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Molecular basis for memory decifits with abnormalities in synaptic morphology and circuit dynamics

Research Project

Project/Area Number 18H02536
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

YAMAGATA Kanato  公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 研究員 (20263262)

Co-Investigator(Kenkyū-buntansha) 田中 秀和  立命館大学, 生命科学部, 教授 (70273638)
平井 志伸  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (00625189)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords結節性硬化症 / 記憶痕跡細胞
Outline of Final Research Achievements

It is known that the shape of synapses changes during memory formation, but there is no evidence that synaptic abnormalities cause memory impairments. In this study, we focused on tuberous sclerosis (TSC) as a disease that causes memory impairments and compared memory trace cells involved in memory between wild-type and TSC model mice. As a result, we found that there were fewer active trace cells and less synaptic changes during memory recall in TSC model mice. Therefore, we administered a therapeutic candidate to the model mice, which resulted in an improvement in the activity of trace cells, synaptic morphology, and memory recovery. From these results, we suggest that synaptic morphological abnormalities can cause improper functioning of memory circuits and lead to memory impairments.

Academic Significance and Societal Importance of the Research Achievements

脳の高次機能、特に記憶の形成にシナプスの形態変化を伴うことは、自明の理となっている。しかし、記憶の異常を伴う病気や疾患モデルにおいて、シナプスの形態異常が記憶障害を起こすという直接の証拠は未だ示されていない。本研究では、記憶障害を示す疾患として結節性硬化症を取り上げ、そのモデルマウスを使用して、遺伝学的・薬理学的なシナプス形態・回路動態の改善が記憶の回復に寄与するかどうかを検証したい。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Johns Hopkins University(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Spine morphogenesis and synapse formation in tubular sclerosis complex models2022

    • Author(s)
      Shimada Tadayuki、Yamagata Kanato
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 15 Pages: 1019343-1019343

    • DOI

      10.3389/fnmol.2022.1019343

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Farnesyltransferase Inhibitor Restores Cognitive Deficits in Tsc2 +/- Mice through Inhibition of Rheb12022

    • Author(s)
      Sugiura H, Shimada T, Moriya-Ito K, Goto JI, Fujiwara H, Ishii R, Shitara H, Taya C, Fujii S, Kobayashi T, Hino O, Worley PF, Yamagata K
    • Journal Title

      J Neurosci

      Volume: 42 Issue: 12 Pages: 2598-2612

    • DOI

      10.1523/jneurosci.0449-21.2022

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tuberous Sclerosis Complex (TSC) Inactivation Increases Neuronal Network Activity by Enhancing Ca 2+ Influx via L-Type Ca 2+ Channels2021

    • Author(s)
      Hisatsune C, Shimada T, Miyamoto A, Lee A, Yamagata K
    • Journal Title

      J Neurosci

      Volume: 41 Issue: 39 Pages: 8134-8149

    • DOI

      10.1523/jneurosci.1930-20.2021

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] てんかんの難治化因子neuritin2021

    • Author(s)
      島田 忠之、山形 要人
    • Journal Title

      Clinical Neuroscience

      Volume: 42 Pages: 1588-1590

    • Related Report
      2021 Annual Research Report
  • [Journal Article] てんかんの難治化因子neuritin2021

    • Author(s)
      島田忠之、山形要人
    • Journal Title

      Clinical Neuroscience.

      Volume: 39 Pages: 1588-1590

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Serotonin induces Arcadlin in hippocampal neurons2020

    • Author(s)
      Tanaka Hidekazu、Sawano Toshinori、Konishi Naoko、Harada Risako、Takeuchi Chiaki、Shin Yuki、Sugiura Hiroko、Nakatani Jin、Fujimoto Takahiro、Yamagata Kanato
    • Journal Title

      Neuroscience Letters

      Volume: 721 Pages: 134783-134783

    • DOI

      10.1016/j.neulet.2020.134783

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Syntenin: PDZ Protein Regulating Signaling Pathways and Cellular Functions2019

    • Author(s)
      Tadayuki Shimada, Shin Yasuda, Hiroko Sugiura, and Kanato Yamagata.
    • Journal Title

      International Journal of Molecular Science

      Volume: 20(17) Issue: 17 Pages: 4171-4171

    • DOI

      10.3390/ijms20174171

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening of new therapeutic compounds for tuberous sclerosis complex.2019

    • Author(s)
      Yamagata K, Shimada T, Suigura H
    • Journal Title

      Ann. Rep. Jon. Epi. Res. Found.

      Volume: 30 Pages: 57-64

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Pentylenetetrazole-Induced Kindling Mouse Model.2018

    • Author(s)
      Shimada T, Yamagata K.
    • Journal Title

      Journal of Visualized Experiments

      Volume: 12 Issue: 136 Pages: 136-136

    • DOI

      10.3791/56573

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of neuritin in retinal ganglion cell death in adult mice following optic nerve injury.2018

    • Author(s)
      Azuchi Y, Namekata K, Shimada T, Guo X, Kimura A, Harada C, Saito A, Yamagata K, Harada T.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 10132-10132

    • DOI

      10.1038/s41598-018-28425-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 自閉症におけるシナプス異常の新知見2018

    • Author(s)
      山形要人、島田忠之、杉浦弘子
    • Journal Title

      細胞

      Volume: 50 Pages: 17-20

    • Related Report
      2018 Annual Research Report
  • [Presentation] Reactive astrocyte-mediated mechanisms of memory disorder in tubular sclerosis complex model mouse2022

    • Author(s)
      Tadayuki Shimada, Hiroko Sugiura, and Kanato Yamagata
    • Organizer
      Neuro2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reactive astrocyte-mediated memory disorder in tubular sclerosis complex model2021

    • Author(s)
      Tadayuki Shimada, Hiroko Sugiura, and Kanato Yamagata
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Reactive astrocyte-mediated memory disorder in tubular sclerosis complex model mouse2021

    • Author(s)
      Tadayuki Shimada, Hiroko Sugiura, and Kanato Yamagata
    • Organizer
      第64回日本神経化学会大会,
    • Related Report
      2020 Annual Research Report
  • [Presentation] TMiMS Synaptic Plasticity Project.2019

    • Author(s)
      Yamagata K.
    • Organizer
      21st TMIMS International Symposium “Overcoming neuropsychopharmacology crisis”.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Inhibition of Rheb improved abnormal social behavior in astrocyte-specific Tsc1 knockout mice.2019

    • Author(s)
      Shimada T, Sugiura H, Yamagata K.
    • Organizer
      62nd Annual Meeting of the Japanese Society for Neurochemistry.
    • Related Report
      2019 Annual Research Report
  • [Presentation] Insufficient establishment of memory engram cells may cause contextual memory impairment in a mouse model of tuberous sclerosis complex.2019

    • Author(s)
      Moriya-Ito K, Shimada T, Sugiura H, Yamagata K.
    • Organizer
      62nd Annual Meeting of the Japanese Society for Neurochemistry
    • Related Report
      2019 Annual Research Report
  • [Presentation] Inhibition of Rheb improved avnormal social behavior in astrocyte-specific Tsc1 knockout mice.2019

    • Author(s)
      Shimada T, Sugiura H, Yamagata K.
    • Organizer
      20th TMIMS International Symposium ”Principles of Neocortical Development and Evolution”.
    • Related Report
      2019 Annual Research Report
  • [Presentation] TSC2欠損型ヒトiPS細胞由来の神経細胞にみられる神経ネットワーク異常2019

    • Author(s)
      久恒智博、島田忠之、山形要人
    • Organizer
      第42回 日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Rheb inhibitors restore cognitive deficits in a mouse model of tuberous sclerosis complex.2018

    • Author(s)
      Yamagata K, Sugiura H, Shimada T, Goto JI, Fujiwara H, Yasuda S, Kobayashi T, Hino O, Fujii S and Worley PF.
    • Organizer
      International Tuberous Sclerosis Complex Research Conference 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Memory impairment in astrocyte-specific Tsc1 knockout mice was recovered by Rheb inhibition.2018

    • Author(s)
      Shimada T, Sugiura H, Yamagata K
    • Organizer
      22nd Biennial Meeting of the International Society for Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 結節性硬化症モデルマウスにおける記憶障害と歯状回顆粒細胞の活動異常2018

    • Author(s)
      守屋敬子 島田忠之 杉浦弘子 山形要人
    • Organizer
      第27回海馬と高次脳機能学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanism of memory impairment in astrocyte specific Tsc1 knockout mouse.2018

    • Author(s)
      Shimada T, Sugiura H, Yamagata K
    • Organizer
      61st Annual Meeting of the Japanese Society for Neurochemistry.
    • Related Report
      2018 Annual Research Report
  • [Presentation] A new model of attention-deficit/hyperactivity disorder (ADHD) related with Arcadlin2018

    • Author(s)
      Takemiya T, Kawakami M, Yamagata K, Yasuda S, Izumi K
    • Organizer
      61st Annual Meeting of the Japanese Society for Neurochemistry
    • Related Report
      2018 Annual Research Report
  • [Book] Encyclopedia of Signaling Molecules2018

    • Author(s)
      Sangdun Choi
    • Total Pages
      6330
    • Publisher
      Springer
    • ISBN
      1493967991
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京都医学総合研究所こどもの脳プロジェクト

    • URL

      https://www.igakuken.or.jp/project/detail/development.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 公益財団法人東京都医学総合研究所 シナプス可塑性プロジェクト

    • URL

      http://www.igakuken.or.jp/project/detail/plasticity.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] http://www.igakuken.or.jp

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 知的障害又は自閉症治療薬2018

    • Inventor(s)
      山形要人 島田忠之 杉浦弘子 安田新
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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