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Elucidation of the function of the sleep architecture based on the identification of novel brainstem neuronal circuits

Research Project

Project/Area Number 20H03353
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionThe University of Tokyo (2022)
Kyoto University (2020-2021)

Principal Investigator

HAYASHI Yu  東京大学, 大学院理学系研究科(理学部), 教授 (40525812)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords睡眠 / マウス / 脳幹 / 神経回路 / 化学遺伝学
Outline of Research at the Start

様々な疾患や発達障害において、睡眠構築(レム睡眠やノンレム睡眠や中途覚醒が一晩の間に現れるパターン)の異常が長期にわたって続く。こうした異常が脳機能に及ぼす影響はよくわかっていない。私たちはこれまでに、睡眠構築制御を司る脳幹の神経ネットワークの解明を進めてきた。その過程で、レム睡眠やノンレム睡眠を一過的または長期的に操作できるマウスを構築した。本研究では、こうした私たち独自の睡眠構築制御技術を活用し、正常な睡眠構築が脳機能に果たす役割を解明する。その際、分子レベルから神経回路レベル・行動レベルまで解析を行い、睡眠構築の重要性を解明するとともに、睡眠構築を生み出す神経回路の動作原理も解明する。

Outline of Final Research Achievements

In this study, we have been working to elucidate the effects of intervening the sleep architecture for long periods on brain functions and their molecular mechanisms in mice. To this end, we chronically manipulated the neural circuits that control sleep architecture. As a result, we found that mice in which sleep architecture was manipulated show various behavioral abnormalities and that there are abnormalities in gene expression in the cerebral cortex and hippocampus. In addition, as a result of further clarification of the operating principles of neurons that control sleep architecture, several groups of neurons that control REM and non-REM sleep have been identified, revealing part of the neural basis for the various effects of interventions on sleep architecture.

Academic Significance and Societal Importance of the Research Achievements

睡眠構築は、疾患や発達障害、さらには睡眠薬の影響を大きく受ける。こうした長期的な睡眠構築の異常がもたらす影響についてはよくわかっていない。ヒトでの前向きな調査研究では、睡眠構築の特徴によっては、認知症を発症するリスクや様々な要因で死亡するリスクが高まることが近年報告されたが、因果関係は明らかでない。本研究で私たちはマウスにおいて、最新の神経科学ツールを用いて睡眠構築に介入することで、様々な影響が生じることを見出した。これらの知見は、一部の動物で複雑に進化した睡眠構築という謎多い生理現象の意義を理解する重要な手掛かりを与えるものと期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (21 results)

All 2023 2022 2021 2020 Other

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 9 results) Presentation (4 results) (of which Invited: 4 results) Remarks (3 results)

  • [Journal Article] ER proteostasis regulators cell-non-autonomously control sleep2023

    • Author(s)
      Kawano Taizo、Kashiwagi Mitsuaki、Kanuka Mika、Chen Chung-Kuan、Yasugaki Shinnosuke、Hatori Sena、Miyazaki Shinichi、Tanaka Kaeko、Fujita Hidetoshi、Nakajima Toshiro、Yanagisawa Masashi、Nakagawa Yoshimi、Hayashi Yu
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 3 Pages: 112267-112267

    • DOI

      10.1016/j.celrep.2023.112267

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bidirectional relationship between sleep and depression2023

    • Author(s)
      Yasugaki Shinnosuke、Okamura Hibiki、Kaneko Ami、Hayashi Yu
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 57-64

    • DOI

      10.1016/j.neures.2023.04.006

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] レム睡眠中の大脳血流量の大幅な上昇の直接的な証拠――睡眠中の脳のリフレッシュ機構の解明に向けて2022

    • Author(s)
      蔡佳容, 菅沼 貴也, 林 悠
    • Journal Title

      医学のあゆみ(医歯薬出版株式会社)

      Volume: 281 Pages: 776-777

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors2021

    • Author(s)
      Tsai Chia-Jung、Nagata Takeshi、Liu Chih-Yao、Suganuma Takaya、Kanda Takeshi、Miyazaki Takehiro、Liu Kai、Saitoh Tsuyoshi、Nagase Hiroshi、Lazarus Michael、Vogt Kaspar E.、Yanagisawa Masashi、Hayashi Yu
    • Journal Title

      Cell Reports

      Volume: 36 Issue: 7 Pages: 109558-109558

    • DOI

      10.1016/j.celrep.2021.109558

    • NAID

      120007141681

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impaired wakefulness and rapid eye movement sleep in dopamine-deficient mice2021

    • Author(s)
      Kashiwagi Mitsuaki、Kanuka Mika、Tanaka Kaeko、Fujita Masayo、Nakai Ayaka、Tatsuzawa Chika、Kobayashi Kazuto、Ikeda Kazutaka、Hayashi Yu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 170-170

    • DOI

      10.1186/s13041-021-00879-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β2020

    • Author(s)
      Nakai Ayaka、Fujiyama Tomoyuki、Nagata Nanae、Kashiwagi Mitsuaki、Ikkyu Aya、Takagi Marina、Tatsuzawa Chika、Tanaka Kaeko、Kakizaki Miyo、Kanuka Mika、Kawano Taizo、Mizuno Seiya、Sugiyama Fumihiro、Takahashi Satoru、Funato Hiromasa、Sakurai Takeshi、Yanagisawa Masashi、Hayashi Yu
    • Journal Title

      Genetics

      Volume: 216 Issue: 3 Pages: 753-764

    • DOI

      10.1534/genetics.120.303435

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolutionary Origin of Distinct NREM and REM Sleep2020

    • Author(s)
      Yamazaki Risa、Toda Hirofumi、Libourel Paul-Antoine、Hayashi Yu、Vogt Kaspar E.、Sakurai Takeshi
    • Journal Title

      Frontiers in Psychology

      Volume: 11 Pages: 1-8

    • DOI

      10.3389/fpsyg.2020.567618

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: The Gating and Maintenance of Sleep and Wake: New Circuits and Insights2020

    • Author(s)
      Lazarus Michael、Hayashi Yu、Honjoh Sakiko、Vogt Kaspar E.、Eban-Rothschild Ada、Liu Qinghua、Sakurai Takeshi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 1-3

    • DOI

      10.3389/fnins.2020.00773

    • NAID

      120007165426

    • Related Report
      2020 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Multimodal nonlinear optical imaging ofCaenorhabditis eleganswith multiplex coherent anti-Stokes Raman scattering, third-harmonic generation, second-harmonic generation, and two-photon excitation fluorescence2020

    • Author(s)
      Miyazaki Shinichi、Leproux Philippe、Couderc Vincent、Hayashi Yu、Kano Hideaki
    • Journal Title

      Applied Physics Express

      Volume: 13 Issue: 7 Pages: 072002-072002

    • DOI

      10.35848/1882-0786/ab9711

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The existence of two states of sleep as a common trait in various animals and its molecular and neuronal mechanisms2020

    • Author(s)
      Kashiwagi Mitsuaki、Hayashi Yu
    • Journal Title

      Current Opinion in Physiology

      Volume: 15 Pages: 197-202

    • DOI

      10.1016/j.cophys.2020.03.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Copine-7 Is Required for REM Sleep Regulation Following Cage Change or Water Immersion and Restraint Stress in Mice2020

    • Author(s)
      Chih-Yao Liu, Chia-Jung Tsai, Shinnosuke Yasugaki, Nanae Nagata, Miho Morita, Ayako Isotani, Masashi Yanagisawa, and Yu Hayashi.
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 14-25

    • DOI

      10.1016/j.neures.2020.04.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progressive Changes in Sleep and Its Relations to Amyloid-β Distribution and Learning in Single App Knock-In Mice2020

    • Author(s)
      Maezono Sakura Eri B.、Kanuka Mika、Tatsuzawa Chika、Morita Miho、Kawano Taizo、Kashiwagi Mitsuaki、Nondhalee Pimpimon、Sakaguchi Masanori、Saito Takashi、Saido Takaomi C.、Hayashi Yu
    • Journal Title

      eneuro

      Volume: 7 Issue: 2 Pages: 1-14

    • DOI

      10.1523/eneuro.0093-20.2020

    • NAID

      120007163363

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep architecture of adenosine A2A receptor-deficient mice2020

    • Author(s)
      Tsai Chia-Jung, Liu Chih-Yao, Lazarus Michael, Hayashi Yu
    • Journal Title

      Sleep and Biological Rhythms

      Volume: - Issue: 3 Pages: 275-279

    • DOI

      10.1007/s41105-020-00260-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Widely Distributed Neurotensinergic Neurons in the Brainstem Regulate NREM Sleep in Mice.2020

    • Author(s)
      Kashiwagi M, Kanuka M, Tatsuzawa C, Suzuki H, Morita M, Tanaka K, Kawano T, Shin JW, Suzuki H, Itohara S, Yanagisawa M, Hayashi Y.
    • Journal Title

      Curr Biol.

      Volume: 30 Issue: 6 Pages: 1002-1010

    • DOI

      10.1016/j.cub.2020.01.047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Genetic and imaging approaches to elucidate the roles of REM sleep2020

    • Author(s)
      林 悠
    • Organizer
      記憶研究会2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 睡眠に注目した新規な脳恒常性維持機構の解明2020

    • Author(s)
      林 悠
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] レム睡眠の意義とメカニズム~マウスの遺伝学・イメージングからのアプローチ~2020

    • Author(s)
      林 悠
    • Organizer
      第71回 日本薬理学会北部会次世代薬理学セミナー2020 in 仙台
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Crucial roles for REM sleep in maintaining brain homeostasis as revealed from genetic and imaging approaches2020

    • Author(s)
      林 悠
    • Organizer
      第43回 日本神経科学大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 生理学研究室

    • URL

      https://www.med.kyoto-u.ac.jp/organization-staff/research/human_health/ot0101/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 京都大学教育研究活動データベース

    • URL

      https://kyouindb.iimc.kyoto-u.ac.jp/j/xS3wT

    • Related Report
      2020 Annual Research Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/h-z-k

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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