AUTHOR=De Lecea Luis , Huerta Ramon TITLE=Hypocretin (orexin) regulation of sleep-to-wake transitions JOURNAL=Frontiers in Pharmacology VOLUME=Volume 5 - 2014 YEAR=2014 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00016 DOI=10.3389/fphar.2014.00016 ISSN=1663-9812 ABSTRACT=The hypocretin (Hcrt), also known as orexin, peptides are essential for arousal stability. Here I discuss background information about the interaction of Hcrt with other neuromodulators, including norepinephrine and acetylcholine probed with optogenetics. I 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.