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Signal transduction and motor control regulated through by direct and indirect pathways in the basal ganglia to the thalamus

Research Project

Project/Area Number 21K07257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionFujita Health University (2022-2023)
National Institute for Physiological Sciences (2021)

Principal Investigator

Sano Hiromi  藤田医科大学, 精神・神経病態解明センター, 准教授 (00363755)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords大脳基底核 / 線条体 / 黒質網様部 / 視床 / パーキンソン病 / 随意運動
Outline of Research at the Start

大脳基底核の直接路と間接路を介する神経伝達がどのように視床へ伝わり運動を制御しているのかを解明するため、以下のことを明らかにする。
(1)光遺伝学を用いた直接路あるいは間接路の興奮により、視床の神経活動がどのように変化するのかをマウス個体から記録する。
(2)パーキンソン病モデル動物において直接路あるいは間接路の興奮を誘導し、視床の神経活動を記録する。
(3)光遺伝学を用いて視床ニューロンを興奮あるいは抑制させたとき、直接路や間接路の作用と同じように、運動の開始や促進、あるいは終了や抑制が引き起こされるのかどうかを検証する。

Outline of Final Research Achievements

The basal ganglia (BG) are supposed to control voluntary movements.The BG receive input from the cortex, and process the information through pathways called direct, indirect, and hyperdirect pathways, and send the information back to the cortex through the thalamus. To clarify how the direct and indirect pathways regulate the activity in the substantia nigra pars reticulata (SNr), where is the output nuclei of the BG, and the thalamus, we used optogenetics to induce selective excitation in the direct or indirect pathways and recorded neuronal activity in the SNr and thalamus.
In the SNr, the direct pathway induced inhibition, and the collateral of the direct pathway induced excitation. The indirect pathway induced excitation in the SNr and inhibition in the thalamus. These changes in activity will contribute to motor control.

Academic Significance and Societal Importance of the Research Achievements

直接路と間接路の神経生理学的な役割の解明は、大脳基底核が制御する正常な随意運動のメカニズムを解明するうえで不可欠であり、随意運動の精密な制御に関して基本的な知見を提供し、脳内の情報処理メカニズム、ネットワークダイナミクスに対する理解が深まる。また、大脳基底核の機能異常に起因するパーキンソン病やハンチントン舞踏病の病態生理学的変化を解明するための、重要な手がかりを提供することもできる。大脳基底核の機能に関する理解が深まることで、運動障害に対する新たな治療法の開発が期待できる。

Report

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

    (18 results)

All 2024 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results)

  • [Journal Article] Behavioral effects of zonisamide on L-DOPA-induced dyskinesia in Parkinson's disease model mice2023

    • Author(s)
      Sano Hiromi、Nambu Atsushi
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 15 Pages: 1221341-1221341

    • DOI

      10.3389/fnagi.2023.1221341

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shared GABA transmission pathology in dopamine agonist- and antagonist-induced dyskinesia2023

    • Author(s)
      Abe Yoshifumi、Yagishita Sho、Sano Hiromi、Sugiura Yuki、Dantsuji Masanori、Suzuki Toru、Mochizuki Ayako、Yoshimaru Daisuke、Hata Junichi、Matsumoto Mami、Taira Shu、Takeuchi Hiroyoshi、Okano Hideyuki、Ohno Nobuhiko、Suematsu Makoto、Inoue Tomio、Nambu Atsushi、Watanabe Masahiko、Tanaka Kenji F.
    • Journal Title

      Cell Reports Medicine

      Volume: 4 Issue: 10 Pages: 101208-101208

    • DOI

      10.1016/j.xcrm.2023.101208

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic Activity Model of Movement Disorders: The Fundamental Role of the Hyperdirect Pathway2023

    • Author(s)
      Nambu Atsushi、Chiken Satomi、Sano Hiromi、Hatanaka Nobuhiko、Obeso Jose A.
    • Journal Title

      Movement Disorders

      Volume: 38 Issue: 12 Pages: 2145-2150

    • DOI

      10.1002/mds.29646

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dopamine drives neuronal excitability via KCNQ channel phosphorylation for reward behavior2022

    • Author(s)
      Tsuboi Daisuke、Otsuka Takeshi、Shimomura Takushi、Faruk Md Omar、Yamahashi Yukie、Amano Mutsuki、Funahashi Yasuhiro、Kuroda Keisuke、Nishioka Tomoki、Kobayashi Kenta、Sano Hiromi、Nagai Taku、Yamada Kiyofumi、Tzingounis Anastasios V.、Nambu Atsushi、Kubo Yoshihiro、Kawaguchi Yasuo、Kaibuchi Kozo
    • Journal Title

      Cell Reports

      Volume: 40 Issue: 10 Pages: 111309-111309

    • DOI

      10.1016/j.celrep.2022.111309

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Pathophysiological changes in a mouse model of Parkinson's disease and novel therapeutic approach through acctivation of the PKA/Rap1 cascade2024

    • Author(s)
      Hiromi Sano
    • Organizer
      International Symposium on Brain Structure and Function
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cortico-basal ganglia neural circuit dynamics in mouse models of drug-induced dyskinesia2024

    • Author(s)
      Hiromi Sano, Kenta Kobayashi, Satomi Chiken, Atsushi Nambu, Kozo Kaibuchi
    • Organizer
      第47回日本神経科学大会/第46回日本生物学的精神医学会年会/第67回日本神経化学会大会/第8回アジアオセアニア神経科学連合コングレス
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Dystonia musculorumマウスが示す運動異常における感覚運動回路の役割2023

    • Author(s)
      吉岡望、黒瀬雅之、佐野裕美、知見聡美、山村健介、南部篤、竹林浩秀
    • Organizer
      第64回日本神経病理学会総会学術研究会/第66回日本神経化学会大会合同大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] パーキンソン病モデルマウスの病態生理学的変化とPKA/Rap1カスケードの活性化によるその改善2023

    • Author(s)
      佐野裕美、小林憲太、知見聡美、南部篤、貝淵弘三
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病治療薬・方法の神経生理学的評価2023

    • Author(s)
      南部篤、知見聡美、佐野裕美
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 大脳皮質-大脳基底核ループの動作異常と不随意運動との関係2023

    • Author(s)
      佐野裕美
    • Organizer
      第53回日本神経精神薬理学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Activation of the PKA/Rap1 cascade ameliorates Psrkinsonian symptoms2023

    • Author(s)
      Hiromi Sano, Kenta Kobayashi, Kozo Kaibuchi
    • Organizer
      Fujita International Symposium on Brain Sceince 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gt(ROSA)26Sor-CAG-LF-AKT1ノックインマウス2系統(活性化型および野生型AKT)の樹立2023

    • Author(s)
      阪上起世、黒川理薫、宮地均、北野さつき、佐野裕美、小林憲太、小倉淳
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Activation of the PKA/Rap1 cascade ameliorates motor symptoms in a mouse model of Parkinson’s disease2023

    • Author(s)
      Sano H, Kobayashi K, Kaibuchi K
    • Organizer
      2022 NIPS research meeting ‘’Multi-disciplinary approach to understand neuronal network architecture to control motor actions’’
    • Related Report
      2022 Research-status Report
  • [Presentation] Pathophysiological changes in a mouse model of Parkinson’s disease and its amelioration through activation of the PKA/Rap1 cascade2023

    • Author(s)
      Sano H, Kobayashi K, Chiken S, Nambu A, Kaibuchi K
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Neurophysiological method to develop new therapies for Parkinson’s disease2023

    • Author(s)
      Nambu A, Chiken S, Sano H
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Pathophysiological changes of the basal ganglia in Parkinson’s disease and drug addiction2022

    • Author(s)
      Hiromi Sano
    • Organizer
      CIN-NIPS-Asia Pacific Systems Neuroscience Symposium 2022
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The effects of zonisamide, an anti-parkinsonian drug, on L-DOPA-induced dyskinesia in Parkinson’s disease model mice2022

    • Author(s)
      Hiromi Sano, Atsushi Nambu
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大脳基底核の回路変動と運動制御との関係2021

    • Author(s)
      佐野裕美
    • Organizer
      大阪大学タンパク質研究所セミナー
    • Related Report
      2021 Research-status Report
    • Invited

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

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