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Cellular energy dynamics in orexin neurons across sleep-wake cycle

Research Project

Project/Area Number 18K14756
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

NATSUBORI Akiyo  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (20732837)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアデノシン3リン酸 (ATP) / 睡眠覚醒 / ファイバフォトメトリー / 生体脳計測 / アデノシン三リン酸 / 生体計測 / アデノシン3リン酸 / in vivo / アデノシン3リン酸 (ATP) / オレキシン神経 / インビボ計測
Outline of Final Research Achievements

As one of the regulators of membrane excitability of sleep or arousal-related neurons in animals, the intracellular concentrations of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, could be involved. In order to test this hypothesis, we conducted in vivo optical recording of intracellular ATP concentration in the lateral hypothalamus, where the orexin neurons involved in arousal is localized, using a genetically encoded fluorescent ATP sensor. With fiber photometric recordings, we observed that intracellular ATP concentrations in the lateral hypothalamus increased during non-REM sleep compared to awake, while a great decrease was observed during REM-sleep of animals. These results showed that intracellular ATP concentrations fluctuates depending on the sleep-wake state of animals. These state-dependent ATP fluctuations could affect neuronal membrane excitability under physiological conditions.

Academic Significance and Societal Importance of the Research Achievements

本研究は、動物の睡眠覚醒に合わせ、細胞のエネルギー分子であるATP(アデノシン3リン酸)が脳内で生理的に変動していることを、マウスを用いた生体計測により明らかにした。特に、動物の覚醒を引き起こす中枢領域である外側視床下部において細胞内ATP濃度が変動していたことから、細胞内ATPが覚醒中枢神経の活動を調節する新たな因子として機能している可能性が予想できる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Neuroimaging correlates of narcolepsy with cataplexy: A systematic review.2019

    • Author(s)
      Wada M, Mimura M, Noda Y, Takasu S, Plitman E, Honda M, Natsubori A, Ogyu K, Tarumi R, Graff-Guerrero A, Nakajima S.
    • Journal Title

      Neurosci Res.

      Volume: 142 Pages: 16-29

    • DOI

      10.1016/j.neures.2018.03.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In vivo optical recording reveal state-dependent intracellular ATP dynamics in neurons2019

    • Author(s)
      夏堀 晃世
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] In vivo dynamics of cortical neuronal intracellular ATP levels.2019

    • Author(s)
      夏堀 晃世
    • Organizer
      Optogenetics2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 睡眠覚醒に伴う大脳皮質の細胞内ATP動態の解明2018

    • Author(s)
      夏堀 晃世
    • Organizer
      日本睡眠学会第43回定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The intracellular ATP dynamics in the cerebral cortex is closely related to the neurometabolic coupling2018

    • Author(s)
      Akiyo Natsubori, Akihiro Karashima, Takashi Kojima, Toru Kodama, Kazuto Masamoto, Norio Takata, Kenji F Tanaka, Masamichi Yamamoto, Makoto Honda
    • Organizer
      Sapporo Symposium on Biological Rhythm in 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 公益財団法人 東京都医学総合研究所 睡眠プロジェクト

    • URL

      http://www.igakuken.or.jp/sleep/index.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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