Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice

Abstract The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes...

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Autores principales:	Chun Yang, Andrei Larin, James T. McKenna, Kenneth A. Jacobson, Stuart Winston, Robert E. Strecker, Anna Kalinchuk, Radhika Basheer, Ritchie E. Brown
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b3e1e1e253041a2bc951220bd9dc89a
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spelling	oai:doaj.org-article:7b3e1e1e253041a2bc951220bd9dc89a2021-12-02T15:07:49ZActivation of basal forebrain purinergic P2 receptors promotes wakefulness in mice10.1038/s41598-018-29103-42045-2322https://doaj.org/article/7b3e1e1e253041a2bc951220bd9dc89a2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29103-4https://doaj.org/toc/2045-2322Abstract The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes sleep. Infusion of a non-hydrolysable P2R agonist, ATP-γ-S, into mouse BF increased wakefulness following sleep deprivation. ATP-γ-S depolarized BF cholinergic and cortically-projecting GABAergic neurons in vitro, an effect blocked by antagonists of ionotropic P2Rs (P2XRs) or glutamate receptors. In vivo, ATP-γ-S infusion increased BF glutamate release. Thus, activation of BF P2XRs promotes glutamate release and excitation of wake-active neurons. Conversely, pharmacological antagonism of BF P2XRs decreased spontaneous wakefulness during the dark (active) period. Together with previous findings, our results suggest sleep-wake regulation by BF extracellular ATP involves a balance between excitatory, wakefulness-promoting effects mediated by direct activation of P2XRs and inhibitory, sleep-promoting effects mediated by degradation to adenosine.Chun YangAndrei LarinJames T. McKennaKenneth A. JacobsonStuart WinstonRobert E. StreckerAnna KalinchukRadhika BasheerRitchie E. BrownNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chun Yang Andrei Larin James T. McKenna Kenneth A. Jacobson Stuart Winston Robert E. Strecker Anna Kalinchuk Radhika Basheer Ritchie E. Brown Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
description	Abstract The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes sleep. Infusion of a non-hydrolysable P2R agonist, ATP-γ-S, into mouse BF increased wakefulness following sleep deprivation. ATP-γ-S depolarized BF cholinergic and cortically-projecting GABAergic neurons in vitro, an effect blocked by antagonists of ionotropic P2Rs (P2XRs) or glutamate receptors. In vivo, ATP-γ-S infusion increased BF glutamate release. Thus, activation of BF P2XRs promotes glutamate release and excitation of wake-active neurons. Conversely, pharmacological antagonism of BF P2XRs decreased spontaneous wakefulness during the dark (active) period. Together with previous findings, our results suggest sleep-wake regulation by BF extracellular ATP involves a balance between excitatory, wakefulness-promoting effects mediated by direct activation of P2XRs and inhibitory, sleep-promoting effects mediated by degradation to adenosine.
format	article
author	Chun Yang Andrei Larin James T. McKenna Kenneth A. Jacobson Stuart Winston Robert E. Strecker Anna Kalinchuk Radhika Basheer Ritchie E. Brown
author_facet	Chun Yang Andrei Larin James T. McKenna Kenneth A. Jacobson Stuart Winston Robert E. Strecker Anna Kalinchuk Radhika Basheer Ritchie E. Brown
author_sort	Chun Yang
title	Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
title_short	Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
title_full	Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
title_fullStr	Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
title_full_unstemmed	Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice
title_sort	activation of basal forebrain purinergic p2 receptors promotes wakefulness in mice
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7b3e1e1e253041a2bc951220bd9dc89a
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Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice

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