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Developing a method for differential genetic manipulations on two types of neurons within a local neural circuit of the central circadian clock

Research Project

Project/Area Number 18K19421
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionKanazawa University

Principal Investigator

MIEDA Michihiro  金沢大学, 医学系, 教授 (20296552)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsサーカディアンリズム / 体内時計 / 視交叉上核 / 神経ネットワーク / 遺伝子操作マウス / アデノ随伴ウイルスベクター / 光遺伝学 / カルシウムセンサー / 局所神経ネットワーク / カルシウム / 局所神経回路網 / トランスジェニックマウス / ゲノム編集
Outline of Final Research Achievements

Using the neural network of the central circadian clock of the suprachiasmatic nucleus (SCN) as a model, we aimed to construct a strategy for analyzing intercellular communications between different two types of neurons within a complex local circuit, by differential genetic and optogenetic manipulations on those different neuronal types. Its specific purposes include recording responses of one neuron type to the stimulation of another neuron type, recording activities of two types of neurons simultaneously, and uncovering upstream/downstream relationships between two types of neurons. To do this, we generated novel genetically-modified mouse lines and recombinant adeno-associated viral vectors. We also set up a system to record the neuronal activity of a particular type of neurons in vivo. Thus, we have successfully constructed such a strategy.

Academic Significance and Societal Importance of the Research Achievements

中枢概日時計・視交叉上核神経ネットワークは、多種・多数の神経細胞間のコミュニケーションを介し、強固で安定な概日振動を発振する。しかしながら、視交叉上核の神経回路レベルでの動作原理に関する知見は驚くほど少ない。本研究は中枢概日時計神経ネットワークの動作原理解明において、これまでに無い斬新なアプローチを採るもので、学術的意義が大きい。加えて、神経科学・神経生理学全般に対し、複雑な局所神経回路網の機能を解析する上での、新たな方法論を提供する。また、概日時計の変調や他の局所神経回路の異常に起因する健康障害・疾患の病態生理の理解、さらにはその対処法の開発に繋がれば、社会的意義も大きい。

Report

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

    (19 results)

All 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] The central circadian clock of the suprachiasmatic nucleus as an ensemble of multiple oscillatory neurons.2020

    • Author(s)
      Mieda M.
    • Journal Title

      Neurosci Res

      Volume: in press Pages: 24-31

    • DOI

      10.1016/j.neures.2019.08.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 概日時計と睡眠2020

    • Author(s)
      三枝理博
    • Journal Title

      生体の科学

      Volume: 71 Pages: 18-22

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Dopamine D2L Receptor Deficiency Causes Stress Vulnerability through 5-HT1A Receptor Dysfunction in Serotonergic Neurons2019

    • Author(s)
      Shioda Norifumi、Imai Yoshiki、Yabuki Yasushi、Sugimoto Wataru、Yamaguchi Kouya、Wang Yanyan、Hikida Takatoshi、Sasaoka Toshikuni、Mieda Michihiro、Fukunaga Kohji
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 38 Pages: 7551-7563

    • DOI

      10.1523/jneurosci.0079-19.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] レム睡眠発現制御・情動脱力発作とナルコレプシー2019

    • Author(s)
      三枝理博
    • Journal Title

      睡眠医療

      Volume: 13 Pages: 367-373

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Sexually Dimorphic Vasopressin Cells Modulate Social Investigation and Communication in Sex-Specific Ways.2019

    • Author(s)
      Rigney N, Whylings J, Mieda M, de Vries G, Petrulis A
    • Journal Title

      eNeuro

      Volume: 6 Issue: 1 Pages: ENEURO.0415-18.2019

    • DOI

      10.1523/eneuro.0415-18.2019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice2019

    • Author(s)
      Zhang Tong、Yanagida Junko、Kamii Hironori、Wada Shintaro、Domoto Masaki、Sasase Hitoki、Deyama Satoshi、Takarada Takeshi、Hinoi Eiichi、Sakimura Kenji、Yamanaka Akihiro、Maejima Takashi、Mieda Michihiro、Sakurai Takeshi、Nishitani Naoya、Nagayasu Kazuki、Kaneko Shuji、Minami Masabumi、Kaneda Katsuyuki
    • Journal Title

      Addiction Biology

      Volume: 印刷中 Issue: 1 Pages: 1-11

    • DOI

      10.1111/adb.12723

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Network Mechanism of the Central Circadian Pacemaker of the SCN: Do AVP Neurons Play a More Critical Role Than Expected?2019

    • Author(s)
      Mieda M.
    • Journal Title

      Front Neurosci

      Volume: 13 Pages: 139-139

    • DOI

      10.3389/fnins.2019.00139

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons2018

    • Author(s)
      Saito Yuki C.、Maejima Takashi、Nishitani Mitsuhiro、Hasegawa Emi、Yanagawa Yuchio、Mieda Michihiro、Sakurai Takeshi
    • Journal Title

      The Journal of Neuroscience

      Volume: 38 Issue: 28 Pages: 6366-6378

    • DOI

      10.1523/jneurosci.2835-17.2018

    • NAID

      120007133906

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats.2018

    • Author(s)
      Fujiwara T, Nakata R, Ono M, Mieda M, Ando H, Daikoku T, Fujiwara H.
    • Journal Title

      Curr Dev Nutr

      Volume: 3 Issue: 4 Pages: 1-7

    • DOI

      10.1093/cdn/nzy093

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] AVPニューロン特異的小胞GABAトランスポーターノックアウトマウスにおける視交叉上核概日リズムのインビボ解析2020

    • Author(s)
      津野祐輔、前島隆司、長谷川恵美、三枝理博
    • Organizer
      第97回日本生理学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 中枢概日時計神経ネットワークの遺伝学的解析2019

    • Author(s)
      三枝理博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] AVPニューロン特異的Vgatノックアウトマウスにおける視交叉上核概日リズムのインビトロ、行動、及びインビボ解析2019

    • Author(s)
      津野祐輔、前島隆司、長谷川恵美、三枝理博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GABAergic transmission of AVP neurons regulates correctly timed output of the central circadian pacemaker of the SCN.2019

    • Author(s)
      三枝理博、長谷川恵美、津野祐輔、前島隆司
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳類中枢概日時計の神経メカニズム2019

    • Author(s)
      三枝理博
    • Organizer
      明治大学現象数理学共同研究集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Analysis of the central circadian clock in AVP neuron-specific VGAT deficient mice2019

    • Author(s)
      "前島隆司 長谷川恵美 津野祐輔 三枝理博"
    • Organizer
      第9回アジア・オセアニア生理学会連合(FAOPS)2019年大会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中枢概日時計におけるバソプレシンニューロンの機能2018

    • Author(s)
      三枝理博
    • Organizer
      第43回日本睡眠学会定期学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Genetic dissection of neural mechanisms underlying the central circadian pacemaker2018

    • Author(s)
      三枝理博
    • Organizer
      Sapporo Symposium on Biological Rhythm in 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural mechanisms underlying the central circadian pacemaker of the SCN2018

    • Author(s)
      三枝理博
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] AVP神経特異的小胞GABAトランスポーター遺伝子欠損マウスにおける中枢概日時計の解析2018

    • Author(s)
      AVP神経特異的小胞GABAトランスポーター遺伝子欠損マウスにおける中枢概日時計の解析
    • Organizer
      第25回日本時間生物学会学術大会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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