promote sleep via the serotonergic raphe. Lee et al. eLife 2020;9: e54491. DOI:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100443
Deposited By: Tony Diaz
Deposited On:02 Jan 2020 19:43
Last Modified:22 Dec 2020 17:33

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