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Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice

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Jagannath, Aarti, Varga, Norbert, Dallmann, Robert, Rando, Gianpaolo, Gosselin, Pauline, Ebrahimjee, Farid, Taylor, Lewis, Mosneagu, Dragos, Stefaniak, Jakub, Walsh, Steven et al.
(2021) Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nature Communications, 12 (1). 2113. doi:10.1038/s41467-021-22179-z

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Official URL: https://doi.org/10.1038/s41467-021-22179-z

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Abstract

Abstract: The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice.

Item Type: Journal Article
Subjects: Q Science > QL Zoology
Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Adenosine , Adenosine -- Receptors, Sleep -- Physiological aspects , Sleep disorders, Sleep behavior in animals, Circadian rhythm, Circadian rhythm -- Animal models
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group UK
ISSN: 2041-1723
Official Date: 9 April 2021
Dates:
DateEvent
9 April 2021Published
18 February 2021Accepted
Volume: 12
Number: 1
Article Number: 2113
DOI: 10.1038/s41467-021-22179-z
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/N01992X/1 [BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
WT106174/Z/14/ZMA Wellcome Trusthttp://dx.doi.org/10.13039/100010269
BB/N001664/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDJohn Fell Fund, University of Oxfordhttp://dx.doi.org/10.13039/501100004789
NS103740 National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
NS065957National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
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