Journal
FRONTIERS IN NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.00740
Keywords
adenosine; slow-wave sleep; A(2A) receptor; A(1) receptor; slow-wave activity; sleep homeostasis; dopamine; motivation
Categories
Funding
- Japan Society for the Promotion of Science [17H02215]
- Japan Science and Technology Agency [CREST] [JPMJCR1655]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [15H05935, 15K21745, 18H04966, 19H05004]
- World Premier International Research Center Initiative (WPI) from MEXT
- Astellas Foundation for Research on Metabolic Disorders
- National Institutes of Health [MH 06777, NS075545]
- Department of Veterans Affairs through Dallas VA Medical Center [MH79710, MH083711]
- Grants-in-Aid for Scientific Research [19H05004, 18H04966, 17H02215] Funding Source: KAKEN
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Roughly one-third of the human lifetime is spent in sleep, yet the reason for sleep remains unclear. Understanding the physiologic function of sleep is crucial toward establishing optimal health. Several proposed concepts address different aspects of sleep physiology, including humoral and circuit-based theories of sleep-wake regulation, the homeostatic two-process model of sleep regulation, the theory of sleep as a state of adaptive inactivity, and observations that arousal state and sleep homeostasis can be dissociated in pathologic disorders. Currently, there is no model that places the regulation of arousal and sleep homeostasis in a unified conceptual framework. Adenosine is well known as a somnogenic substance that affects normal sleep-wake patterns through several mechanisms in various brain locations via A(1) or A(2A) receptors (A(1)Rs or A(2A)Rs). Many cells and processes appear to play a role in modulating the extracellular concentration of adenosine at neuronal A(1)R or A(2A)R sites. Emerging evidence suggests that A(1)Rs and A(2A)Rs have different roles in the regulation of sleep. In this review, we propose a model in which A(2A)Rs allow the brain to sleep, i.e., these receptors provide sleep gating, whereas A(1)Rs modulate the function of sleep, i.e., these receptors are essential for the expression and resolution of sleep need. In this model, sleep is considered a brain state established in the absence of arousing inputs.
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