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

<p>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 cir...

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Main Authors: Jagannath, A, Varga, N, Dallmann, R, Vasudevan, S, Foster, R, Et al.
Format: Journal article
Language:English
Published: Nature Research 2021
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author Jagannath, A
Varga, N
Dallmann, R
Vasudevan, S
Foster, R
Et al.
author_facet Jagannath, A
Varga, N
Dallmann, R
Vasudevan, S
Foster, R
Et al.
author_sort Jagannath, A
collection OXFORD
description <p>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 A<sub>1</sub>/A<sub>2A</sub>&nbsp;receptor signalling through the activation of the Ca<sup>2+</sup>&thinsp;-ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes&nbsp;<em>Per1</em>&nbsp;and&nbsp;<em>Per2</em>. 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.</p>
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spelling oxford-uuid:fd6866d3-34cf-47ff-8ba4-edc903333f512022-03-27T13:28:39ZAdenosine integrates light and sleep signalling for the regulation of circadian timing in miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fd6866d3-34cf-47ff-8ba4-edc903333f51EnglishSymplectic ElementsNature Research2021Jagannath, AVarga, NDallmann, RVasudevan, SFoster, REt al.<p>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 A<sub>1</sub>/A<sub>2A</sub>&nbsp;receptor signalling through the activation of the Ca<sup>2+</sup>&thinsp;-ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes&nbsp;<em>Per1</em>&nbsp;and&nbsp;<em>Per2</em>. 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.</p>
spellingShingle Jagannath, A
Varga, N
Dallmann, R
Vasudevan, S
Foster, R
Et al.
Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title_full Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title_fullStr Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title_full_unstemmed Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title_short Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
title_sort adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
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