TY - JOUR
T1 - Gating and the need for sleep
T2 - Dissociable effects of adenosine a1and a2areceptors
AU - Lazarus, Michael
AU - Oishi, Yo
AU - Bjorness, Theresa E.
AU - Greene, Robert W.
N1 - Publisher Copyright:
© 2007 - 2019 Frontiers Media S.A.
PY - 2019
Y1 - 2019
N2 - 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 A1 or A2A receptors (A1Rs or A2ARs). Many cells and processes appear to play a role in modulating the extracellular concentration of adenosine at neuronal A1R or A2AR sites. Emerging evidence suggests that A1Rs and A2ARs have different roles in the regulation of sleep. In this review, we propose a model in which A2ARs allow the brain to sleep, i.e., these receptors provide sleep gating, whereas A1Rs 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.
AB - 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 A1 or A2A receptors (A1Rs or A2ARs). Many cells and processes appear to play a role in modulating the extracellular concentration of adenosine at neuronal A1R or A2AR sites. Emerging evidence suggests that A1Rs and A2ARs have different roles in the regulation of sleep. In this review, we propose a model in which A2ARs allow the brain to sleep, i.e., these receptors provide sleep gating, whereas A1Rs 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.
KW - A1 receptor
KW - A2A receptor
KW - Adenosine
KW - Dopamine
KW - Motivation
KW - Sleep homeostasis
KW - Slow-wave activity
KW - Slow-wave sleep
UR - http://www.scopus.com/inward/record.url?scp=85073883859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073883859&partnerID=8YFLogxK
U2 - 10.3389/fnins.2019.00740
DO - 10.3389/fnins.2019.00740
M3 - Review article
C2 - 28646346
AN - SCOPUS:85073883859
SN - 1662-4548
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - JUL
M1 - 740
ER -