Elife.: auth.: group Franken

Elife. 2021 Dec 13;10:e69773. doi: 10.7554/eLife.69773. Online ahead of print.

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

Marieke Mb Hoekstra 1Maxime Jan 1Georgia Katsioudi 1Yann Emmenegger 1Paul Franken 1


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.

Keywords: computational biology; mouse; neuroscience; systems biology.