Abstract

In the mouse, Period-2 (Per2) expression in tissues peripheral to the suprachiasmatic nuclei (SCN) increases during sleep deprivation and at times of the day when animals are predominantly awake spontaneously, suggesting that the circadian sleep-wake distribution directly contributes to the daily rhythms in Per2. We found support for this hypothesis by recording sleep-wake state alongside PER2 bioluminescence in freely behaving mice, demonstrating that PER2 bioluminescence increases during spontaneous waking and decreases during sleep. The temporary reinstatement of PER2-bioluminescence rhythmicity in behaviorally arrhythmic SCN-lesioned mice submitted to daily recurring sleep deprivations substantiates our hypothesis. Mathematical modelling revealed that PER2 dynamics can be described by a damped harmonic oscillator driven by two forces: a sleep-wake-dependent force and a SCN-independent circadian force. Our work underscores the notion that in peripheral tissues the clock gene circuitry integrates sleep-wake information and could thereby contribute to behavioral adaptability to respond to homeostatic requirements.

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Data underlying the experimental figures is available through the source files.

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Author details

  1. Marieke MB Hoekstra

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0723-2026
  2. Maxime Jan

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Georgia Katsioudi

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Yann Emmenegger

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul Franken

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    For correspondence
    paul.franken@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2500-2921

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (146694)

  • Marieke MB Hoekstra

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (179190)

  • Georgia Katsioudi

State of Vaud

  • Marieke MB Hoekstra
  • Maxime Jan
  • Yann Emmenegger
  • Paul Franken

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

Ethics

Animal experimentation: All experiments were approved by the Ethical Committee of the State of VaudVeterinary Office Switzerland under license VD 2743, 3201 and 3402.

Copyright

© 2021, Hoekstra 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. Marieke MB Hoekstra
  2. Maxime Jan
  3. Georgia Katsioudi
  4. Yann Emmenegger
  5. Paul Franken
(2021)
The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2
eLife 10:e69773.
https://doi.org/10.7554/eLife.69773

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https://doi.org/10.7554/eLife.69773