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Role of activity-dependent gene Arc in synaptic plasticity

Research Project

Project/Area Number 24300117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neuroscience in general
Research InstitutionKyoto University (2013-2014)
The University of Tokyo (2012)

Principal Investigator

OKUNO Hiroyuki  京都大学, 医学(系)研究科(研究院), 特定准教授 (80272417)

Co-Investigator(Renkei-kenkyūsha) BITO Haruhiko  東京大学, 大学院医学系研究科, 教授 (00291964)
SAKIMURA Kenji  新潟大学, 脳研究所, 教授 (40162325)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Keywordsシナプス / 長期記憶 / 海馬 / Arc / CaMKII / 活動依存的遺伝子発現 / 可塑性 / 神経科学 / 脳・神経 / 遺伝子 / シグナル伝達
Outline of Final Research Achievements

Long-term synaptic plasticity and memory formation require activity-dependent gene expression. However, it remains unknown how such activity-induced gene products are targeted to proper cellular compartments including synapses. In the present study, we investigated the targeting of the memory related-protein Arc from the soma to the synapses, and elucidated a novel “inverse” synaptic tagging mechanism that enables Arc to specifically target the un-potentiated synapses. The findings provide new mechanistic insights into how the contrast between strong and weak synapses is maintained during long-term synaptic plasticity. We further identified the CREB coactivator CRTC1 as a critical factor for Arc expression as well as memory function.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (26 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Invited: 6 results) Book (4 results)

  • [Journal Article] Neuromodulatory effect of Gαs- or Gαq-coupled GPCR on NMDAR selectively activates the NMDAR/Ca2+/calcineurin/CREB-regulated transcriptional coactivator 1 (CRTC1) pathway to effectively induce Bdnf expression in neurons.2015

    • Author(s)
      Fukuchi M, Tabuchi A, Kuwana Y, Watanabe S, Inoue M, Takasaki I, Izumi H, Tanaka A, Inoue R, Mori H, Komatsu H, Takamori H, Okuno H, Bito H, Tsuda M.
    • Journal Title

      J Neurosci.

      Volume: 35 Issue: 14 Pages: 5606-5624

    • DOI

      10.1523/jneurosci.3650-14.2015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Class I histone deacetylase-mediated repression of the proximal promoter of the activity-regulated cytoskeleton-associated protein gene regulates its response to brain-derived neurotrophic factor.2015

    • Author(s)
      Fukuchi M, Nakashima F, Tabuchi A, Shimotori M, Tatsumi S, Okuno H, Bito H, Tsuda M
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 11 Pages: 6825-6836

    • DOI

      10.1074/jbc.m114.617258

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory2014

    • Author(s)
      Nonaka M, Kim R, Fukushima H, Sasaki K, Suzuki K, Okamura M, Ishii Y, Kawashima T, Kamijo S, Takemoto-Kimura S, Okuno H, Kida S, Bito H
    • Journal Title

      Neuron

      Volume: 84 Issue: 1 Pages: 92-106

    • DOI

      10.1016/j.neuron.2014.08.049

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Whole-brain mapping of behaviourally induced neural activation in mice.2014

    • Author(s)
      Vousden DA, Epp J, Okuno H, Nieman BJ, van Eede M, Dazai J, Ragan T, Bito H, Frankland PW, Lerch JP, Henkelman RM
    • Journal Title

      Brain Struct Funct.

      Volume: E-pub Issue: 4 Pages: 2043-2057

    • DOI

      10.1007/s00429-014-0774-0

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new era for functional labeling of neurons: activity-dependent promoters have come of age2014

    • Author(s)
      Kawashima T, Okuno H, Bito H
    • Journal Title

      Front. Neural Circuits

      Volume: 8 Pages: 37-37

    • DOI

      10.3389/fncir.2014.00037

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 核からシナプスへの分子ターゲティング機構の解明‐神経回路の長期可塑性を制御するArcタンパク質のケーススタディー2014

    • Author(s)
      奥野浩行、尾藤晴彦
    • Journal Title

      生化学

      Volume: 86 Pages: 18-27

    • NAID

      40020011052

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE2013

    • Author(s)
      Kawashima T, Kitamura K, Suzuki K, Nonaka M, Kamijo S, Takemoto-Kimura S, Kano M, Okuno H, Ohki K, Bito H.
    • Journal Title

      Nature Methods

      Volume: 10 Issue: 9 Pages: 889

    • DOI

      10.1038/nmeth.2559

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arc/Arg3.1 Is a Postsynaptic Mediator of Activity-Dependent Synapse Elimination in the Developing Cerebellum2013

    • Author(s)
      Mikuni et al.
    • Journal Title

      Neuron

      Volume: 78 Issue: 6 Pages: 1024

    • DOI

      10.1016/j.neuron.2013.04.036

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonlinear Decoding and Asymmetric Representation of Neuronal Input Information by CaMKIIα and Calcineurin2013

    • Author(s)
      Fujii H, Inoue M, Okuno H, Sano Y; Takemoto-Kimura S, Kitamura K, Kano M, Bito H.
    • Journal Title

      Cell Reports

      Volume: 3 Issue: 4 Pages: 978

    • DOI

      10.1016/j.celrep.2013.03.033

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Untangling the two-way signalling route from synapses to the nucleus, and from the nucleus back to the synapses.2013

    • Author(s)
      Nonaka et al.
    • Journal Title

      Philos Trans R Soc Lond B Biol Sci.

      Volume: 369 Issue: 1633 Pages: 20130150-20130150

    • DOI

      10.1098/rstb.2013.0150

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKllβ2012

    • Author(s)
      奥野浩行, 他
    • Journal Title

      Cell

      Volume: 149 Issue: 4 Pages: 886-898

    • DOI

      10.1016/j.cell.2012.02.062

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of the cortical projection neurons by retrograde TET-OFF lentiviral vector.2012

    • Author(s)
      渡我部昭哉, 他
    • Journal Title

      PLos One

      Volume: 7 Issue: 10 Pages: e46157-e46157

    • DOI

      10.1371/journal.pone.0046157

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation2012

    • Author(s)
      Endo T, Kakeyama M, Uemura Y, Haijima A, Okuno H, Bito H, Tohyama C
    • Journal Title

      PLOS ONE

      Volume: 7 Issue: 12 Pages: e50741-e50741

    • DOI

      10.1371/journal.pone.0050741

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 神経特異的前初期遺伝子Arcによる認知機能調節2014

    • Author(s)
      奥野 浩行
    • Organizer
      包括脳2014冬のシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-12-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulation of synaptic and cognitive function through the activity-dependent gene Arc/Arg3.1.2014

    • Author(s)
      Okuno, H., Endo, T., Kim, R., Ishii, Y., Minatohara, K., Araki, A., Sakimura, K., Bito, H.
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学学会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Arc's roles in inverse synaptic tagging and memory formation.2014

    • Author(s)
      Okuno, H., Minatohara, K., Masuda, H.
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Inverse synaptic tagging : a new mechanism for late-phase synaptic plasticity.2012

    • Author(s)
      Okuno H, Ishii Y, Kawashima T, Nonaka M, Akashi K, Sakimura K, Bito H.
    • Organizer
      第35回日本分子生物年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡市)
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Visualization of an active ensemble of cortical neurons in vivo using a novel activity-dependent promoter E-SARE.2012

    • Author(s)
      Kawashimna T, Kitamura K, Ohki K, Suzuki K, Nonaka M, Kamijo S, Takemoto-Kimura S, Kano M, Okuno H, Bito H.
    • Organizer
      42th Annual Meeting of Soc for Neurosci,
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2012-10-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Possible involvement of the Ca2+-dependent gene Arc in activity dependent synapse elimination in the cerebellum.2012

    • Author(s)
      Mikuni T, Uesaka N, Okuno H, Hirai H, Bito H, Kano M
    • Organizer
      42th Annual Meeting of Soc for Neurosci
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2012-10-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] The role of Arc in inverse tagging of inactive synapses

    • Author(s)
      Okuno, H
    • Organizer
      International Society for Neurochemistry (ISN2013)
    • Place of Presentation
      Cancun, Mexico
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of synaptic strength byArc/Arg3.1-CaMKIIbeta interaction through inverse tagging process

    • Author(s)
      Okuno, H
    • Organizer
      Korean Physiology Society (KPS 2013)
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Ca2+/カルモジュリン依存性キナーゼIIβとArcによるAMPA型グルタミン酸受容体の量的制御

    • Author(s)
      奥野浩行、石井雄一郎、川島尚之、野中美応、明石馨、崎村建司、尾藤晴彦
    • Organizer
      第36回日本分子生物年会
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] Neuroplasticity in "Homeostatic control of brain function” eds., Masino, SA. & Boison,2015

    • Author(s)
      Okuno, H.
    • Publisher
      Oxford University Press
    • Related Report
      2014 Annual Research Report
  • [Book] Inverse synaptic tagging by Arc. in "Novel Mechanisms of Memory" eds., Giese, K.P. & Radwanska, K.,2015

    • Author(s)
      Okuno, H., Araki, A., Minatohara, K.
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Selected key areas for future research on the claustrum. in “The Claustrum” eds., Smythies., Edelstein L., & Ramachandran, V.S.2014

    • Author(s)
      Okuno, H., Smythies, J., Edelstein L.
    • Total Pages
      13
    • Publisher
      Elsevier
    • Related Report
      2014 Annual Research Report
  • [Book] Chapter "Selected key areas for future research on the claustrum" in The Claustrum2013

    • Author(s)
      Okuno, Smythies and Edelstein
    • Publisher
      Academia Press
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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