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報酬系による睡眠制御メカニズムの解明

Research Project

Project/Area Number 18H02534
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

大石 陽  筑波大学, 国際統合睡眠医科学研究機構, 助教 (70554004)

Co-Investigator(Kenkyū-buntansha) 長谷川 恵美  筑波大学, 医学医療系, 助教 (40765955)
シェラス ヨアン  筑波大学, 医学医療系, 研究員 (60544319)
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)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords睡眠 / ドーパミン / GABA / VTA / VMP
Outline of Annual Research Achievements

我々の睡眠覚醒は様々な要因に制御されるが、情動的要因による睡眠制御の脳内メカニズムはほぼ不明である。研究代表者らはごく最近、モチベーション・報酬に関与する脳部位・腹側被蓋野および側坐核が、睡眠制御に重要であることを見出した。しかしながら睡眠調節に関してこれらの報酬系システムを取り巻く神経メカニズムには不明な点が多い。研究代表者らはすでに、腹側被蓋野を調節する腹側中脳、側坐核が制御する腹側淡蒼球を睡眠関連部位として同定している。本研究では両部位に注目し、睡眠制御に関わる詳細な解析を目的とする。具体的には、睡眠アッセイシステム、光遺伝学、化学遺伝学、細胞種特異的神経トレーシング、in vivo神経活性測定など様々な手法を用いて、腹側中脳および腹側淡蒼球の睡眠調節における機能を解析し、報酬系による睡眠制御メカニズム全容の解明を目指す。
今年度も引き続き、腹側被蓋野を調節しうる脳領域として腹側内側中脳橋(ventral medial midbrain/pons area; VMP)に注目し、その睡眠覚醒およびその他の行動における役割を解析した。これまでにVMP GABA作動性神経の選択的欠損に伴う睡眠減少がドーパミンD2受容体に大きく依存することが判明していたため、睡眠以外の行動変化、すなわち多動性や抗うつ様行動に関してD2受容体の重要性を解析した。その結果、D2受容体欠損マウスにおいてもtail suspension testやforced swim testで評価される抗うつ行動が野生型マウスと同様に確認されたため、VMP GABA作動性神経の選択的欠損に伴う抗うつ様行動の亢進にはD2受容体が関与しないことが示唆された。さらに、睡眠減少にはD2受容体が関与することから、この欠損条件では、睡眠減少と抗うつ様行動の亢進が別のメカニズムとして説明できることが示された。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

ドーパミン受容体の重要性などを明らかにでき、研究は計画通りに進行している。

Strategy for Future Research Activity

光遺伝学、化学遺伝学、細胞種特異的神経トレーシング、in vivo神経活性測定などを用いて、VMPの睡眠制御およびその他の行動における機能をさらに詳細に解
析する。

Report

(4 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(12 results)

All 2022 2020 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D2R-mediated Sleep Reduction2020

    • Author(s)
      Honda Takato, Takata Yohko, Cherasse Yoan, Mizuno Seiya, Sugiyama Fumihiro, Takahashi Satoru, Funato Hiromasa, Yanagisawa Masashi, Lazarus Michael, Oishi Yo
    • Journal Title

      iScience

      Volume: 23 Pages: 101240-101240

    • DOI

      10.1016/j.isci.2020.101240

    • NAID

      120007163338

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L-PGDS-produced PGD2 in premature, but not in mature, adipocytes increases obesity and insulin resistance.2019

    • Author(s)
      Fujimori K, Aritake K, Oishi Y, Nagata N, Maehara T, Lazarus M, Urade Y.
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 1931-1931

    • DOI

      10.1038/s41598-018-38453-y

    • NAID

      120007128200

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gating and the Need for Sleep: Dissociable Effects of Adenosine A1 and A2A Receptors2019

    • Author(s)
      Lazarus Michael、Oishi Yo、Bjorness Theresa E.、Greene Robert W.
    • Journal Title

      Frontiers in Neuroscience

      Volume: 13 Pages: 740-740

    • DOI

      10.3389/fnins.2019.00740

    • NAID

      120007133182

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular adenosine and slow-wave sleep are increased after ablation of nucleus accumbens core astrocytes and neurons in mice2019

    • Author(s)
      Zhou X, Oishi Y, Cherasse Y, Korkutata M, Fujii S, Lee CY, Lazarus M
    • Journal Title

      Neurochem Int

      Volume: 124 Pages: 256-263

    • DOI

      10.1016/j.neuint.2019.01.020

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The leptomeninges produce prostaglandin D2 involved in sleep regulation in mice.2018

    • Author(s)
      Cherasse Y, Aritake K, Oishi Y, Kaushik M.K, Korkutata M, Urade Y.
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 12 Pages: 357-357

    • DOI

      10.3389/fncel.2018.00357

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sleep and wakefulness are controlled by ventral medial midbrain/pons GABAergic neurons in mice2018

    • Author(s)
      Takata Y, Oishi Y, Zhou XZ, Hasegawa E, Takahashi K, Cherasse Y, Sakurai T, Lazarus M
    • Journal Title

      The Journal of Neuroscience

      Volume: 0598-18 Pages: 10080-10092

    • DOI

      10.1523/jneurosci.0598-18.2018

    • NAID

      120007128464

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efforts of International Institute for Integrative Sleep Medicine to solve sleep problems2018

    • Author(s)
      Shoji Fukusumi, Yo Oishi, Shingo Soya, Liqin Cao
    • Journal Title

      Bioscience & Industry

      Volume: 76(6) Pages: 516-521

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 睡眠の制御メカニズムとその破綻に伴う行動異常2018

    • Author(s)
      大石陽、林悠、柳沢正史
    • Journal Title

      実験医学増刊

      Volume: 36(12) Pages: 81-87

    • Related Report
      2018 Annual Research Report
  • [Presentation] DREADD-mediated slow-wave generation in mice2022

    • Author(s)
      Yo Oishi
    • Organizer
      WPI-IIIS/Fudan University Joint Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Sleep-wake regulation by reward systems2018

    • Author(s)
      Yo Oishi
    • Organizer
      The 43rd Annual Meeting of Japanese Society of Sleep Research
    • Related Report
      2018 Annual Research Report
  • [Presentation] Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice2018

    • Author(s)
      Yo Oishi
    • Organizer
      The 43rd Annual Meeting of Japanese Society of Sleep Research
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] Adenosinergic control of sleep. In: Principles and Practice of Sleep Medicine (Seventh Edition)2020

    • Author(s)
      Lazarus M, Oishi Y, Landolt HP
    • Publisher
      Elsevier
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-12-28  

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