The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2

Abstract
Data availability
Article and author information
Metrics

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.

Data availability

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

Article and author information

Author details

Marieke MB Hoekstra

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0723-2026
Maxime Jan

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Georgia Katsioudi

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Yann Emmenegger

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
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.

"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

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.