Brain Structure and Function

, Volume 222, Issue 3, pp 1351–1366 | Cite as

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

  • 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 QuEmail author
  • Michael LazarusEmail author
  • Zhi-Li HuangEmail author
Original Article


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.


A2AR-Cre mice Chemogenetics REM-sleep behavior disorder Short-hairpin RNA 



This study was supported in part by grants-in-aid for scientific research from the National Natural Science Foundation of China (81571295, 31530035, 31471064, 31271164, and 81420108015); the National Basic Research Program of China (2015CB856401 and 2011CB711000); a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005); the Shanghai Committee of Science and Technology (14JC1400900); the Japan Society for the Promotion of Science (KAKENHI Grant 2604762); the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Grant for Scientific Research on Innovative Areas “Living in Space”, 16H01629); the World Premier International Research Center Initiative (WPI) from MEXT; FMRE-Belgium; FRS–FNRS, Belgium; Interuniversity Attraction Pole (IUAP—P7/10) from Belgian Federal Scientific Affairs, and Action de Recherche Concertée (FWB).

Compliance with ethical standards

Conflict of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Yi-Qun Wang
    • 1
  • Rui Li
    • 1
  • Dian-Ru Wang
    • 1
  • Yoan Cherasse
    • 2
  • Ze Zhang
    • 1
  • Meng-Qi Zhang
    • 1
  • Oriana Lavielle
    • 2
  • Kristopher McEown
    • 2
  • Serge N. Schiffmann
    • 3
  • Alban de Kerchove d’Exaerde
    • 3
  • Wei-Min Qu
    • 1
    Email author
  • Michael Lazarus
    • 2
    Email author
  • Zhi-Li Huang
    • 1
    Email author
  1. 1.Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain ScienceFudan UniversityShanghaiChina
  2. 2.International Institute for Integrative Sleep Medicine (WPI-IIIS)University of TsukubaTsukubaJapan
  3. 3.Laboratory of Neurophysiology, ULB Neuroscience InstituteUniversité Libre de BruxellesBrusselsBelgium

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