The Circadian Control of Sleep

Abstract

The sleep/wake cycle is arguably the most familiar output of the circadian system, however, sleep is a complex biological process that arises from multiple brain regions and neurotransmitters, which is regulated by numerous physiological and environmental factors. These include a circadian drive for wakefulness as well as an increase in the requirement for sleep with prolonged waking (the sleep homeostat). In this chapter, we describe the regulation of sleep, with a particular emphasis on the contribution of the circadian system. Since their identification, the role of clock genes in the regulation of sleep has attracted considerable interest, and here, we provide an overview of the interplay between specific elements of the molecular clock with the sleep regulatory system. Finally, we summarise the role of the light environment, melatonin and social cues in the modulation of sleep, with a focus on the role of melanopsin ganglion cells.

Melatonin Is Required for the Circadian Regulation of Sleep

“…Several lines of evidence suggest that accumulation of extracellular adenosine in specific brain regions plays an important role in the homeostatic mechanism, although it is clear that other factors are also required (reviewed in Brown et al, 2012). However, while mechanisms that regulate the circadian clock are well-characterized (Fisher et al, 2013), molecules that transmit circadian information to regulate sleep are largely unknown.…”

“…Melatonin is an attractive candidate for mediating the circadian process because the clock regulates its production (Klein, 2007) and it induces sleep in some contexts (Fisher et al, 2013). However, despite decades of study and widespread use, the role of melatonin in regulating sleep is controversial (Fisher et al, 2013).…”

“…However, despite decades of study and widespread use, the role of melatonin in regulating sleep is controversial (Fisher et al, 2013). Exogenous melatonin is reported to have sleep-promoting effects in diurnal vertebrates including humans (Brzezinski et al, 2005; Zhdanova, 2005), nonhuman primates (Zhdanova et al, 2002), domesticated cats (Goldstein and Pavel, 1981), birds (Mintz et al, 1998) and zebrafish (Zhdanova et al, 2001).…”

Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy

“…We assessed this intrinsic activity of ipRGCs from the post-stimulus pupil size following monocular as well as binocular light stimulation in patients with unilateral and bilateral AION. Finally, we surveyed the sleep habit of these patients via standardized questionnaires272829 to understand how AION in one or both eyes might influence downstream physiologic processes such as sleep homeostasis which is strongly linked to melanopsin-based light signaling30.…”

Neurobiological Role of Hypocretin in Regulation of Psychiatric Disorders

“…The waking state is controlled by several neurobiological networks, including circadian, homeostatic influences as well as by genetic, molecular, neuroanatomical and neurochemical elements [12][13][14]. For example, waking is modulated by the activity of diverse neurotransmitter systems such as noradrenaline, dopamine, serotonin, acetylcholine, histamine and hypocretin [3,[15][16][17][18][19][20][21][22][23][24] (Fig.…”