2018 Fiscal Year Annual Research Report
The role of the nucleus accumbens in regulating slow-wave sleep by motivated behavior
| Project/Area Number |
17H02215
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ラザルス ミハエル 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80469650)
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| Co-Investigator(Kenkyū-buntansha) |
高田 陽子 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60435740)
斉藤 毅 筑波大学, 国際統合睡眠医科学研究機構, 助教 (80609933)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | Sleep / Motivation / Nucleus accumbens |
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| Outline of Annual Research Achievements |
Sleep and wakefulness are controlled by a wide range of neuronal populations in the mammalian brain.
Activation of adenosine A2A receptor (A2AR)-expressing neurons in the nucleus accumbens (NAc) core promotes slow-wave sleep (SWS). The neuronal mechanism by which activation of NAc A2AR neurons induces SWS, however, is unknown. We hypothesized that the ability of NAc activation to induce sleep is mediated by the classic somnogen adenosine. To investigate whether astrocytes are involved in the ability of the NAc to regulate SWS, we ablated glial fibrillary acidic protein (GFAP)-positive cells in the NAc core of mice by virus-mediated expression of diphtheria toxin (DT) receptors and intraperitoneal administration of DT. Analysis of electroencephalogram and electromyogram recordings of DT-treated wild-type mice revealed that SWS was remarkably increased at 1 week after DT treatment, whereas sleep-wake behavior was unchanged in DT-treated A2AR knockout mice. Cell ablation was associated with an increased number of GFAP-positive cells and activation of microglia in the NAc. In-vivo microdialysis revealed significantly increased levels of extracellular adenosine in the NAc at 1 week after DT treatment. Our findings suggest that elevated adenosine levels in the NAc core promote SWS by acting on A2ARs and provide the first evidence that adenosine is an endogenous candidate for activating NAc A2AR neurons that have the ability to induce SWS.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The project is progressing well and further results of this project have been published in the journal Neurochemistry International.
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| Strategy for Future Research Activity |
We will continue to elucidate the mechanism of the activation of the NAc for sleep control. Glial cells, including astrocytes, may play an important role in regulating extracellular adenosine in the NAc during sleep and wakefulness.
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[Journal Article] Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function2019
Author(s)
Korkutata Mustafa, Saitoh Tsuyoshi, Ioka, Shuji, Feng Duo, Murakoshi Nobuyuki, Fujii Shinya, Zhou Xuzhao, Sugiyama Fumihiro, Chen Jiang-Fan, Kumagai Hidetoshi, Nagase Hiroshi, Lazarus Michael
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Journal Title
Neuropharmacology
Volume: 144
Pages: 122-132
DOI
Peer Reviewed / Int'l Joint Research
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