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Chemogenetic dissection of the primate prefronto-subcortical pathways

Research Project

Project/Area Number 21K07268
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51020:Cognitive and brain science-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Oyama Kei  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 主任研究員 (50615250)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords霊長類 / 化学遺伝学 / 高次脳機能 / 前頭前野 / 視床 / 線条体 / 前頭連合野
Outline of Research at the Start

ヒトを含む霊長類の様々な高次脳機能の実現において前頭連合野の関与は必須であるが、前頭連合野から密な投射を受け取る線条体や視床MD核などの皮質下領域もまた、重要な役割を果たしている。しかし、これらの領域を結ぶ神経経路がどのような情報を伝達し、様々な高次脳機能が実現されているかについてはいまだ不明である。本研究課題では、化学遺伝学的手法を用いた霊長類脳における特定神経経路の機能阻害法により、霊長類前頭連合野と線条体・視床MD核を結ぶ神経経路が、高次脳機能の実現において、それぞれどのような役割を果たしているのかを、行動・局所回路・広域ネットワークのレベルで解き明かすことを目指す。

Outline of Final Research Achievements

In this study, we investigated the role of neural pathways linking prefrontal and subcortical regions in higher brain functions, i.e., which higher brain functions are affected by inhibition of specific pathway functions, and which information processing in downstream regions and in the wider network? To answer the question we conducted behavioral experiments to clarify the role of two primate neural pathways, the dorsolateral prefrontal - striatum and the dorsolateral prefrontal - thalamic MD nucleus, in the implementation of higher brain functions at the level of behaviour, local circuits and wide-area networks. The results showed that the neural pathways connecting the prefrontal - striatum and the prefrontal - thalamic MD nucleus have different functional roles.

Academic Significance and Societal Importance of the Research Achievements

本研究で対象としている①前頭前野―線条体経路は注意欠陥・多動性障害(ADHD)や強迫性障害(OCD)など、②前頭前野―視床MD核経路は統合失調症などの精神疾患患者の脳において、しばしば機能的結合の異常が認められることが報告されており、その活動の適正化がこれらの疾患の治療につながることが期待される。また、本研究課題で開発した特定神経路機能操作法は様々な領域間で適用可能である高い汎用性を有しており、神経経路の機能異常を原因とする幅広い疾患の神経基盤の理解へとつながることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

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

  • [Journal Article] Targeted Delivery of Chemogenetic Adeno-Associated Viral Vectors to Cortical Sulcus Regions in Macaque Monkeys by Handheld Injections2023

    • Author(s)
      Oyama Kei、Nagai Yuji、Minamimoto Takafumi
    • Journal Title

      BIO-PROTOCOL

      Volume: 13 Issue: 23

    • DOI

      10.21769/bioprotoc.4897

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multimodal imaging for validation and optimization of ion channel-based chemogenetics in nonhuman primates2023

    • Author(s)
      Yuki Hori, Yuji Nagai, Yukiko Hori, Kei Oyama, Koki Mimura, Toshiyuki Hirabayashi, Ken-ichi Inoue, Masayuki Fujinaga, Ming-Rong Zhang, Masahiko Takada, Makoto Higuchi, Takafumi Minamimoto
    • Journal Title

      Journal of Neuroscience

      Volume: 43 Issue: 39 Pages: 6619-6627

    • DOI

      10.1523/jneurosci.0625-23.2023

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenetic attenuation of cortical seizures in nonhuman primates2023

    • Author(s)
      Miyakawa Naohisa、Nagai Yuji、Hori Yukiko、Mimura Koki、Orihara Asumi、Oyama Kei、Matsuo Takeshi、Inoue Ken-ichi、Suzuki Takafumi、Hirabayashi Toshiyuki、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Kawasaki Keisuke、Minamimoto Takafumi
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41467-023-36642-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenetic Disconnection between the Orbitofrontal Cortex and the Rostromedial Caudate Nucleus Disrupts Motivational Control of Goal-Directed Action2022

    • Author(s)
      Oyama Kei、Hori Yukiko、Mimura Koki、Nagai Yuji、Eldridge Mark A. G.、Saunders Richard C.、Miyakawa Naohisa、Hirabayashi Toshiyuki、Hori Yuki、Inoue Ken-ichi、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Richmond Barry J.、Minamimoto Takafumi
    • Journal Title

      The Journal of Neuroscience

      Volume: 42 Issue: 32 Pages: 6267-6275

    • DOI

      10.1523/jneurosci.0229-22.2022

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making2021

    • Author(s)
      Oyama Kei、Hori Yukiko、Nagai Yuji、Miyakawa Naohisa、Mimura Koki、Hirabayashi Toshiyuki、Inoue Ken-ichi、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Minamimoto Takafumi
    • Journal Title

      Science Advances

      Volume: 7 Issue: 26 Pages: 1-9

    • DOI

      10.1126/sciadv.abg4246

    • NAID

      120007089253

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Distinct roles of pathways from monkey orbitofrontal cortex to caudate nucleus and mediodorsal thalamus in value-based adaptive decision-making2022

    • Author(s)
      小山 佳
    • Organizer
      第45回日本神経科学大会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chemogenetic dissection of the primate prefronto-subcortical pathways for higher-order functions2021

    • Author(s)
      小山 佳
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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