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

Carter, Matthew E; Adamantidis, Antoine Roger; Ohtsu, Hiroshi; Deisseroth, Karl; de Lecea, Luis (2009). Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. Journal of neuroscience, 29(35), pp. 10939-10949. Society for Neuroscience 10.1523/JNEUROSCI.1205-09.2009

[img] Text
10939.full.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (2MB) | Request a copy

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, we ask 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, photostimulation 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 photostimulation 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Adamantidis, Antoine Roger

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0270-6474

Publisher:

Society for Neuroscience

Language:

English

Submitter:

Stefanie Hetzenecker

Date Deposited:

11 Jul 2018 15:55

Last Modified:

27 Oct 2019 07:41

Publisher DOI:

10.1523/JNEUROSCI.1205-09.2009

PubMed ID:

19726652

BORIS DOI:

10.7892/boris.117266

URI:

https://boris.unibe.ch/id/eprint/117266

Actions (login required)

Edit item Edit item
Provide Feedback