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Study on molecular mechanism of cerebellar circuit formation

Research Project

Project/Area Number 25290021
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionShinshu University

Principal Investigator

UEMURA Takeshi  信州大学, 学術研究院医学系, 准教授 (00372368)

Co-Investigator(Renkei-kenkyūsha) YOSHIDA Tomoyuki  富山大学, 医学薬学研究院, 准教授 (90372367)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords脳・神経 / 小脳 / 神経回路網構築 / 神経回路網形成
Outline of Final Research Achievements

Synapses are formed and maintained by trans-synaptic interaction between pre- and postsynaptic cell adhesion molecules. In the cerebellum, the trans-synaptic interaction of postsynaptic glutamate receptor GluRδ2 and presynaptic neurexins (Nrxns) through cerebellin precursor protein 1 (Cbln1) mediates parallel fiber (PF)-Purkinje cell (PC) synapse formation. In mammals, Nrxns are encoded by three genes (Nrxn1, Nrxn2, and Nrxn3). In this study, we generated cerebellar granule cell (GC)-specific Nrxn1, Nrxn2, and Nrxn3 triple KO mice. The cerebellar GCs-specific Nrxns triple KO mice showed severe ataxia and reduced cerebellar size. Histological analysis revealed that the number of cerebellar GCs was dramatically decreased in the cerebellar GCs-specific Nrxns triple KO mice. Electron microscopic analysis showed that PF-PC synapses were disappeared in the GCs-specific Nrxns triple KO mice. These results suggest that Nrxns are essential for cerebellar circuit formation.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Invited: 4 results) Book (1 results)

  • [Journal Article] In situ screening for postsynaptic cell adhesion molecules during synapse formation.2017

    • Author(s)
      Uemura T, Maeda A, Yasumura M, Shimada T, Fukata Y, Fukata M, Yoshida T
    • Journal Title

      Journal of Biochemistry

      Volume: 印刷中 Pages: 295-302

    • DOI

      10.1093/jb/mvx030

    • NAID

      40021380573

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescent protein tagging of endogenous protein in brain neurons using CRISPR/Cas9-mediated knock-in and in utero electroporation techniques.2016

    • Author(s)
      Uemura T, Mori T, Kurihara T, Kawase S, Koike R, Satoga M, Cao X, Li X, Yanagawa T, Sakurai T, Shindo T, Tabuchi K.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 35861-35861

    • DOI

      10.1038/srep35861

    • NAID

      120007100133

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mechanisms of splicing-dependent trans-synaptic adhesion by PTPδ-IL1RAPL1/IL-1RAcP for synaptic differentiation2015

    • Author(s)
      Yamagata A., Yoshida, T., Sato, Y., Goto-Ito, S., Uemura, T., Maeda, A., Shiroshima, T., Iwasawa-Okamoto, S., Mori, H., Mishina, M., Fukai , S.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6926-6926

    • DOI

      10.1038/ncomms7926

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IL1RAPL1 knockout mice show learning deficiency, memory decline, hyperactivity and reduced anxiety-like behaviours.2014

    • Author(s)
      Misato Yasumura, Tomoyuki Yoshida, Maya Yamazaki, Manabu Abe, Rie Natsume, Kouta Kanno, Takeshi Uemura, Keizo Takao, Kenji Sakimura, Takefumi Kikusui, Tsuyoshi Miyakawa, Masayoshi Mishina
    • Journal Title

      Scientific Reports

      Volume: 4: 6613 Issue: 1 Pages: 6613-6613

    • DOI

      10.1038/srep06613

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Striatal dopamine D1 receptor is essential for contextual fear conditioning2014

    • Author(s)
      Masaru Ikegami, Takeshi Uemura, Ayumi Kishioka, Kenji Sakimura and Masayoshi Mishina
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 3976-3976

    • DOI

      10.1038/srep03976

    • NAID

      120007100114

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Consolidation of auditory fear memories formed by weak unconditioned stimuli requires NMDA receptor activation and de novo protein synthesis in the striatum2013

    • Author(s)
      Kishioka A, Uemura T, Fukushima F, Mishina M
    • Journal Title

      Mol. Brain

      Volume: 6 Issue: 1 Pages: 17-17

    • DOI

      10.1186/1756-6606-6-1

    • NAID

      120007100115

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular Mechanism of Synapse Formation by Synaptic Organizer2013

    • Author(s)
      植村 健
    • Journal Title

      Seibutsu Butsuri

      Volume: 53 Issue: 2 Pages: 090-093

    • DOI

      10.2142/biophys.53.090

    • NAID

      10031151788

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] RISPR/Cas9-mediated gene knock-in in single neurons in vivo2016

    • Author(s)
      植村健, 森琢磨, 栗原大河, 里賀みちる, 田渕克彦
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜市、パシフィコ横浜
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Slitrkファミリータンパク質とIIa型受容体タンパク質チロシン脱リン酸化酵素がスプライスインサートに依存して相互作用するメカニズム2015

    • Author(s)
      山形敦史、佐藤裕介、伊藤-後藤桜子、植村健、吉田知之、深井周也
    • Organizer
      第88回日本生化学大会
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Insights into structure and assembly of GluD2-Cbln1-neurexin adhesion complex for cerebellar synapse formation2015

    • Author(s)
      Takeshi Uemura
    • Organizer
      第88回日本生化学大会
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] IIa 型受容体チロシンホスファターゼδ とインターロイキン1受容体タイプのシナプスオーガナイザー間の選択的スプラシング依存的相互作用制御の構造基盤2015

    • Author(s)
      山形敦史、吉田知之、佐藤裕介、伊藤-後藤桜子、植村健、森寿、三品昌美、深井周也
    • Organizer
      第88回日本生化学大会
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 小脳シナプス形成を担うGluRδ2-Cbln1-neurexin接着分子複合体の構造基盤2015

    • Author(s)
      植村健
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      石川県金沢市「金沢大学」
    • Year and Date
      2015-09-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Structural analysis of GluRδ2-Cbln1-Neurexin complex for cerebellar synapse formation2015

    • Author(s)
      Takeshi Uemura, Yusuke Sato, Atsushi Yamagata, Tomoyuki Yoshida, Sakurako Goto-Ito, Katsuhiko Tabuchi, Masayoshi Mishina, Shuya Fuka
    • Organizer
      Neuro2015
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Structural basis of IL1RAPL1-PTPδ complex for neuronal synaptogenesis2015

    • Author(s)
      Tomoyuki Yoshida, Atsushi Yamagata, Yusuke Sato, Sakurako Ito:, Takeshi Uemura, Asami Maeda, Tomoko Shiroshima, Shiho Okamoto, Hisashi Mori, Masayoshi Mishina, Shuya Fukai
    • Organizer
      Neuro2015
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] tructural basis of the splicing dependent interaction between Slitrk2 and PTPδ2015

    • Author(s)
      Atsushi Yamagata, Yusuke Sato, Sakurako Goto-Ito, Takeshi Uemura, Asami Maeda, Tomoko Shiroshima, Tomoyuki Yoshida, Shuya Fuka
    • Organizer
      Neuro2015
    • Place of Presentation
      兵庫県神戸市 「神戸国際会議場」
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] C1qファミリー分子Cbln1とその受容体であるグルタミン酸受容体GluRδ2とneurexinによる小脳シナプス形成の調節2014

    • Author(s)
      植村 健
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 線条体ドパミンD1受容体は文脈依存怖条件付け学習に必須である2014

    • Author(s)
      三品昌美、池上賢、植村健、岸岡歩、崎村建司
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] The Atmospheric Scanning Electron Microscope (ASEM) Observes Axonal Segmentation and Synaptic Induction in Solution2014

    • Author(s)
      2.佐藤 主税, 木下 貴明, 植村 健, 平野 和己, 川田 正晃, 西山英利, 佐藤 真理, 海老原 達彦, 須賀三雄, 西原祥子
    • Organizer
      2014 Microscopy & Microanalysis meeting
    • Place of Presentation
      ハートフォード, アメリカ合衆国
    • Year and Date
      2014-08-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] シナプス形成を司る GluRδ2-Cbln1-Neurexin三者複合体の構造解析2014

    • Author(s)
      植村 健
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      ワークピア横浜/横浜産貿ホール マリネリア(神奈川県横浜市)
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 受容体でコートした磁気ビーズによる初代培養シナプス形成誘導のASEM水中免疫電顕2014

    • Author(s)
      植村健、佐藤真理、西山英利、須賀三雄、佐藤主税
    • Organizer
      日本顕微鏡学会第70回記念学術講演会
    • Place of Presentation
      幕張メッセ国際会議場(千葉県千葉市)
    • Year and Date
      2014-05-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] IL1RAPL1欠損マウスの行動学的解析2013

    • Author(s)
      安村美里, 吉田知之, 高雄啓三, 山崎真弥, 阿部学, 植村健, 宮川剛, 崎村建司, 三品昌美
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2013-06-21
    • Related Report
      2013 Annual Research Report
  • [Book] Synapse formation in the brain. Cortical Development. Neural Diversity and Neocortical Organization2013

    • Author(s)
      Mishina M, Yoshida T, Yasumura M, Uemura T
    • Total Pages
      282
    • Publisher
      Springer Japan
    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2018-03-22  

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