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Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study
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Sims, Robert E., Wu, Houdini Ho Tin and Dale, Nicholas (2013) Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study. PLoS One, Vol.8 (No.1). e53814. doi:10.1371/journal.pone.0053814 ISSN 1932-6203.
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Official URL: http://dx.doi.org/10.1371/journal.pone.0053814
Abstract
Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QL Zoology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Library of Congress Subject Headings (LCSH): | Adenosine, Sleep -- Physiological aspects, Rodents -- Physiology | ||||
Journal or Publication Title: | PLoS One | ||||
Publisher: | Public Library of Science | ||||
ISSN: | 1932-6203 | ||||
Official Date: | January 2013 | ||||
Dates: |
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Volume: | Vol.8 | ||||
Number: | No.1 | ||||
Page Range: | e53814 | ||||
DOI: | 10.1371/journal.pone.0053814 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 23 December 2015 | ||||
Date of first compliant Open Access: | 23 December 2015 | ||||
Funder: | Wellcome Trust (London, England) | ||||
Grant number: | WT087968MA (WT) |
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