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Interrogation of the spatiotemporal integration of dopaminergic signaling in striatal medium spiny neurons

Research Project

Project/Area Number 20H03349
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 InstitutionNiigata University

Principal Investigator

Uchigashima Motokazu  新潟大学, 脳研究所, 准教授 (10614662)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywordsドーパミン / 線条体 / グルタミン酸 / スパイン / ゲノム編集 / 分子標識 / 中型有棘ニューロン / 遺伝子組み換え / イメージング / シナプス
Outline of Research at the Start

動物やヒトはどのような感覚情報や行動が報酬に結びつくのかを学習する(報酬学習)。 線条体ニューロンは感覚・運動情報をコードした大脳皮質からのグルタミン酸入力と報酬情報をコードした中脳からのドーパミン入力を受けるため、両者のシグナル統合が報酬学習の細胞基盤と想定されている。しかし、この統合が時空間的にどのように行われているのかは十分わかっていない。本研究は、ドーパミン伝達を可視化・操作する技術の開発を通じて、ドーパミンとグルタミン酸の細胞内シグナル統合過程の時空間選択性の理解を目指す。

Outline of Final Research Achievements

Dopaminergic transmission is essential for our normal brain function, and its dysfunction causes many brain disorders such as Parkinson's disease and schizophrenia. However, our current knowledge is not sufficient about where dopamine is released from and what it targets to, and how it functions on its target cells. To address these questions, we newly developed a genome editing-based platform to visualize molecularly-defined dopamine release sites and simultaneously introduce Cre recombinase for neuronal labeling or manipulation in the same neurons in mammalian brains.

Academic Significance and Societal Importance of the Research Achievements

本研究にて確立した新たな技術は、中脳ドーパミンニューロンへの応用を通じて、これまで不十分であった脳組織中におけるドーパミン伝達の多元的かつ高精度な理解が可能となる。この結果、正常な脳の機能する仕組みの理解が深まるだけでなく、多数の罹患者が存在する多様な脳機能疾患におけるドーパミン伝達異常の高精度な理解が可能となることで、そこから生み出される新たな治療アプローチの創出にも結びつくと期待できる。

Report

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

    (14 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (5 results) (of which Invited: 1 results)

  • [Int'l Joint Research] マサチューセッツ州立大学医学部(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] マサチューセッツ州立大学医学部(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] マサチューセッツ大学医学部(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process2022

    • Author(s)
      Hanaoka Kenjiro、Iwaki Shimpei、Yagi Kiyoshi、Myochin Takuya、Ikeno Takayuki、Ohno Hisashi、Sasaki Eita、Komatsu Toru、Ueno Tasuku、Uchigashima Motokazu、Mikuni Takayasu、Tainaka Kazuki、Tahara Shinya、Takeuchi Satoshi、Tahara Tahei、Uchiyama Masanobu、Nagano Tetsuo、Urano Yasuteru
    • Journal Title

      Journal of the American Chemical Society

      Volume: 144 Issue: 43 Pages: 19778-19790

    • DOI

      10.1021/jacs.2c06397

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction2021

    • Author(s)
      Uchigashima Motokazu、Cheung Amy、Futai Kensuke
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 14 Pages: 749164-749164

    • DOI

      10.3389/fnmol.2021.749164

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Specific Neuroligin3?αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus2020

    • Author(s)
      Uchigashima Motokazu、Konno Kohtarou、Demchak Emily、Cheung Amy、Watanabe Takuya、Keener David G、Abe Manabu、Le Timmy、Sakimura Kenji、Sasaoka Toshikuni、Uemura Takeshi、Imamura Kawasawa Yuka、Watanabe Masahiko、Futai Kensuke
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.59545

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons2020

    • Author(s)
      Fukabori R, Iguchi Y, Kato S, Takahashi K, Eifuku S, Tsuji S, Hazama A, Uchigashima M, Watanabe M, Mizuma H, Cui Y, Onoe H, Hikishima K, Yasoshima Y, Osanai M, Inagaki R, Fukunaga K, Nishijo T, Momiyama T, Benton R, & Kobayashi K
    • Journal Title

      The Journal of Neuroscience

      Volume: 40 Issue: 43 Pages: 8367-8385

    • DOI

      10.1523/jneurosci.1720-20.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus2020

    • Author(s)
      Uchigashima Motokazu、Leung Ming、Watanabe Takuya、Cheung Amy、Le Timmy、Pallat Sabine、Dinis Alexandre Luis Marques、Watanabe Masahiko、Kawasawa Yuka Imamura、Futai Kensuke
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 25 Pages: 8589-8595

    • DOI

      10.1074/jbc.ac120.012571

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methodological approaches to understand the molecular mechanism of structural plasticity of dendritic spines2020

    • Author(s)
      Mikuni Takayasu、Uchigashima Motokazu
    • Journal Title

      European Journal of Neuroscience

      Volume: in press Issue: 8 Pages: 6902-6911

    • DOI

      10.1111/ejn.14734

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Development of Single-Cell, Spatiotemporal, Quantitative Imaging Method for Endogenous Proteins in Mammalian Brains2023

    • Author(s)
      Motokazu Uchigashima, Risa Iguchi, Kazuma Fujii, Pratik Kumar, Manabu Abe, Motohiro Nozumi, Michihiro Igarashi, Kenji Sakimura, Ryoma Bise, Luke D Lavis, and Takayasu Mikuni
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Quantitative, Spatiotemporal Profiling of Endogenous Proteins in Mammalian Brain Tissues via CRISPR/Cas9-Based Knock-in of Chemical Tags2022

    • Author(s)
      Motokazu Uchigashima, Risa Iguchi, Xinyi Liu, Kazuma Fujii, Manabu Abe, Kenji Sakimura, Ryoma Bise, Takayasu Mikuni
    • Organizer
      NEURO2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] SeeThrough - live neuronal imaging through cleared skull in mammalian brain2022

    • Author(s)
      Xinyi Liu, Motokazu Uchigashima, Manabu Abe, Kenji Sakimura, Kazuki Tainaka, Takayasu Mikuni
    • Organizer
      第11回 生理研‐霊長研‐脳研 合同シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] シナプス構成タンパク質をハイスループットに可視化するための技術開発2021

    • Author(s)
      内ヶ島基政
    • Organizer
      第759回新潟医学会例会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Specific Neuroligin3-αNeurexin1 Trans-synaptic Interaction Regulates GABAergic Synaptic Function in an Input Cell Type-Dependent Manner2021

    • Author(s)
      Uchigashima Motokazu、Konno Kohtarou、Demchak Emily、Cheung Amy、Watanabe Takuya、Keener David G、Abe Manabu、Le Timmy、Sakimura Kenji、Sasaoka Toshikuni、Uemura Takeshi、Imamura Kawasawa Yuka、Watanabe Masahiko、Futai Kensuke
    • Organizer
      第126回 日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report

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

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