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. 2019 Apr 24;13:336. doi: 10.3389/fnins.2019.00336

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Copyright © 2019 Harding, Franks and Wisden.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Sensory and homeostatic inputs that gate sleep. Sleep onset is determined by four competing inputs: the homeostatic drive to sleep and three permissive conditions that relate to sleep timing, the behavioural input, the circadian input and the autonomic input. Endocrine inputs are also a key part of each category. Ghrelin and leptin are important for sensing of hunger/satiety, respectively, while melatonin is a key component of the circadian rhythm. Adenosine and NO may form part of the homeostatic input. (Top - Factors promoting wakefulness) Circadian cues are permissive for wake and homeostatic pressure to sleep is low. Behavioural factors also promote wakefulness and autonomic inputs are not permissive for sleep. Wake promoting nuclei drive cortical and thalamic excitability, whilst inhibiting sleep-prompting areas such as PO and vPAG. Behavioural needs of food and reproduction overcome those of sleep and thermal comfort. Behavioural inputs are also wake-promoting and may integrate this information in the VTA. Hormonal inputs, such as ghrelin, are detected in the ARC and are sleep-permissive. Autonomic signals, such as ambient temperature, are relayed via the spinal cord and pass through the LPb to the PO for integration. Circuits detecting environmental warmth are not active, vasoconstriction dominates and BAT is active. AgRP neurons signal hunger and inhibit sleep. (Bottom – Factors promoting NREM sleep) Circadian cues are now permissive for sleep and homeostatic pressure to sleep is high. Behavioural factors also promote sleep and autonomic inputs are permissive for sleep. On seeking shelter and warmth and having eaten, sleep is permitted. Autonomic signals, such as ambient temperature, are relayed via the spine and pass through the LPb to the PO for integration. NOS1-glutamate neurons are activated by skin warmth and initiate both NREM and body cooling. Activation of vasodilatory and BAT downregulation circuits is via NOS1 projections to LPO GABAergic neurons or via direct projections to DMH and rRPA/RVLM. Behavioural inputs are now sleep promoting and may integrate this information in the VTA. Hormonal inputs, such as leptin, are detected in the ARC and are sleep permissive. POMC neurons detect satiety and are permissive for sleep. NO, nitric oxide; NOS1, nitric oxide synthase-1; PO, preoptic area; LPO, lateral preoptic area; vPAG, ventral periaqueductal grey; TMN, tuberomammillary nucleus; VTA, ventral tegmental area; ARC, arcuate nucleus; LPb, lateral parabrachial; LC, locus coeruleus; DR, dorsal raphe; BAT, brown adipose tissue; AgRP, agouti-related peptide; DMH, dorsal medial hypothalamus; rRPA, rostral raphe pallidus; RVLM, rostral ventrolateral medulla; POMC, pro-opiomelanocortin (Leshan et al., 2012; Eban-Rothschild et al., 2016; Weber and Dan, 2016; Yu et al., 2016; Goldstein et al., 2018; Harding et al., 2018; Yu et al., 2019).