Sleep timing and the circadian clock in mammals: Past, present and the road ahead

Abstract

Nearly all mammals display robust daily rhythms of physiology and behavior. These approximately 24-h cycles, known as circadian rhythms, are driven by a master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and affect biological processes ranging from metabolism to immune function. Perhaps the most overt output of the circadian clock is the sleep-wake cycle, the integrity of which is critical for health and homeostasis of the organism. In this review, we summarize our current understanding of the circadian regulation of sleep. We discuss the neural circuitry and molecular mechanisms underlying daily sleep timing, and the trajectory of circadian regulation of sleep across development. We conclude by proposing future research priorities for the field that will significantly advance our mechanistic understanding of the circadian regulation of sleep.

Keywords: Circadian rhythms; Clock genes; Sleep; Suprachiasmatic nucleus.

Fig. 1.

Simplified diagram of connections between the master circadian clock and sleep-wake circuitry. Diagram is color-coded as follows: Red = SCN, Green = generally wake-promoting, Purple = generally sleep promoting, orange = both, blue = neutral/other role, dotted lines = sparse projections. Abbreviations: ipRGCs, intrinsically photosensitive retinal ganglion cells; RHT, retinohypothalamic tract; SCN, suprachiasmatic nucleus; ARC, arcuate nucleus of the hypothalamus; VLPO, ventrolateral preoptic nucleus; dSPZ, dorsal subparaventricular zone; vSPZ, ventral subparaventricular zone; DMH, dorsomedial hypothalamus; TMN, tuberomammillary nucleus; LH, lateral hypothalamus; PVN, paraventricular nucleus; IGL, intergeniculate leaflet; PAG, periaqueductal gray; LC, locus coeruleus; SCG; spinal cervical ganglion.