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Relation between signal transduction, neuronal activities, and involuntary movements in neurodegeneration of the basal ganglia

Publicly Offered Research

Project AreaMechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
Project/Area Number 17H05590
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

佐野 裕美  生理学研究所, システム脳科学研究領域, 助教 (00363755)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywordsパーキンソン病 / 線条体 / 大脳基底核 / 随意運動 / 光遺伝学 / 神経科学 / 脳・神経 / 脳神経疾患 / 生理学 / ジスキネジア / 不随意運動
Outline of Annual Research Achievements

パーキンソン病は黒質のドパミン作動性ニューロンの脱落に起因する神経変性疾患で、重度な運動障害を示す。治療にはドパミンを補うように前駆体であるL-DOPAを投与することが有効であるが、長期間のL-DOPAの服用はジスキネジアと呼ばれる不随意運動を誘発してしまう。これまでの実験でマウスの線条体投射ニューロンを光遺伝学を用いて興奮誘導すると、パーキンソン病モデルマウスにおけるL-DOPA誘発性ジスキネジアと非常に類似した運動を誘発することを報告してきた。そこで、線条体投射ニューロンの興奮を誘導したときの神経活動を大脳基底核の出力核である黒質網様部から記録し、パーキンソン病モデルマウスにおけるL-DOPA誘発性ジスキネジアと比較した。一方で、L-DOPAでジスキネジアを誘発したパーキンソン病モデルマウスに対して、線条体投射ニューロンを光遺伝学を用いて抑制したときに、ジスキネジアがどのように変化するのかを観察した。
L-DOPA誘発性ジスキネジアを示すパーキンソン病モデルマウスにおいて、大脳皮質運動野を電気刺激したときに黒質網様部で一過性の「早い興奮-抑制-遅い興奮」という三相性の応答が認められた。線条体に光を照射して線条体投射ニューロンを興奮させたところ、黒質網様部では光刺激に対して一過性の「抑制-遅い興奮」という二相性の応答が認められた。この二相性の応答は、L-DOPA誘発性ジスキネジアを示すマウスの「抑制-遅い興奮」と非常に類似していた。また、L-DOPAでジスキネジアを誘発したパーキンソン病モデルマウスに対して、線条体投射ニューロンを抑制したところ、ジスキネジアが抑えられる傾向が認められた。これらの結果から、線条体投射ニューロンの神経活動は、L-DOPA誘発性ジスキネジアに重要な役割を果たしていることが示唆された。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (18 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] The effects of zonisamide on L-DOPA-induced dyskinesia in Parkinson's disease model mice2019

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

      Neurochemistry International

      Volume: 124 Pages: 171-180

    • DOI

      10.1016/j.neuint.2019.01.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4.2019

    • Author(s)
      Okada Y, Sumioka T, Ichikawa K, Sano H, Nambu A, Kobayashi K, Uchida K, Suzuki Y, Tominaga M, Reinach PS, Hirai SI, Jester JV, Miyajima M, Shirai K, Iwanishi H, Kao WW, Liu CY, Saika S.
    • Journal Title

      Lab Invest.

      Volume: 99(2) Issue: 2 Pages: 210-230

    • DOI

      10.1038/s41374-018-0118-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration.2018

    • Author(s)
      Kaneko N, Herranz-Perez V, Otsuka T, Sano H, Ohno N, Omata T, Nguyen HB, Thai TQ, Nambu A, Kawaguchi Y, Garcia-Verdugo JM, Sawamoto K.
    • Journal Title

      Science Advances

      Volume: 4 Issue: 12 Pages: 0618-0618

    • DOI

      10.1126/sciadv.aav0618

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monitoring and updating of action selection for goal-directed behavior through the striatal direct and indirect pathways2018

    • Author(s)
      Nonomura S, Nishizawa K, Sakai Y, Kawaguchi Y, Kato S, Uchigashima M, Watanabe M, Yamanaka K, Enomoto K, Chiken S, Sano H, Soma S, Yoshida J, Samejima K, Ogawa M, Kobayashi K, Nambu A, Isomura Y, Kimura M
    • Journal Title

      Neuron

      Volume: 99(6) Issue: 6 Pages: 1302-1314

    • DOI

      10.1016/j.neuron.2018.08.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optogenetic Activation of the Sensorimotor Cortex Reveals “Local Inhibitory and Global Excitatory” Inputs to the Basal Ganglia2017

    • Author(s)
      Ozaki Mitsunori、Sano Hiromi、Sato Shigeki、Ogura Mitsuhiro、Mushiake Hajime、Chiken Satomi、Nakao Naoyuki、Nambu Atsushi
    • Journal Title

      Cerebal Cortex

      Volume: 27 Issue: 12 Pages: 5716-5726

    • DOI

      10.1093/cercor/bhx234

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Striatonigral direct pathway activation is sufficient to induce repetitive behaviors2017

    • Author(s)
      Bouchekioua Youcef、Tsutsui-Kimura Iku、Sano Hiromi、Koizumi Miwako、Tanaka Kenji F.、Yoshida Keitaro、Kosaki Yutaka、Watanabe Shigeru、Mimura Masaru
    • Journal Title

      Neuroscience Research

      Volume: 17 Pages: 30454-30456

    • DOI

      10.1016/j.neures.2017.09.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Physiological and anatomical organization of cortico-striatal inputs in the basal ganglia2019

    • Author(s)
      Hiromi Sano, Kenta Kobayashi, Shigeki Kato, Satomi Chiken, Kazuto Kobayashi, Atsushi Nambu
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] Neuronal responses and movements induced by concurrent activation of striatonigral and striatopallidal neurons2018

    • Author(s)
      Hiromi Sano, Kenji F Tanaka, Atsushi Nambu
    • Organizer
      FENS2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Information flow for motor control by striatal projection neurons2018

    • Author(s)
      Hiromi Sano
    • Organizer
      Stockholm-Okazaki Workshop on Multi-scale dynamice of basal ganglian in brain function and dysfunction
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大脳皮質-線条体路の興奮誘導に対する大脳基底核の応答2018

    • Author(s)
      佐野裕美
    • Organizer
      2017年度第3回大脳基底核機能研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Physiological roles of striatal projection neurons revealed by optogenetics2018

    • Author(s)
      Hiromi Sano, Atsushi Nambu
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cortico-striatal induced responses in the basal ganglia2017

    • Author(s)
      Hiromi Sano, Kenta Kobayashi, Shigeki Sato, Satomi Chiken, Kazuto Kobayashi, Atsushi Nambu
    • Organizer
      International symposium, Neural Oscillation Conference 2017, Problems of Consciousness and Neuropsychiatric Disorders as Network Diseases
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Inhibitory center-excitatory surround" inputs from the motor cortex to the globus pallidus revealed by optogenetic stimulation2017

    • Author(s)
      Atsushi Nambu, Mitsunori Ozaki, Hiromi Sano, Shigeki Sato, Mitsuhiro Ogura, Hajime Mushiake, Satomi Chikenm Naoyuki Nakao
    • Organizer
      International symposium, Neural Oscillation Conference 2017, Problems of Consciousness and Neuropsychiatric Disorders as Network Diseases
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Responses in the basal ganglia induced by cortico-striatal neurons2017

    • Author(s)
      Hiromi Sano, Kenta Kobayashi, Shigeki Kato, Satomi Chiken, Kazuto Kobayashi, Atsushi Nambu
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Functional analysis of Rho/Rho-kinase signaling pathway in corticostriatal neuron survival using a new gene delivery system2017

    • Author(s)
      Kenta Kobayash, Hiromi Sano, Shigeki Kato, Keisuke Kuroda, Shinichi Nakamuta, Tadashi Isa, Atsushi Nambu, Kozo Kaibuchi, Kazuto Kobayashi
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス神経麻痺性角膜症モデルに対する三叉神経節でのTRPV4強制発現による治療効果2017

    • Author(s)
      岡田由香、富永真琴、佐野裕美、小林憲太、南部篤、雑賀司珠也
    • Organizer
      第47回日本創傷治癒学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cortico-striata neurons induced responses in the basal ganglia2017

    • Author(s)
      Hiromi Sano
    • Organizer
      NIPS-CIN Joint Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Concurrent activation of striatal medium spiny neurons induces involuntary movements similar to L-DOPA induced dyskinesia2017

    • Author(s)
      Hiromi Sano, Kenji F Tanaka, Atsushi Nambu
    • Organizer
      International Symposium on Adaptive Circuit Shift 2017, Behavioral adaptation and functional recovery from pathological states
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2019-12-27  

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