Hypocretin (orexin) regulation of sleep-to-wake transitions

Abstract

The hypocretin (Hcrt), also known as orexin, peptides are essential for arousal stability. Here we discuss background information about the interaction of Hcrt with other neuromodulators, including norepinephrine and acetylcholine probed with optogenetics. We conclude that Hcrt neurons integrate metabolic, circadian and limbic inputs and convey this information to a network of neuromodulators, each of which has a different role on the dynamic of sleep-to-wake transitions. This model may prove useful to predict the effects of orexin receptor antagonists in sleep disorders and other conditions.

7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice

“…Orexins including Orexin A and Orexin B (also called hypocretin 1 and hypocretin 2) have long been recognized as peptides that promote wakefulness and suppress sleep (de Lecea and Huerta, 2014, Sakurai et al , 2010, Saper, 2013. Both Orexin A and Orexin B exposure significantly increases Neurotrophin-3 (NT-3) mRNA.…”

Alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness

“…These neuropeptides, cleaved from the common precursor prepro-orexin, are largely co-localized in the same neurons (Nixon and Smale, 2007), and OX-A is more stable than OX-B. Orexinergic innervation is widely distributed in the CNS, and the orexinergic system has been implicated in a variety of functions, especially the regulation of feeding and energy homeostasis, as well as sleep-wake state transitions and arousal stability (Sakurai, 2007;Ohno and Sakurai, 2008;Sakurai and Mieda, 2011;Kukkonen, 2013;Jones and Hassani, 2013;de Lecea and Huerta, 2014).…”

0934 Evaluating the Effects of General Anesthesia on Sleep in Children Undergoing Elective Surgery

“…As orexin stabilizes wakefulness through activation of noradrenergic neurons in the LC, an increase in wakefulness and decrease in NREM sleep was observed following ketamine anesthesia (de Lecea & Huerta, 2014). In contrast, rats showed reduced wakefulness and an increase in NREM sleep following propofol anesthesia.…”