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Published in: Brain Structure and Function 3/2017

01-04-2017 | Original Article

Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents

Authors: Yi-Qun Wang, Rui Li, Dian-Ru Wang, Yoan Cherasse, Ze Zhang, Meng-Qi Zhang, Oriana Lavielle, Kristopher McEown, Serge N. Schiffmann, Alban de Kerchove d’Exaerde, Wei-Min Qu, Michael Lazarus, Zhi-Li Huang

Published in: Brain Structure and Function | Issue 3/2017

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Abstract

Rapid eye movement (REM) sleep behavior disorder in humans is often accompanied by a reduced ability to smell and detect odors, and olfactory bulbectomized rats exhibit increased REM sleep, suggesting that the olfactory bulb (OB) is involved in REM-sleep regulation. However, the molecular mechanism of REM-sleep regulation by the OB is unknown. Adenosine promotes sleep and its A2A receptors (A2AR) are expressed in the OB. We hypothesized that A2AR in the OB regulate REM sleep. Bilateral microinjections of the A2AR antagonist SCH58261 into the rat OB increased REM sleep, whereas microinjections of the A2AR agonist CGS21680 decreased REM sleep. Similar to the A2AR antagonist, selective A2AR knockdown by adeno-associated virus carrying short-hairpin RNA for A2AR in the rat OB increased REM sleep. Using chemogenetics on the basis of designer receptors exclusively activated by designer drugs, we demonstrated that the inhibition of A2AR neurons increased REM sleep, whereas the activation of these neurons decreased REM sleep. Moreover, using a conditional anterograde axonal tract-tracing approach, we found that OB A2AR neurons innervate the piriform cortex and olfactory tubercle. These novel findings indicate that adenosine suppresses REM sleep via A2AR in the OB of rodents.
Literature
go back to reference Carskadon MA, Herz RS (2004) Minimal olfactory perception during sleep: why odor alarms will not work for humans. Sleep 27(3):402–405PubMed Carskadon MA, Herz RS (2004) Minimal olfactory perception during sleep: why odor alarms will not work for humans. Sleep 27(3):402–405PubMed
go back to reference Doengi M, Deitmer JW, Lohr C (2008) New evidence for purinergic signaling in the olfactory bulb: A2A and P2Y1 receptors mediate intracellular calcium release in astrocytes. FASEB J 22(7):2368–2378. doi:10.1096/fj.07-101782 CrossRef Doengi M, Deitmer JW, Lohr C (2008) New evidence for purinergic signaling in the olfactory bulb: A2A and P2Y1 receptors mediate intracellular calcium release in astrocytes. FASEB J 22(7):2368–2378. doi:10.​1096/​fj.​07-101782 CrossRef
go back to reference Durieux PF, Bearzatto B, Guiducci S, Buch T, Waisman A, Zoli M, Schiffmann SN, de Kerchove d’Exaerde A (2009) D2R striatopallidal neurons inhibit both locomotor and drug reward processes. Nat Neurosci 12(4):393–395. doi:10.1038/nn.2286 CrossRefPubMed Durieux PF, Bearzatto B, Guiducci S, Buch T, Waisman A, Zoli M, Schiffmann SN, de Kerchove d’Exaerde A (2009) D2R striatopallidal neurons inhibit both locomotor and drug reward processes. Nat Neurosci 12(4):393–395. doi:10.​1038/​nn.​2286 CrossRefPubMed
go back to reference Durieux PF, Schiffmann SN, de Kerchove d’Exaerde A (2012) Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. EMBO J 31(3):640–653. doi:10.1038/emboj.2011.400 CrossRefPubMed Durieux PF, Schiffmann SN, de Kerchove d’Exaerde A (2012) Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. EMBO J 31(3):640–653. doi:10.​1038/​emboj.​2011.​400 CrossRefPubMed
go back to reference Ena SL, De Backer JF, Schiffmann SN, de Kerchove d’Exaerde A (2013) FACS array profiling identifies Ecto-5′ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci 33(20):8794–8809. doi:10.1523/JNEUROSCI.2989-12.2013 CrossRef Ena SL, De Backer JF, Schiffmann SN, de Kerchove d’Exaerde A (2013) FACS array profiling identifies Ecto-5′ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci 33(20):8794–8809. doi:10.​1523/​JNEUROSCI.​2989-12.​2013 CrossRef
go back to reference Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE (2001) Fos expression in orexin neurons varies with behavioral state. J Neurosci 21(5):1656–1662PubMed Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE (2001) Fos expression in orexin neurons varies with behavioral state. J Neurosci 21(5):1656–1662PubMed
go back to reference Gautron L, Lazarus M, Scott MM, Saper CB, Elmquist JK (2010) Identifying the efferent projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach. J Comp Neurol 518(11):2090–2108. doi:10.1002/cne.22323 CrossRefPubMedPubMedCentral Gautron L, Lazarus M, Scott MM, Saper CB, Elmquist JK (2010) Identifying the efferent projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach. J Comp Neurol 518(11):2090–2108. doi:10.​1002/​cne.​22323 CrossRefPubMedPubMedCentral
go back to reference Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8(7):858–859. doi:10.1038/nn1491 CrossRefPubMed Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8(7):858–859. doi:10.​1038/​nn1491 CrossRefPubMed
go back to reference Huang ZL, Urade Y, Hayaishi O (2011) The role of adenosine in the regulation of sleep. Curr Top Med Chem 11(8):1047–1057CrossRefPubMed Huang ZL, Urade Y, Hayaishi O (2011) The role of adenosine in the regulation of sleep. Curr Top Med Chem 11(8):1047–1057CrossRefPubMed
go back to reference Jego S, Glasgow SD, Herrera CG, Ekstrand M, Reed SJ, Boyce R, Friedman J, Burdakov D, Adamantidis AR (2013) Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci 16(11):1637–1643. doi:10.1038/nn.3522 CrossRefPubMedPubMedCentral Jego S, Glasgow SD, Herrera CG, Ekstrand M, Reed SJ, Boyce R, Friedman J, Burdakov D, Adamantidis AR (2013) Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci 16(11):1637–1643. doi:10.​1038/​nn.​3522 CrossRefPubMedPubMedCentral
go back to reference Johansson B, Georgiev V, Fredholm BB (1997) Distribution and postnatal ontogeny of adenosine A2A receptors in rat brain: comparison with dopamine receptors. Neuroscience 80(4):1187–1207CrossRefPubMed Johansson B, Georgiev V, Fredholm BB (1997) Distribution and postnatal ontogeny of adenosine A2A receptors in rat brain: comparison with dopamine receptors. Neuroscience 80(4):1187–1207CrossRefPubMed
go back to reference Kaelin-Lang A, Lauterburg T, Burgunder JM (1999) Expression of adenosine A2a receptors gene in the olfactory bulb and spinal cord of rat and mouse. Neurosci Lett 261(3):189–191CrossRefPubMed Kaelin-Lang A, Lauterburg T, Burgunder JM (1999) Expression of adenosine A2a receptors gene in the olfactory bulb and spinal cord of rat and mouse. Neurosci Lett 261(3):189–191CrossRefPubMed
go back to reference Kalinchuk AV, Urrila AS, Alanko L, Heiskanen S, Wigren HK, Suomela M, Stenberg D, Porkka-Heiskanen T (2003) Local energy depletion in the basal forebrain increases sleep. Eur J Neurosci 17(4):863–869CrossRefPubMed Kalinchuk AV, Urrila AS, Alanko L, Heiskanen S, Wigren HK, Suomela M, Stenberg D, Porkka-Heiskanen T (2003) Local energy depletion in the basal forebrain increases sleep. Eur J Neurosci 17(4):863–869CrossRefPubMed
go back to reference Kugler S, Kilic E, Bahr M (2003) Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area. Gene Ther 10(4):337–347. doi:10.1038/sj.gt.3301905 CrossRefPubMed Kugler S, Kilic E, Bahr M (2003) Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area. Gene Ther 10(4):337–347. doi:10.​1038/​sj.​gt.​3301905 CrossRefPubMed
go back to reference Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31(27):10067–10075. doi:10.1523/JNEUROSCI.6730-10.2011 CrossRefPubMedCentral Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31(27):10067–10075. doi:10.​1523/​JNEUROSCI.​6730-10.​2011 CrossRefPubMedCentral
go back to reference Leite-Panissi CR, Coimbra NC, Menescal-de-Oliveira L (2003) The cholinergic stimulation of the central amygdala modifying the tonic immobility response and antinociception in guinea pigs depends on the ventrolateral periaqueductal gray. Brain Res Bull 60(1–2):167–178CrossRefPubMed Leite-Panissi CR, Coimbra NC, Menescal-de-Oliveira L (2003) The cholinergic stimulation of the central amygdala modifying the tonic immobility response and antinociception in guinea pigs depends on the ventrolateral periaqueductal gray. Brain Res Bull 60(1–2):167–178CrossRefPubMed
go back to reference Mavanji V, Siwek DF, Patterson EH, Spoley EE, Datta S (2003) Effects of passive-avoidance training on sleep-wake state-specific activity in the basolateral and central nuclei of the amygdala. Behav Neurosci 117(4):751–759CrossRefPubMed Mavanji V, Siwek DF, Patterson EH, Spoley EE, Datta S (2003) Effects of passive-avoidance training on sleep-wake state-specific activity in the basolateral and central nuclei of the amygdala. Behav Neurosci 117(4):751–759CrossRefPubMed
go back to reference Miyamichi K, Amat F, Moussavi F, Wang C, Wickersham I, Wall NR, Taniguchi H, Tasic B, Huang ZJ, He Z, Callaway EM, Horowitz MA, Luo L (2011) Cortical representations of olfactory input by trans-synaptic tracing. Nature 472(7342):191–196. doi:10.1038/nature09714 CrossRefPubMed Miyamichi K, Amat F, Moussavi F, Wang C, Wickersham I, Wall NR, Taniguchi H, Tasic B, Huang ZJ, He Z, Callaway EM, Horowitz MA, Luo L (2011) Cortical representations of olfactory input by trans-synaptic tracing. Nature 472(7342):191–196. doi:10.​1038/​nature09714 CrossRefPubMed
go back to reference Oishi Y, Takata Y, Taguchi Y, Kohtoh S, Urade Y, Lazarus M (2016) Polygraphic recording procedure for measuring sleep in mice. J Vis Exp 107:e53678. doi:10.3791/53678 Oishi Y, Takata Y, Taguchi Y, Kohtoh S, Urade Y, Lazarus M (2016) Polygraphic recording procedure for measuring sleep in mice. J Vis Exp 107:e53678. doi:10.​3791/​53678
go back to reference Pawlyk AC, Sanford LD, Brennan FX, Morrison AR, Ross RJ (2006) Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep. Pharmacol Rep 58(1):125–130PubMed Pawlyk AC, Sanford LD, Brennan FX, Morrison AR, Ross RJ (2006) Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep. Pharmacol Rep 58(1):125–130PubMed
go back to reference Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier, Boston Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier, Boston
go back to reference Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276(5316):1265–1268CrossRefPubMedPubMedCentral Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276(5316):1265–1268CrossRefPubMedPubMedCentral
go back to reference Scammell TE, Gerashchenko DY, Mochizuki T, McCarthy MT, Estabrooke IV, Sears CA, Saper CB, Urade Y, Hayaishi O (2001) An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience 107(4):653–663CrossRefPubMed Scammell TE, Gerashchenko DY, Mochizuki T, McCarthy MT, Estabrooke IV, Sears CA, Saper CB, Urade Y, Hayaishi O (2001) An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience 107(4):653–663CrossRefPubMed
go back to reference Treloar HB, Miller AM, Ray A, Greer CA (2010) Development of the olfactory system. In: Menini A (ed) The neurobiology of olfaction. Frontiers in Neuroscience. CRC Press, Boca Raton Treloar HB, Miller AM, Ray A, Greer CA (2010) Development of the olfactory system. In: Menini A (ed) The neurobiology of olfaction. Frontiers in Neuroscience. CRC Press, Boca Raton
go back to reference Urade Y, Eguchi N, Qu WM, Sakata M, Huang ZL, Chen JF, Schwarzschild MA, Fink JS, Hayaishi O (2003) Sleep regulation in adenosine A2A receptor-deficient mice. Neurology 61(11 Suppl 6):S94–S96CrossRefPubMed Urade Y, Eguchi N, Qu WM, Sakata M, Huang ZL, Chen JF, Schwarzschild MA, Fink JS, Hayaishi O (2003) Sleep regulation in adenosine A2A receptor-deficient mice. Neurology 61(11 Suppl 6):S94–S96CrossRefPubMed
go back to reference Weaver DR (1993) A2a adenosine receptor gene expression in developing rat brain. Brain Res Mol Brain Res 20(4):313–327CrossRefPubMed Weaver DR (1993) A2a adenosine receptor gene expression in developing rat brain. Brain Res Mol Brain Res 20(4):313–327CrossRefPubMed
go back to reference Zhang JP, Xu Q, Yuan XS, Cherasse Y, Schiffmann SN, de Kerchove d’Exaerde A, Qu WM, Urade Y, Lazarus M, Huang ZL, Li RX (2013) Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation. Front Neuroanat 7:43. doi:10.3389/fnana.2013.00043 CrossRefPubMedPubMedCentral Zhang JP, Xu Q, Yuan XS, Cherasse Y, Schiffmann SN, de Kerchove d’Exaerde A, Qu WM, Urade Y, Lazarus M, Huang ZL, Li RX (2013) Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation. Front Neuroanat 7:43. doi:10.​3389/​fnana.​2013.​00043 CrossRefPubMedPubMedCentral
Metadata
Title
Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents
Authors
Yi-Qun Wang
Rui Li
Dian-Ru Wang
Yoan Cherasse
Ze Zhang
Meng-Qi Zhang
Oriana Lavielle
Kristopher McEown
Serge N. Schiffmann
Alban de Kerchove d’Exaerde
Wei-Min Qu
Michael Lazarus
Zhi-Li Huang
Publication date
01-04-2017
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 3/2017
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-016-1281-2

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