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Integrated modeling of synaptic plasticity for associative emotional learning

Research Project

Project/Area Number 17K00404
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Life / Health / Medical informatics
Research InstitutionNational Institute for Physiological Sciences (2020)
Kyoto University (2017-2019)

Principal Investigator

Urakubo Hidetoshi  生理学研究所, 脳機能・計測支援センター 電子顕微鏡室, 特任助教 (40512140)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords中型有棘細胞 / ドーパミン / シナプス可塑性 / シグナル伝達モデル / シミュレーション / 計算論的神経科学 / FIB/SEM / 強化学習 / コンピュータシミュレーション / シグナル伝達
Outline of Final Research Achievements

Conjunctive signals of Dopamine (DA) and Glutamate (Glu) induce synaptic plasticity in the striatum. We here developed computational models of signaling dynamics for the synaptic plasticity, in particular, the signaling dynamics dependent on DA D2 receptors (D2R). Model analyses revealed that the expression levels of two types of molecules (D2R and “regulator of G-proteins (RGS)”) need to be balanced for the synaptic plasticity, and their imbalanced states correspond to those in psychiatric disorders. We also conducted reaction-diffusion simulation of Ca2+ dynamics within morphologically realistic spines that were obtained from electron microscopic images.

Academic Significance and Societal Importance of the Research Achievements

D2モデルにおいて、DA dipシグナルが正しく検出されてAC1活性が生じるパラメータの検討から、ドーパミンD2受容体とRGS二種類の分子の発現量のバランスの崩れと、統合失調症およびDYT1ジスキネジアの二つの精神疾患を対応づけることができた。特にDYT1ジスキネジアの疾患メカニズムの理解と治療法の開発への発展が期待される。
また、電子顕微鏡画像からスパイン形状を抽出してシグナル伝達の時空間シミュレーションを行う技術は、細胞内シグナル伝達研究の分野において広範な応用が期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (9 results) (of which Invited: 5 results) Remarks (3 results)

  • [Int'l Joint Research] University Leipzig(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Information Technologies for 3D Reconstruction of Neuronal Circuits Based on Volumetric Electron Microscopic Images2020

    • Author(s)
      浦久保秀俊、窪田芳之
    • Journal Title

      KENBIKYO

      Volume: 55 Issue: 3 Pages: 120-124

    • DOI

      10.11410/kenbikyo.55.3_120

    • NAID

      130007967720

    • ISSN
      1349-0958, 2434-2386
    • Year and Date
      2020-12-30
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling models for dopamine-dependent temporal contiguity in striatal synaptic plasticity2020

    • Author(s)
      Hidetoshi Urakubo, Sho Yagishita, Haruo Kasai, Shin Ishii
    • Journal Title

      PLoS Computational Biology

      Volume: 16 Issue: 7 Pages: 1008078-1008078

    • DOI

      10.1371/journal.pcbi.1008078

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Geometry and the Organizational Principle of Spine Synapses along a Dendrite2020

    • Author(s)
      Parajuli Laxmi Kumar、Urakubo Hidetoshi、Takahashi-Nakazato Ai、Ogelman Roberto、Iwasaki Hirohide、Koike Masato、Kwon Hyung-Bae、Ishii Shin、Oh Won Chan、Fukazawa Yugo、Okabe Shigeo
    • Journal Title

      eneuro

      Volume: 7 Issue: 6 Pages: 0248-20

    • DOI

      10.1523/eneuro.0248-20.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generative and discriminative model-based approaches to microscopic image restoration and segmentation2020

    • Author(s)
      Ishii Shin、Lee Sehyung、Urakubo Hidetoshi、Kume Hideaki、Kasai Haruo
    • Journal Title

      Microscopy

      Volume: 69 Issue: 2 Pages: 79-91

    • DOI

      10.1093/jmicro/dfaa007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mu-net: Multi-scale U-net for two-photon microscopy image denoising and restoration2020

    • Author(s)
      Lee Sehyung、Negishi Makiko、Urakubo Hidetoshi、Kasai Haruo、Ishii Shin
    • Journal Title

      Neural Networks

      Volume: 125 Pages: 92-103

    • DOI

      10.1016/j.neunet.2020.01.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] UNI-EM: An Environment for Deep Neural Network-Based Automated Segmentation of Neuronal Electron Microscopic Images2019

    • Author(s)
      Urakubo Hidetoshi、Bullmann Torsten、Kubota Yoshiyuki、Oba Shigeyuki、Ishii Shin
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19413-19413

    • DOI

      10.1038/s41598-019-55431-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABAergic inhibition reduces the impact of synaptic excitation on somatic excitation2018

    • Author(s)
      Kobayashi Chiaki、Okamoto Kazuki、Mochizuki Yasuhiro、Urakubo Hidetoshi、Funayama Kenta、Ishikawa Tomoe、Kashima Tetsuhiko、Ouchi Ayako、Szymanska Agnieszka F.、Ishii Shin、Ikegaya Yuji
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 00-00

    • DOI

      10.1016/j.neures.2018.09.014

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Simulation of spatiotemporal signaling dynamics for synaptic plasticity using technologies for EM connectomics2021

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      第126回 日本解剖学会総会・全国学術集会 | 第98回 日本生理学会大会 合同大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Simulation of Ca2+ dynamics within morphologically realistic neuronal spines2021

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      The 2nd CIBoG (Convolution of Informatics and Biomedical Sciences) Retreat
    • Related Report
      2020 Annual Research Report
  • [Presentation] シナプス可塑性のシグナル伝達からEMコネクトミクスへ:拡大するコンピュテーションの役割2020

    • Author(s)
      浦久保秀俊
    • Organizer
      自然科学研究機構・生理学研究所・部門公開セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 二次元EM スタック画像からの自動3D 再構築2020

    • Author(s)
      浦久保秀俊
    • Organizer
      日本生理学会・企画シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Google Cloudを用いた神経組織SEM連続断面データの解析例の実際2019

    • Author(s)
      窪田芳之、浦久保秀俊
    • Organizer
      日本顕微鏡学会「生体ボリュームイメージング研究会第3回研究会」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Automated 3D reconstruction from a 2D stack of neuronal EM images2018

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      日本顕微鏡学会 第74回学術講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Improvement of a proof reading software in EM connectomics and its application to the simulation of extracellular DA signaling2018

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      第10回光操作研究会・第2回脳情報動態 合同国際シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Multi-label volume reconstruction of FIB/SEM images and its application to the simulation of extracellular DA signaling2018

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of a unified environment for automated neuronal network reconstruction from EM images2018

    • Author(s)
      Hidetoshi Urakubo
    • Organizer
      Advances in neuroinformatics (AINI2018
    • Related Report
      2018 Research-status Report
  • [Remarks] UNI-EM

    • URL

      https://github.com/urakubo/UNI-EM.git

    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      https://github.com/urakubo/UNI-EM

    • Related Report
      2019 Research-status Report
  • [Remarks] DNNを用いた神経EM画像セグメンテーションのための統合環境

    • URL

      https://github.com/urakubo/UNI-EM

    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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