Circadian Regulation of Sleep: From Genes to Circuits

The circadian clock is a genetically controlled transcriptional timing system that drives approximately 24-h rhythms in gene expression and consequently in physiology and behavior. At the molecular level, the circadian clock consists of a cell-autonomous transcription-translation feedback loop that maintains a 24-h cycle of gene expression. A master clock in the brain serves as a pacemaker for molecular clocks throughout the body to coordinate circadian rhythms with respect to one another and the external environment. Sleep is a circadian behavior, though sleep is coordinately regulated by both circadian and homeostatic processes. The interplay between brain clocks, clock output signals such as core body temperature and melatonin signaling, and sleep regulation are complex, and while research reveals some mechanistic underpinnings, other aspects require further research. Additional environmental factors regulating the clock and consequently sleep, include aging, circadian desynchrony, and immune activation. Finally, the circadian nature of so many physiological properties offers unique opportunities for chronotherapy for sleep and circadian disorders.