Abstract
Circadian clocks drive biological rhythms with a period of approximately 24 hours and keep in time with the outside world through daily resetting by environmental cues. While this external entrainment has been extensively investigated in the suprachiasmatic nuclei (SCN), the role of internal systemic rhythms, including daily fluctuations in core temperature or circulating hormones remains debated. Here, we show that lactating mice, which exhibit dampened systemic rhythms, possess normal molecular clockwork but impaired rhythms in both heat shock response gene expression and electrophysiological output in their SCN. This suggests that body rhythms regulate SCN activity downstream of the clock. Mathematical modeling predicts that systemic feedback upon the SCN functions as an internal oscillator that accounts for in vivo and ex vivo observations. Thus we are able to propose a new bottom-up hierarchical organization of circadian timekeeping in mammals, based on the interaction in the SCN between clock-dependent and system-driven oscillators.
Highlights
The suprachiasmatic nuclei (SCN) of the hypothalamus lie at the top of the mammalian circadian system
Using a lactating mouse paradigm, we were able to disclose the dual regulation of SCN daily oscillations by the circadian clock and systemic rhythms
The impaired rhythm in system-driven gene expression in the SCN of lactating mice indicates that physiological conditions impinge upon SCN rhythmicity
Summary
The suprachiasmatic nuclei (SCN) of the hypothalamus lie at the top of the mammalian circadian system. They contain the central circadian pacemaker that regulates daily rhythms in physiology and behavior, and synchronizes subordinated circadian oscillators throughout the body [1]. Resetting by external rhythms keeps the SCN exactly in tune with the 24-hour period of the outside world. Whether internal body rhythms are able to entrain and regulate the pace of SCN oscillations is less clear. The SCN molecular clockwork is resilient to major systemic rhythms, such as daily variations in glucocorticoids and core body temperature, which is thought to prevent
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