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Development of technologies for pathway-specific manipulation and application to disease models in primates

Research Project

Project/Area Number 21H02798
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionKyoto University

Principal Investigator

Yamaguchi Reona  京都大学, 高等研究院, 特定助教 (50812640)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords脊髄損傷 / サル / 機能回復 / ウイルスベクター / DREADD
Outline of Research at the Start

本研究では、ヒトに近い脳構造を持つマカクザルを対象とし、広範囲の脳領域に対して経路選択的かつ可逆的に操作ができる技術開発に取り組む。これを実現するために、広範囲にウイルスベクターを注入できるCED、特定の経路を選択できるウイルスベクター2重感染法、可逆的に経路を操作できるDREADDsという手法を組み合わせる。また、注入部位に脳波皮質電極を留置し、回路操作による脳活動の変化を明らかにする。さらに、当該回路操作技術をサル脊髄損傷モデルに適用し、脊髄損傷モデルからの機能回復に関わる脳機能を明らかにする。

Outline of Final Research Achievements

In this study, we developed a technique that can reversibly manipulate a wide range of neural circuits by combining CED for widespread virus vector injection, double viral vector technique for selecting specific pathways, and DREADDs for reversible pathway manipulation. Furthermore, we applied this circuit manipulation technique to a spinal cord injury model in a non-human primate. During the recovery process from spinal cord injury, blocking the interhemispheric pathway in the early stages of recovery resulted in a significant decrease in the success rate of the reach and grasp task. These results directly demonstrated the contribution of the interhemispheric pathway to functional recovery.

Academic Significance and Societal Importance of the Research Achievements

選択的回路操作の実験は、齧歯類を対象としたモデル動物で盛んに行われているが、霊長類を対象としたウイルスベクター注入実験の成功例は少ない。本研究課題で開発された技術は広汎な神経回路の操作を可能にするものであり、操作中の脳活動も記録することが可能である。このような技術は行動に影響を与える新規のネットワークの抽出に貢献でき、さらに病態モデルに応用することで、リハビリテーションの効果の評価や促進、新たな治療の創出への応用につながることも期待される。

Report

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

    (33 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (25 results) (of which Int'l Joint Research: 2 results) Book (3 results)

  • [Journal Article] How to study subjective experience in an animal model of blindsight?2024

    • Author(s)
      Yu Xiyao、Yamaguchi Reona、Isa Tadashi
    • Journal Title

      Neuroscience Research

      Volume: 201 Pages: 39-45

    • DOI

      10.1016/j.neures.2023.09.001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Balancing risk-return decisions by manipulating the mesofrontal circuits in primates2024

    • Author(s)
      Sasaki R., Ohta Y., Onoe H., Yamaguchi R., Miyamoto T., Tokuda T., Tamaki Y., Isa K., Takahashi J., Kobayashi K., Ohta J., Isa T.
    • Journal Title

      Science

      Volume: 383 Issue: 6678 Pages: 55-61

    • DOI

      10.1126/science.adj6645

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protocol for making an animal model of "blindsight" in macaque monkeys.2022

    • Author(s)
      Takakuwa N, Isa K, Yamaguchi R, Onoe H, Takahashi J, Yoshida M, Isa T
    • Journal Title

      STAR Protoc

      Volume: 4(1) Issue: 1 Pages: 101960-101960

    • DOI

      10.1016/j.xpro.2022.101960

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Micro-LED Array-Based Photo-Stimulation Devices for Optogenetics in Rat and Macaque Monkey Brains2021

    • Author(s)
      Ohta Yasumi、Guinto Mark Christian、Tokuda Takashi、Kawahara Mamiko、Haruta Makito、Takehara Hironari、Tashiro Hiroyuki、Sasagawa Kiyotaka、Onoe Hirotaka、Yamaguchi Reona、Koshimizu Yoshinori、Isa Kaoru、Isa Tadashi、Kobayashi Kenta、Akay Yasemin M.、Akay Metin、Ohta Jun
    • Journal Title

      IEEE Access

      Volume: 9 Pages: 127937-127949

    • DOI

      10.1109/access.2021.3111666

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-23 production in human macrophages is regulated negatively by tumor necrosis factor α-induced protein 3 and positively by specificity protein 1 after stimulation of the toll-like receptor 7/8 signaling pathway2021

    • Author(s)
      Rui Yamaguchi, Arisa Sakamoto, Reona Yamaguchi, Misa Haraguchi, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguch
    • Journal Title

      Heliyon

      Volume: 7 Issue: 2 Pages: e08887-e08887

    • DOI

      10.1016/j.heliyon.2022.e08887

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Supraspinal plasticity of the corticospinal projections after motor recovery from spinal cord injury in macaque monkeys2024

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Dexterous Finger Function Recovers Earlier In Spinal Cord Injury Monkeys Injected With The Synthetic Synaptic Organizing Protein CPTX2024

    • Author(s)
      Stefan Peyda, Reona Yamaguchi, Satoko Ueno, Kaoru Isa, Erika Omae, Kunimichi Suzuki, Veronica Chang, Hiroyuki Sasakura, Keiko Matsuda, Kenta Kobayashi, Kousei Takeuchi, Radu Aricescu, Hirotaka Onoe, Michisuke Yuzaki, Tadashi Isa
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] GLOBAL DISINHIBITION ASSOCIATED WITH RECOVERY OF HAND MOVEMENTS AFTER SPINAL CORD INJURY IN MONKEYS2023

    • Author(s)
      Reona Yamaguchi, Satoko Ueno, Toshinari Kawasaki, Zenas C. Chao, Masahiro Mitsuhashi, Kaoru Isa, Tomohiko Takei, K enta Kobayashi, Jun Takahashi, Hirotaka Onoe, Tadashi Isa
    • Organizer
      Benzon symposium no. 67
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] STATE-DEPENDENT ROLE OF INTERHEMISPHERIC PATHWAY FOR MOTOR RECOVERY IN PRIMATES2023

    • Author(s)
      Masahiro Mitsuhashi, Reona Yamaguchi, Toshinari Kawasaki, SatokoUeno, Kaoru Isa, Hirotaka Onoe, Tadashi Isa
    • Organizer
      Benzon symposium no. 67
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multi-hierarchical plasticity of the collaterals from corticospinal tract axons after spinal cord injury in the macaque monkeys2023

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      NEURO2023: The 46th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2023 Annual Research Report
  • [Presentation] Deep learning-based quantitative analysis for macaque hand dexterity2023

    • Author(s)
      Yiping Sun, Reona Yamaguchi, Tadashi Isa
    • Organizer
      第17回MotorControl研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Changes in cortical response to non-paretic hand stimulation in monkeys after spinal cord injury: a longitudinal fMRI study2022

    • Author(s)
      Takamichi Tohyama, Reona Yamaguchi, Naokazu Goda, Tetsuya Yamamoto, Kaoru Isa, Norihiro Sadoto, Tadashi Isa, Masaki Fukunaga
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] A Skull-Fit 8-channel phased-array Coil (SFiC) for high-resolution macaque MRI2022

    • Author(s)
      Shin-ichi Urayama, Tomohisa Okada, Reona Yamaguchi, Keigo Hikishima, Kei Kubota, Jun Takahashi, Yoshihiko Kawabata, Wim Vanduffel, Tadashi Isa, Hirotaka Onoe
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] Global disinhibition associated with recovery of hand movements after spinal cord injury2022

    • Author(s)
      Reona Yamaguchi, Toshinari Kawasaki, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Tadashi Isa
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] Optogenetical adjustment of the balance between risky and safer decision2022

    • Author(s)
      Ryo Sasaki, Yasumi Ohta, Hirotaka Onoe, Reona Yamaguchi, Takashi Tokuda, Kaoru Isa, Jun Takahashi, Kenta Kobayashi, Jun Ohta, Tadashi Isa
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] マカクザル皮質脊髄路損傷後の運動機能回復における大脳半球間連絡の役割2022

    • Author(s)
      三橋賢大, 山口玲欧奈, 川崎敏生, 上野里子, 高橋淳, 尾上浩隆,伊佐正
    • Organizer
      第 114 回近畿生理学談話
    • Related Report
      2022 Annual Research Report
  • [Presentation] リスク/リターンのバランスに基づく意思決定に関与する前頭皮質神経振動の解読2022

    • Author(s)
      宮本健史, 山口玲欧奈, 尾上浩隆, 伊佐正, 佐々木亮
    • Organizer
      第 114 回近畿生理学談話
    • Related Report
      2022 Annual Research Report
  • [Presentation] Brain activity in V1-lesioned Monkey2022

    • Author(s)
      Xiyao Yu, Reona Yamaguchi, Hakwan Lau, Tadashi Isa
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Contribution of the interhemispheric pathways to the recovery of dexterous hand movements after the corticospinal tract lesion in macaque monkeys2022

    • Author(s)
      Masahiro Mitsuhashi, Reona Yamaguchi, Toshinari Kawasaki, Satoko Ueno, Tadashi Isa
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] The corticospinal projections after the motor recovery from spinal cord injury in macaque monkeys2022

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Kawasaki Toshinari, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Deep learning-based quantitative analysis for macaque hand dexterity2022

    • Author(s)
      Yiping Sun, Reona Yamaguchi, Tadashi Isa
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Excitatory and inhibitory connectivities associated with global disinhibition promoting functional recovery from spinal cord injury2022

    • Author(s)
      Reona Yamaguchi, Yusuke Imoto, Tadashi Isa
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Decoding oscillatory power signals during risk-return decision-making in the prefrontal and premotor cortices.2022

    • Author(s)
      Takeshi Miyamoto, Reona Yamaguchi, Hirotaka Onoe, Tadashi Isa, Ryo Sasaki
    • Organizer
      The 100th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Global disinhibition associated with recovery of hand movements after spinal cord injury2021

    • Author(s)
      Reona Yamaguchi, Toshinari Kawasaki, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Tadashi Isa
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Massive re-routing of the corticospinal tract after spinal cord injury in the macaque monkeys2021

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Role of the interhemispheric pathways for the recovery of dexterous hand movements after the corticospinal tract lesion in macaque monkeys2021

    • Author(s)
      Masahiro Mitsuhashi, Reona Yamaguchi, Toshinari Kawasaki, Satoko Ueno, Tadashi Isa
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Activity of frontal network for performance of arm movement in a blindsight monkey2021

    • Author(s)
      Saya Kitazume, Yusuke Yamamoto, Reona Yamaguchi, Tadashi Isa
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脊髄損傷後における皮質脊髄路の大規模再構成2021

    • Author(s)
      上野里子、山口玲欧奈、伊佐かおる、川崎敏生、三橋賢大、伊佐正
    • Organizer
      第 113 回近畿生理学談話
    • Related Report
      2021 Annual Research Report
  • [Presentation] Global disinhibition associated with recovery of hand movements after spinal cord injury2021

    • Author(s)
      Reona Yamaguchi
    • Organizer
      The 99th Anniversary Annual Meeting of The Physiological Society of Japan
    • Related Report
      2021 Annual Research Report
  • [Presentation] Global disinhibition associated with recovery of hand movements after spinal cord injury2021

    • Author(s)
      Reona Yamaguchi
    • Organizer
      CIN-NIPS-Asia Pacific Systems Neuroscience Symposium 2022
    • Related Report
      2021 Annual Research Report
  • [Book] 霊長類学の百科事典 = The encyclopedia of primatology2023

    • Author(s)
      (分担執筆) 伊佐 正, 上野 里子, 山口 玲欧奈
    • Total Pages
      2
    • Publisher
      丸善出版
    • ISBN
      9784621308042
    • Related Report
      2023 Annual Research Report
  • [Book] 計測と制御2022

    • Author(s)
      山口 玲欧奈, 伊佐 正
    • Total Pages
      6
    • Publisher
      計測と制御
    • Related Report
      2022 Annual Research Report
  • [Book] 特集 運動制御の神経生理・機能解剖update-大脳,小脳,脊髄の連関 損傷脊髄の機能回復における運動野からの間接経路の関与2022

    • Author(s)
      伊佐 正, 三橋 賢大, 山口 玲欧奈
    • Total Pages
      7
    • Publisher
      脊椎脊髄ジャーナル
    • Related Report
      2022 Annual Research Report

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

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