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

View ORCID ProfileMarieke M.B. Hoekstra, View ORCID ProfileMaxime Jan, Yann Emmenegger, View ORCID ProfilePaul Franken
doi: https://doi.org/10.1101/2020.07.25.221101
Marieke M.B. Hoekstra
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
2UK Dementia Research Institute at Imperial College London, Division of Brain Sciences, London, United Kingdom
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  • ORCID record for Marieke M.B. Hoekstra
Maxime Jan
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
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Yann Emmenegger
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
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Paul Franken
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
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  • For correspondence: paul.franken@unil.ch
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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 increases during spontaneous waking and decreases during sleep. The temporary reinstatement of PER2 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.

Competing Interest Statement

The authors have declared no competing interest.

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  • ↵* share first authorship on this work

  • lay-out updated.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 03, 2021.
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The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2
Marieke M.B. Hoekstra, Maxime Jan, Yann Emmenegger, Paul Franken
bioRxiv 2020.07.25.221101; doi: https://doi.org/10.1101/2020.07.25.221101
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The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2
Marieke M.B. Hoekstra, Maxime Jan, Yann Emmenegger, Paul Franken
bioRxiv 2020.07.25.221101; doi: https://doi.org/10.1101/2020.07.25.221101

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