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Long-lasting synaptic plasticity mediated by yin-yang effect of BDNF and proBDNF

Research Project

Project/Area Number 23300132
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

OGURA Akihiko  大阪大学, 生命機能研究科, 教授 (30260631)

Co-Investigator(Kenkyū-buntansha) TOMINAGA Keiko (YOSHINO Keiko)  大阪大学, 大学院・生命機能研究科, 准教授 (60256196)
Co-Investigator(Renkei-kenkyūsha) KOJIMA Masami  産業技術総合研究所, 関西センターセルエンジニアリング研究部門, グループ長 (40344171)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords記憶 / シナプス新生 / シナプス廃止 / BDNF / proBDNF / 脳切片培養 / 記憶固定 / 構造可塑性 / シナプス可塑性 / 長期記憶 / 恐怖学習 / 遺伝子改変マウス / TrkB / p75 / ゆらぎ
Research Abstract

Brain memory is established through 2 steps; acquisition and consolidation, the cellular mechanisms of the former step have been well analyzed using LTP (long-term potentiation) and LTD (long-term depression) as model phenomena for analysis, while those of the latter remain unclear. We previously reported in the stable cultures of hippocampal slice that 3 repeated inductions of LTP and LTD lead to the long-lasting strengthening and weakening of neuronal circuit supported by new synapse formation and elimination, respectively. In the present research, we demonstrated that the synapse formation is mediated by a BDNF (brain-derived neurotrophic factor)-TrkB signaling pathway, while the synapse elimination is mediated by a proBDNF (precursor protein of BDNF)-p75 pathway. Since BDNF and proBDNF are the products of a single gene, the apparently opposite cellular events are regulated by epigenetic regulation, this fact may provoke a paradigm shift in memory research.

Report

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

    (59 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 13 results) Presentation (38 results) (of which Invited: 1 results) Book (5 results) Remarks (1 results)

  • [Journal Article] 記憶固定の細胞生物学2014

    • Author(s)
      小倉明彦, 冨永恵子
    • Journal Title

      科学

      Volume: 83 Pages: 256-262

    • Related Report
      2013 Final Research Report
  • [Journal Article] 記憶固定機構の細胞生物学2014

    • Author(s)
      小倉明彦、冨永(吉野)恵子
    • Journal Title

      科学

      Volume: 84 Pages: 256-262

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Dendritic spine dynamics in synaptogenesis after repeated LTP inductions : Dependence on pre-existing spine density2013

    • Author(s)
      Oe Y, Tominaga-Yoshino K, Hasegawa S, Ogura A
    • Journal Title

      Sci. Rep

      Volume: 3 Issue: 1 Pages: 1957-1957

    • DOI

      10.1038/srep01957

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of TrkBand p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity2013

    • Author(s)
      Sakuragi S, Tominaga-Yoshino K, Ogura A
    • Journal Title

      Sci. Rep

      Volume: 3 Issue: 1 Pages: 3158-3158

    • DOI

      10.1038/srep03158

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 長期記憶の細胞機構解明を目指して2013

    • Author(s)
      冨永恵子, 小倉明彦
    • Journal Title

      日薬理誌

      Volume: 142 Pages: 122-127

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity2013

    • Author(s)
      Sakuragi, S., Tominaga-Yoshino, K. & Ogura, A.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1

    • DOI

      10.1038/srep03185

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 記憶固定のin vitro 再現:長期記憶の細胞基盤解明をめざして2013

    • Author(s)
      冨永(吉野)恵子、小倉明彦
    • Journal Title

      日本薬理学会雑誌

      Volume: 142 Pages: 122-127

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simplified method to generate serotonergic neurons from mouse embryonic stem and induced pluripotent stem cells2012

    • Author(s)
      Shimada T,Takai Y, Shinohara K, Yamasaki A, Tominaga-Yoshino K, Ogura A, Toi A, Asano K, Shintani N, Hayata-Takano A, Baba A, Hashimoto H
    • Journal Title

      J. Neurochem

      Volume: 122 Pages: 81-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A simplified Method to Generate Serotonergic Neurons from mouse Embryonic Stem and Induced Pluripotent stem cells2012

    • Author(s)
      Shimada T, Takai Y, Shinohara K, Yamasaki A, Tominaga-Yoshino K, Ogura A, Toi A, Asano K, Shintani N, Hayata-Takano A, Baba A, Hashimoto H
    • Journal Title

      Journal of Neurochemistry

      Volume: 122 Issue: 1 Pages: 81-93

    • DOI

      10.1111/j.1471-4159.2012.07724.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local establishment of repetitive-LTP-induced synaptic enhancement in cultured hippocampal slices with divided input pathways2011

    • Author(s)
      Oe Y, Tominaga-Yoshino K, Ogura A
    • Journal Title

      J. Neurosci. Res

      Volume: 89 Pages: 1419-1430

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of creatine and its analogue, beta-guanidinopropionic acid on the differentiation and nucleoli in myoblasts2011

    • Author(s)
      Ohira Y, Matsuoka Y, Kawano F, Ogura A, Higo Y, Ohira T, Terada M, Oke Y, Nakai N
    • Journal Title

      Biosci. Biotech. Biochem

      Volume: 75 Pages: 1085-1089

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Region-specific responses of adductor longus muscle to gravitational load-dependent activity in Wistar Hannover rats2011

    • Author(s)
      Ohira T, Wang X, D, Terada M, Kawano F, Nakai N, Ogura A, Ohira Y
    • Journal Title

      PLoS ONE

      Volume: 6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of creatine and its analogue, beta-guanidinopropionic acid on the differentiation and nucleoli in myoblasts2011

    • Author(s)
      Ohira, Y., Matsuoka, Y., Kawano, F., Ogura, A., Higo, Y., Ohira, T., Terada, M., Oke, Y., Nakai, N.
    • Journal Title

      Biosci.Biotech.Biochem.

      Volume: 75 Pages: 1085-1089

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local establishment of repetitive-LTP-induced synaptic enhancement in cultured hippocampal slices with divided input pathways2011

    • Author(s)
      Oe, Y., Tominaga Yoshino, K., Ogura, A.
    • Journal Title

      J.Neurosci.Res.

      Volume: 89 Pages: 1419-1430

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Region-specific responses of adductor longus muscle to gravitational load-dependent activity in Wistar Hannover rats2011

    • Author(s)
      Ohira, T., Wang, X.D., Terada, M., Kawano, E, Nakai, N., Ogura, A., Ohira, Y.
    • Journal Title

      PLoS ONE

      Volume: 6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] RISE(繰り返しLTP 誘発後の長期シナプス強化)の生理的意義 : 個体での検討2014

    • Author(s)
      永岡昭吾, 浦久保知佳, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Final Research Report
  • [Presentation] RISE(繰り返しLTP誘発後の長期シナプス強化)の生理的意義:個体での検討2014

    • Author(s)
      永岡昭吾、浦久保知佳、冨永(吉野)恵子、小倉明彦
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
  • [Presentation] 繰り返しLTD 誘発後の長期持続的シナプス減弱におけるスパイン動態2013

    • Author(s)
      長谷川翔, 大江祐樹, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本生理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] BDNF とその前駆体分子の作用による対照的な長期可塑性2013

    • Author(s)
      桜木繁雄, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経科学学会・日本神経化学会合同大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 繰り返しLTD 誘発後の長期持続性シナプス減弱での海馬錐体細胞樹状突起棘の動態2013

    • Author(s)
      長谷川翔, 大江祐樹, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経科学学会・日本神経化学会合同大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 苔状線維CA3 間シナプスで繰り返し長期増強の誘発後に生起する可塑的変化2013

    • Author(s)
      有賀理瑛, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経科学学会・日本神経化学会合同大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Asymmetric dendritic spine dynamics in the apparently symmetric long-lasting synaptic plasticity phenomena after repeated LTP/LTD inductions2013

    • Author(s)
      Hasegawa, S., Oe, Y., Tominaga-Yoshino, K., Ogura, A
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2013 Final Research Report
  • [Presentation] 繰り返しLTD 誘発後の長期持続的シナプス減弱(LOSS)生起時の樹状突起棘の動態2013

    • Author(s)
      長谷川翔, 冨永-吉野恵子, 小倉明彦
    • Organizer
      生理研研究会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Final Research Report
  • [Presentation] BDNFとその前駆体分子の作用による対照的な長期シナプス可塑性2013

    • Author(s)
      桜木繁雄、冨永(吉野)恵子、小倉明彦
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 繰り返しLTD誘発後の長期持続性シナプス減弱での海馬錐体細胞樹状突起棘の動態2013

    • Author(s)
      長谷川翔、大江祐樹、冨永(吉野)恵子、小倉明彦
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 苔状線維CA3間シナプスで繰り返し長期増強の誘発後に生起する可塑的変化2013

    • Author(s)
      有賀理瑛、冨永(吉野)恵子、小倉明彦
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Asymmetric dendritic spine dynamics in the apparently symmetric long-lasting synaptic plasticity phenomena after repeated LTP/LTD inductions2013

    • Author(s)
      Hasegawa, S., Oe, Y., Tominaga-Yoshino, K. & Ogura, A.
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dendritic spine dynamics in the long-lasting synaptic suppression after repetitive LTD induction2013

    • Author(s)
      Hasegawa S et al.
    • Organizer
      90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] 苔状線維-CA3 間シナプスで繰り返し長期増強の誘発が引き起こす長期シナプス強化の可能性2012

    • Author(s)
      有賀理瑛, 谷本浩亀, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経化学会
    • Place of Presentation
      神戸
    • Year and Date
      2012-09-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 培養ラット小脳顆粒細胞の生存に対する共存橋核の影響と代謝型グルタミン酸受容体の関与2012

    • Author(s)
      長谷川卓也, 小倉明彦, 冨永-吉野恵子, 志賀千明
    • Organizer
      日本生理学会
    • Place of Presentation
      松本
    • Related Report
      2013 Final Research Report
  • [Presentation] Ca 透過型AMPA 受容体の阻害はスパイン新生と長期可塑性をともに抑制する2012

    • Author(s)
      浦久保知佳, 河合克宏, 小倉明彦, 冨永-吉野恵子
    • Organizer
      日本生理学会
    • Place of Presentation
      松本
    • Related Report
      2013 Final Research Report
  • [Presentation] 海馬培養切片での長期シナプス可塑性におけるBDNF-TrkB 信号経路の関与2012

    • Author(s)
      桜木繁雄, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経科学学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of the BDNF-TrkB signaling pathway in the long-lasting synaptic plasticity in hippocampal slice cultures2012

    • Author(s)
      Sakuragi, S., Tominaga-Yoshino, K., Ogura, A
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      New Orleans
    • Related Report
      2013 Final Research Report
  • [Presentation] 繰り返しLTP・LTD 誘発後のシナプス新生・廃止現象とBDNF・proBDNF シグナリング2012

    • Author(s)
      桜木繁雄, 冨永-吉野恵子, 小倉明彦
    • Organizer
      生理研研究会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Final Research Report
  • [Presentation] Possibility of repetitive LTP-induced long-lasting synaptic plasticity in the mossy fiber-CA3 pathway2012

    • Author(s)
      Ariga R et al.
    • Organizer
      55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Involvement of the BDNF-TrkB signaling pathway in the long-lasting synaptic plasticity in hippocampal slice cultures2012

    • Author(s)
      Sakuragi S et al.
    • Organizer
      35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Two opposite forms of long-lasting synaptic plasticity explained by yin-yang effects of BDNF and its precursor2012

    • Author(s)
      Sakuragi S et al.
    • Organizer
      2012 Meeting of the Society for Neuroscience
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] BDNF/proBDNF signaling in the repetitive LTP/LTD-induced long-lasting synaptic plasticity2012

    • Author(s)
      Sakuragi S et al.
    • Organizer
      Seiriken Kenkyukai
    • Place of Presentation
      Okazaki, Japan
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Imbalance in gain and loss of dendritic spines after repeated LTP induction2011

    • Author(s)
      Oe,Y., Tominaga-Yoshino, K., Ogura, A.
    • Organizer
      42^<nd> Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Dorsoventral bias of active neuronal population as an index of information transfer related to memory storage2011

    • Author(s)
      Nakamura, E., Matsuzaki, T., Ogura, A., Tominaga-Yoshino, K.
    • Organizer
      42^<nd> Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] 切片培養での長期シナプス増強におけるBDNF放出の関与2011

    • Author(s)
      櫻木繁雄、冨永-吉野恵子、小倉明彦
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      石川県
    • Year and Date
      2011-09-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 大脳皮質における海馬依存的な記憶固定のインビトロ再現の試み2011

    • Author(s)
      川上拓宏、小倉明彦、冨永-吉野恵子
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      石川県
    • Year and Date
      2011-09-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 長期可塑性成立過程のシナプス形成とAMPA受容体GluR1サブユニットの動態2011

    • Author(s)
      浦久保知佳、河合克宏、小倉明彦、冨永-吉野恵子
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜市
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規スパインの形成は樹状突起のスパイン密度に依存する2011

    • Author(s)
      大江祐樹、冨永-吉野恵子、小倉明彦
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜市
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Input-pathway specific establishment of repetitive-LTP-induced long-lasting synaptic enhancement in cultured hippocampal slices2011

    • Author(s)
      Oe, Y., Tominaga-Yoshino, K., Ogura, A.
    • Organizer
      8^<th> IBRO World Congress of Neuroscience
    • Place of Presentation
      フィレンツェ(イタリア)
    • Year and Date
      2011-07-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Input-pathway specific establishment of repetitive-LTP-induced long-lasting synaptic enhancement in cultured hippocampal slices2011

    • Author(s)
      Oe, Y., Tominaga-Yoshino, K., Ogura, A
    • Organizer
      IBRO World Congress of Neuroscience
    • Place of Presentation
      Florence
    • Related Report
      2013 Final Research Report
  • [Presentation] 長期可塑性成立過程のシナプス形成とAMPA受容体GluR1サブユニットの動向2011

    • Author(s)
      浦久保知佳, 河合克宏, 小倉明彦, 冨永-吉野恵子
    • Organizer
      日本神経科学学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規スパインの形成は樹状突起のスパイン密度に依存する2011

    • Author(s)
      大江祐樹, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経科学学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 大脳皮質における海馬依存的な記憶固定のインビトロ再現の試み2011

    • Author(s)
      川上拓宏, 小倉明彦, 冨永-吉野恵子
    • Organizer
      日本神経化学会
    • Place of Presentation
      石川
    • Related Report
      2013 Final Research Report
  • [Presentation] 切片培養での長期シナプス増強におけるBDNF 放出の関与2011

    • Author(s)
      桜木繁雄, 冨永-吉野恵子, 小倉明彦
    • Organizer
      日本神経化学会
    • Place of Presentation
      石川
    • Related Report
      2013 Final Research Report
  • [Presentation] Dorsoventral bias of active neuronal population as an index of information transfer related to memory storage2011

    • Author(s)
      Nakamura, E., Ogura, A. Tominaga-Yoshino, K
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Final Research Report
  • [Presentation] Changes in gain and loss of dendritic spines after repeated LTP induction2011

    • Author(s)
      Oe, Y., Tominaga-Yoshino, K., Ogura, A
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット小脳顆粒細胞の生存に対する橋核の影響 : 代謝型グルタミン酸受容体の関与2011

    • Author(s)
      長谷川卓也, 森田大樹, 志賀千明, 冨永-吉野恵子, 小倉明彦
    • Organizer
      生理研研究会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Final Research Report
  • [Book] 記憶と夢の仮説. 近藤寿人編「芸術と脳」2013

    • Author(s)
      小倉明彦
    • Publisher
      大阪大学出版会
    • Related Report
      2013 Final Research Report
  • [Book] 芸術と脳(近藤寿人編)2013

    • Author(s)
      小倉明彦
    • Total Pages
      333
    • Publisher
      大阪大学出版会
    • Related Report
      2012 Annual Research Report
  • [Book] An in vitro model for analyzing the conversion of short-term to long-term memory, In "Short-Term Memory: New Research" Eds Kalivas, G. & Petralia, S. F.2012

    • Author(s)
      Tominaga-Yoshino, K. & Ogura, A
    • Publisher
      Nova Science Pub., New York
    • Related Report
      2013 Final Research Report
  • [Book] 記憶の細胞生物学2011

    • Author(s)
      小倉明彦, 冨永恵子
    • Publisher
      朝倉書店
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Book] An in vitro model for analyzing the conversion of short-term to long-term memory. In : Short-Term Memory : New Research. (Eds. Kalivas, G. & Petralia, S.F.)2011

    • Author(s)
      Tominaga-Yoshino, K., Ogura, A
    • Total Pages
      320
    • Publisher
      Noya Science Pub., New York
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.fbs.osaka-u.ac.jp/jp/seminar/21a.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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