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Behavior control by manipulating neurocircuit using optogenetics and/or chemicogenetics

開催日 2014/9/12
時間 17:10 - 19:10
会場 Room B(501)
Chairperson(s) 成塚 裕美 / Hiromi Naritsuka (東京大学大学院 医学系研究科 細胞分子生理学教室 / Department of Physiology, Graduate School of Medicine, University of Tokyo, Japan)
山中 章弘 / Akihiro Yamanaka (名古屋大学環境医学研究所 / Research Institute of Environmental Medicine, Nagoya University, Japan)

The role of adenosine A 2A receptors in the nucleus accumbens for the control of sleep and wakefulness

  • S2-B-3-2
  • Michael Lazarus:1 
  • 1:International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Japan 

The fundamental governing principles for the regulation of sleep are incompletely understood and neural substrates that, when activated, promote non-rapid eye movement (non-REM, NREM) sleep, also known as slow wave sleep, remain to be identified. The motivation to defy sleep and stay awake for a wide range of life-style choices is often accompanied by the use of psychoactive substances, most prominently caffeine. We have revealed that caffeine induces wakefulness by blocking adenosine A2A receptors (A2ARs) in the nucleus accumbens (NAc) (J Neurosci, doi: 10.1523/JNEUROSCI.6730-10.2011). Adenosine promotes sleep and for caffeine to be effective as an antagonist and cause arousal, excitatory A2ARs must be tonically activated by endogenous adenosine. A2ARs are highly expressed on neurons of the NAc that also express dopamine D2 receptors (D2Rs) and enkephalin (Enk), but the extent to which those A2AR/D2R/Enk-positive neurons in the NAc contribute to the regulation of sleep is not known. Optogenetic and pharmacogenetic activation of A2AR neurons in the NAc induces robust NREM sleep. Selective deletion of A2ARs in the NAc leads to increased nocturnal arousal and pharmacological activation of A2ARs by the agonist CGS21680 increased NREM sleep in wild type, but not NAc-specific A2AR knockout mice. Our observations provide direct evidence that adenosine and A2AR neurons in the NAc are not only involved in promoting behavioral inactivity (inhibition of movement), but also play a major role in the regulation of sleep. These findings further suggest the intriguing possibility that the ventral striatum may be a key site through which sleep and wakefulness are regulated by behavioral processes and, by extension, that motivational state may be an important fundamental regulator of sleep and wake (Trends Neurosci, doi: 10.1016/j.tins.2012.07.001).

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