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Link to original content: https://pubmed.ncbi.nlm.nih.gov/23508038
The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions - PubMed Skip to main page content
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. 2013 Mar 6:4:18.
doi: 10.3389/fendo.2013.00018. eCollection 2013.

The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions

Ayumu Inutsuka  1 , Akihiro Yamanaka
Affiliations

The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions

Ayumu Inutsuka et al. Front Endocrinol (Lausanne). .

Abstract

The hypothalamus monitors body homeostasis and regulates various behaviors such as feeding, thermogenesis, and sleeping. Orexins (also known as hypocretins) were identified as endogenous ligands for two orphan G-protein-coupled receptors in the lateral hypothalamic area. They were initially recognized as regulators of feeding behavior, but they are mainly regarded as key modulators of the sleep/wakefulness cycle. Orexins activate orexin neurons, monoaminergic and cholinergic neurons in the hypothalamus/brainstem regions, to maintain a long, consolidated awake period. Anatomical studies of neural projections from/to orexin neurons and phenotypic characterization of transgenic mice revealed various roles for orexin neurons in the coordination of emotion, energy homeostasis, reward system, and arousal. For example, orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin, and glucose concentration. This suggests that they may provide a link between energy homeostasis and arousal states. A link between the limbic system and orexin neurons might be important for increasing vigilance during emotional stimuli. Orexins are also involved in reward systems and the mechanisms of drug addiction. These findings suggest that orexin neurons sense the outer and inner environment of the body and maintain the proper wakefulness level of animals for survival. This review discusses the mechanism by which orexins maintain sleep/wakefulness states and how this mechanism relates to other systems that regulate emotion, reward, and energy homeostasis.

Keywords: hypocretin; hypothalamus; neuropeptide; optogenetics; orexin; sleep.

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Figures

FIGURE 1
FIGURE 1
Schematic representation of inputs and outputs of orexin neurons. Orexin neurons are found only in the lateral hypothalamic area but project throughout the entire central nervous system. Red arrows show excitatory projections, while blue lines show inhibitory projections. Abbreviations: Arc, arcuate nucleus; DR, dorsal raphe nucleus; LC, locus coeruleus; LDT, laterodorsal tegmental nucleus; PPT, pedunculopontine tegmental nucleus; TMN, tuberomammillary nucleus; VTA, ventral tegmental area; VLPO, ventrolateral preoptic nucleus.
FIGURE 2
FIGURE 2
A schematic diagram to illustrate the integrative physiological roles of orexin neurons. Orexin neurons regulate various physiological phenomena such as wakefulness, feeding, reward, and thermogenesis. The body energy level influences orexin neuronal activity to coordinate arousal and energy homeostasis. Inputs from the limbic system may be important to regulate the activity of orexin neurons to evoke emotional arousal or fear-related responses. Abbreviations: 5-HT, serotonin; ACh, acetylcholine; Arc, arcuate nucleus; BAT, brown adipose tissue; BST, bed nucleus of the stria terminalis; DA, dopamine; DR, dorsal raphe nucleus; GABA, gamma-aminobutyric acid; HA, histamine; LC, locus coeruleus; LDT, laterodorsal tegmental nucleus; LHA, lateral hypothalamic area; NA, noradrenalin; NAc, nucleus accumbens; NPY, neuropeptide Y; POA, preoptic area; POMC, proopiomelanocortin; PPT, pedunculopontine tegmental nucleus; SCN, suprachiasmatic nucleus; TMN, tuberomammillary nucleus; VTA, ventral tegmental area.
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