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Elucidation of molecular mechanism of synaptic plasticity by kinetic analysis of receptor trafficking

Research Project

Project/Area Number 23500472
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

YAMAGUCHI Kazuhiko  独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (00191221)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords小脳 / 運動学習 / シナプス可塑性 / 長期抑圧 / グルタミン酸受容体 / エキソサイトーシス / エンドサイトーシス / 数理モデル / プルキンエ細胞 / 学習 / スパイン / AMPA受容体 / トラフィッキング / LTD / ケージ化ペプチド
Research Abstract

Long-term depression (LTD) of synaptic transmission provides a mechanism of motor leaning, and as a mechanism of LTD, destabilization and consequent elimination of glutamate receptor (GluR) via endocytosis has been proposed, however, no quantitative examination has been performed. Here, stable pool size of GluR and its destabilization upon LTD was quantified, and rate constant of endocytosis of GluR was measured and compared between before and after LTD-induction. Then, I developed a mathematical model of GluR trafficking upon LTD, which predicts partial loss of recycling internal pool of GluR. Image analysis of GluR, tagged by fluorescent protein, indicated translocation of internal GluR from the spine to the dendritic shaft upon LTD, which is consistent with the prediction by the mathematical model of GluR trafficking in cerebellar Purkinje cell.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (29 results)

All 2014 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (25 results) (of which Invited: 1 results)

  • [Journal Article] Long-term depression as a model of cerebellar plasticity2014

    • Author(s)
      Ito M, Yamaguchi K, Nagao S, Yamazaki T
    • Journal Title

      Progress in Brain Research

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Long-term depression as a model of cerebellar plasticity2014

    • Author(s)
      Ito M, yamaguchi K, Nagao S, Yamazaki, T.
    • Journal Title

      Progress in Brain research

      Volume: 210 Pages: 1-30

    • DOI

      10.1016/b978-0-444-63356-9.00001-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation2011

    • Author(s)
      Kaneko, M., Yamaguchi, K., Eiraku, M., Sato, M., Takata, N., Kiyohara, Y., Mishina, M., Hirase, H., Hashikawa, T. and Kengaku, M
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 5 Pages: e20108-e20108

    • DOI

      10.1371/journal.pone.0020108

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] CRMP5(collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the cerebellar Purkinje cells2011

    • Author(s)
      Yamashita N, Mosinger B, Roy A, Miyazaki M, Ugajin K, Nakamura F, Sasaki Y, Yamaguchi K, Kolattukudy P, Goshima Y.
    • Journal Title

      Journal of Neuroscience

      Volume: 31(5) Issue: 5 Pages: 1773-79

    • DOI

      10.1523/jneurosci.5337-10.2011

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 小脳プルキンエ細胞長期抑圧で内在化した AMPA 受容体の細胞内分布2014

    • Author(s)
      山口和彦
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-03-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Nitric oxide dependent change in AMPA receptor trafficking in Purkinje cell analysed using a kinetic model of receptor trafficking2014

    • Author(s)
      Yamaguchi K
    • Organizer
      the 37th Congress of the International Union of Physiological Sciences (IUPS 2013)
    • Place of Presentation
      Birmingham UK
    • Year and Date
      2014-03-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 小脳平行線維-プルキンエ細胞間シナプスにおける AMPA 受容体トラフィッキングに対する側方拡散の寄与2013

    • Author(s)
      山口和彦, 永雄総一
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 受容体側方拡散の小脳プルキンエ細胞シナプスにおけるAMPA受容体トラフィッキングへの寄与2013

    • Author(s)
      山口 和彦
    • Organizer
      生理学研究所 研究会 「シナプス・神経ネットワークの機能ダイナミクス」
    • Place of Presentation
      岡崎      愛知
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 小脳平行線維プルキンエ細胞間シナプス長期増強におけるAMPA 受容体トラフィッキングのキネティック解析2012

    • Author(s)
      山口和彦, 永雄総一
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Change in trafficking kinetics of AMPA-receptor underlying LTD revealed by photolysis of caged inhibitory peptide in cerebellar Purkinje cell2012

    • Author(s)
      Yamaguchi, K. Nagao, S
    • Organizer
      8th Federation of European Neuroscience Forum of Neuroscience
    • Place of Presentation
      Barcelona Spain
    • Year and Date
      2012-07-16
    • Related Report
      2013 Final Research Report
  • [Presentation] ケージ化阻害ペプチドを用いた受容体トラフィッキングのキネティック解析により解明された小脳 LTD における AMPA 受容体エキソサイトーシスの抑制2012

    • Author(s)
      山口和彦, 永雄総一
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本
    • Year and Date
      2012-03-31
    • Related Report
      2013 Final Research Report
  • [Presentation] Suppression of AMPA-receptor endocytosis is the mechanism underlying LTP at the parallel fiber-Purkinje cell synapse.2012

    • Author(s)
      Yamaguchi K, Nagao S.
    • Organizer
      International Synapse Research Workshop 2012 Understanding of synapse pathology, from genome mutation to functional defects.
    • Place of Presentation
      Okazaki, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] ケージ化阻害ペプチドを用いた受容体トラフィッキングのキネティック解析により解明された小脳LTDにおけるAMPA受容体エキソサイトーシスの抑制2012

    • Author(s)
      Yamaguchi K, Nagao S.
    • Organizer
      第89回日本生理学会大会シンポジウム
    • Place of Presentation
      松本
    • Related Report
      2011 Research-status Report
  • [Presentation] An analysis based on a data-driven kinetic model of receptor-trafficking in cerebellar Purkinje cell predicts insufficiency of receptor-destabilization as a mechanism of LTD2011

    • Author(s)
      Yamaguchi, K., Nagao, S
    • Organizer
      The 11th Japan-Korea- China Joint Workshop on Neurobiology and Neuroinformatics
    • Place of Presentation
      Okinawa
    • Year and Date
      2011-12-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Multi-site modulation of AMPA-receptor trafficking during cerebellar LTD2011

    • Author(s)
      Yamaguchi K and Nagao S
    • Organizer
      4th International Symposium of the Society for Research on the Cerebellum
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-09-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Lrfn2/SALM1 regulates excitatory synapse function in the hippocampus and its deficient mice display mental disorder-like behavioral abnormalities2011

    • Author(s)
      Morimura N, Yasuda H, Yamada K, Tomioka N, Katayama K, Yamaguchi K, Ota M, Kamiya A, Aruga J
    • Organizer
      Symposium : Emerging synapse organizers in hippocampal neural circuits 34th Ann. Meeting of Jpn Neurosci. Soc
    • Place of Presentation
      Yokohama
    • Year and Date
      2011-09-15
    • Related Report
      2013 Final Research Report
  • [Presentation] AMP 型受容体エクソサイトーシスの活動依存性抑圧の平行線維-プルキンエ細胞間シナプスにおける長期抑圧発現への関与2011

    • Author(s)
      山口和彦, 達 吉郎, 永雄総一
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Activity-dependent Change in AMPA- receptor trafficking investigated by photolysis of a caged inhibitory peptide in cerebellar Purkinje cell2011

    • Author(s)
      Yamaguchi.K, Tatsu Y, Nagao S. Ito M
    • Organizer
      8th IBRO World Congress of Neurosci
    • Place of Presentation
      Florence Italy
    • Year and Date
      2011-07-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 小脳プルキンエ細胞における構成性および活動依存性 AMPA 受容体トラフィッキングのデータ駆動性キネティックモデル2011

    • Author(s)
      山口和彦, 達 吉郎, 永雄総一
    • Organizer
      第88回日本生理学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Activity-dependent Change in AMPA-Receptor Trafficking Investigated by Photolysis of a Caged Inhibitory Peptide in Cerebellar Purkinje Cell.2011

    • Author(s)
      Yamaguchi.K, Tatsu Y, Nagao S. Ito M.
    • Organizer
      8th IBRO World Congress of Neurosci.
    • Place of Presentation
      Florence Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] Multi-site modulation of AMPA-receptor trafficking during cerebellar LTD.2011

    • Author(s)
      Yamaguchi K and Nagao S.
    • Organizer
      4th International Symposium of the Society for Research on the Cerebellum
    • Place of Presentation
      Tokyo Japan
    • Related Report
      2011 Research-status Report
  • [Presentation] An analysis based on a data-driven kinetic model of receptor-trafficking in cerebellar Purkinje cell predicts insufficiency of receptor-destabilization as a mechanism of LTD.2011

    • Author(s)
      Yamaguchi, K., Nagao, S.
    • Organizer
      The 11th Japan-Korea-China Joint Workshop on Neurobiology and Neuroinformatics
    • Place of Presentation
      Okinawa Japan
    • Related Report
      2011 Research-status Report
  • [Presentation] AMPA型受容体エクソサイトーシスの活動依存性抑圧の平行線維-プルキンエ細胞間シナプスにおける長期抑圧発現への関与.2011

    • Author(s)
      山口和彦、達 吉郎、永雄総一
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Changes in kinetic parameters of receptor trafficking underlying synaptic plasticity in cerebellum

    • Author(s)
      Yamaguchi K.
    • Organizer
      Molecular and Cellular Cognition Society (MCCS-Asia 6th Annual Meeting in Kyoto
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Nitric oxide dependent change in AMPA receptor trafficking in Purkinje cell analysed using a kinetic model of receptor trafficking

    • Author(s)
      Yamaguchi K.
    • Organizer
      the 37th Congress of the International Union of Physiological Sciences (IUPS 2013)
    • Place of Presentation
      Birmingham UK
    • Related Report
      2013 Annual Research Report
  • [Presentation] 小脳プルキンエ細胞長期抑圧で内在化したAMPA受容体の細胞内分布

    • Author(s)
      山口 和彦
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
  • [Presentation] Change in trafficking kinetics of AMPA-receptor underlying LTD revealed by photolysis of caged inhibitory peptide in cerebellar Purkinje cell

    • Author(s)
      Yamaguchi, K. Nagao, S.
    • Organizer
      8th Federation of European Neuroscience Forum of Neuroscience
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2012 Research-status Report
  • [Presentation] Suppression of AMPA-receptor-exocytosis during cerebellar LTD revealed by kinetic analysis of receptor trafficking using caged inhibitory peptide

    • Author(s)
      Yamaguchi K, Nagao S.
    • Organizer
      Symposium "Chemical neurobiology" 89th Annual Meeting of Jpn Physiol. Soc.
    • Place of Presentation
      Matsumoto, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Kinetic analysis of AMPA type glutamate receptors trafficking upon LTP at the parallel fiber-Purkinje cell synapse in cerebellum

    • Author(s)
      Yamaguchi K, Nagao S.
    • Organizer
      35th Anual Meeting of Jpn Society for Neuroscience
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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