Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions

Matthew E. Carter, Antoine Adamantidis, Hiroshi Ohtsu, Karl Deisseroth, Luis De Lecea

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)

Abstract

The hypocretins (Hcrts) (also called orexins) are two neuropeptides expressed in the lateral hypothalamus that play a crucial role in the stability of wakefulness. Previously, our laboratory demonstrated that in vivo photostimulation of Hcrt neurons genetically targeted with ChR2, a light-activated cation channel, was sufficient to increase the probability of an awakening event during both slow-wave sleep and rapid eye movement sleep. In the current study,weask whether Hcrt-mediated sleep-to-wake transitions are affected by light/dark period and sleep pressure. We found that stimulation of Hcrt neurons increased the probability of an awakening event throughout the entire light/dark period but that this effect was diminished with sleep pressure induced by 2 or 4 h of sleep deprivation. Interestingly, photo-stimulation of Hcrt neurons was still sufficient to increase activity assessed by c-Fos expression in Hcrt neurons after sleep deprivation, although this stimulation did not cause an increase in transitions to wakefulness. In addition, we found that photo-stimulation of Hcrt neurons increases neural activity assessed by c-Fos expression in the downstream arousal-promoting locus ceruleus and tuberomammilary nucleus but not after 2 h of sleep deprivation. Finally, stimulation of Hcrt neurons was still sufficient to increase the probability of an awakening event in histidine decarboxylase-deficient knock-out animals. Collectively, these results suggest that the Hcrt system promotes wakefulness throughout the light/dark period by activating multiple downstream targets, which themselves are inhibited with increased sleep pressure.

Original languageEnglish
Pages (from-to)10939-10949
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number35
DOIs
Publication statusPublished - 2009 Sep 2
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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