Abstract

Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control.

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The following previously published data sets were used

Article and author information

Author details

  1. Daniel A Lee

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7411-2740
  2. Andrey Andreev

    Department of Bioengineering, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thai V Truong

    Translational Imaging Center, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Audrey Chen

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew J Hill

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Grigorios Oikonomou

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Uyen Pham

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Young K Hong

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Steven Tran

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Laura Glass

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Viveca Sapin

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Jae Engle

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Scott E Fraser

    Department of Bioengineering, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. David A Prober

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    dprober@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7371-4675

Funding

National Institutes of Health (F32NS084769)

  • Daniel A Lee

National Institutes of Health (NS070911)

  • David A Prober

National Institutes of Health (DA031367)

  • David A Prober

Brain and Behavior Research Foundation (25392)

  • Daniel A Lee

Gordon and Betty Moore Foundation

  • Scott E Fraser

Edward Mallinckrodt, JR Foundation

  • David A Prober

Rita Allen Foundation

  • David A Prober

Brain and Behavior Research Foundation

  • David A Prober

National Institutes of Health (K99NS097683)

  • Daniel A Lee

National Institutes of Health (F32NS082010)

  • Grigorios Oikonomou

National Institutes of Health (MH107238)

  • Scott E Fraser

National Institutes of Health (NS060996)

  • David A Prober

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yang Dan, University of California, Berkeley, United States

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 and University of Southern California Institutional Animal Care and Use Committee guidelines.

Version history

  1. Received: February 3, 2017
  2. Accepted: November 3, 2017
  3. Accepted Manuscript published: November 6, 2017 (version 1)
  4. Version of Record published: November 28, 2017 (version 2)

Copyright

© 2017, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Daniel A Lee
  2. Andrey Andreev
  3. Thai V Truong
  4. Audrey Chen
  5. Andrew J Hill
  6. Grigorios Oikonomou
  7. Uyen Pham
  8. Young K Hong
  9. Steven Tran
  10. Laura Glass
  11. Viveca Sapin
  12. Jae Engle
  13. Scott E Fraser
  14. David A Prober
(2017)
Genetic and neuronal regulation of sleep by neuropeptide VF
eLife 6:e25727.
https://doi.org/10.7554/eLife.25727

Share this article

https://doi.org/10.7554/eLife.25727

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