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Learning-promoted synaptic diversity and a possible encording rule of CA1 pyramidal neurons

Research Project

Project/Area Number 19H03402
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionYamaguchi University

Principal Investigator

Mitsushima Dai  山口大学, 大学院医学系研究科, 教授 (70264603)

Co-Investigator(Kenkyū-buntansha) 西井 淳  山口大学, 大学院創成科学研究科, 教授 (00242040)
村井 礼  山口大学, 国際総合科学部, 准教授 (30279111)
石川 淳子  山口大学, 大学院医学系研究科, 助教 (30570808)
呉本 尭  日本工業大学, 先進工学部, 教授 (40294657)
崎本 裕也  山口大学, 大学院医学系研究科, 講師 (40634390)
木田 裕之  山口大学, 大学院医学系研究科, 講師 (70432739)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsエピソード学習 / AMPA受容体 / GABAA受容体 / super burst / ripple firings / synaptic diversity / memory encoding / entropy / エピソード記憶 / 海馬CA1 / リップル発火 / アセチルコリン / 学習・記憶 / シナプス可塑性 / リップル波 / 興奮性シナプス / 抑制性シナプス / decoding / neural code / AMPA receptor / GABAA receptor / episodic experience / contextual learning / self-entropy / 多ニューロン発火活動 / 海馬CA1ニューロン / 自己エントロピー / AI・深層学習 / AI機械学習
Outline of Research at the Start

ストレスを伴うエピソード経験は海馬内に強い記憶を形成し、個体は回避行動に役立てる。ラットを用いストレス回避学習を行うと、海馬CA1ニューロンに対する興奮性シナプスと抑制性シナプスの可塑性が高まり、多様な入力特性が保持されること、CA1ニューロン群により多様なリップル様同期発火活動が維持されることを発見した。本研究では、GABAA受容体β3 subunitのSer408-409リン酸化阻止実験を行い、シナプス・分子レベルの影響を解析し、学習との因果関係を引き続き立証する。さらに、経験前後や異経験間の違いをAI機械学習システムにより網羅的に比較分析し、学習の符号化ルール解明を目指す。

Outline of Final Research Achievements

We acclimated male rats to home cage and allowed them to experience one of the following episodes for 10 min: restraint stress, social contact with a female, social contact with a male, or contact with a novel object, and recorded multiple unit firing activity in the hippocampal CA1 neurons before and after in a freely moving condition. Forty minutes after the experience, the plasticity at excitatory and inhibitory synapses was analyzed using slice patch clamp technique. Although sporadic basal firings were mainly observed before the experience, spontaneous high-frequency firing over 3SD of basal firings occurred many times during and immediately after the experience, followed by numerous firing clusters (ripple firings, approx 50 msec duration). By analyzing the diversity, we found the diversity of spontaneous high-frequency firings, ripple firings, and synaptic diversification were specific to the most recent episodic experience.

Academic Significance and Societal Importance of the Research Achievements

記銘過程を明らかにできれば、認知症など高次機能疾患モデルと比較し、病態生理の解明や診断法の確立に生かせる。実際、Amyloid beta1-42 oligomerの海馬内投与は、エピソード学習を阻害し、閾値低下による異常発火やCA1シナプスにおけるGABAA受容体単一チャネル電流の低下など様々な病態変化を示した。どの段階でシナプスや発火活動に情報破綻が生じるのか疾患独自の障害発生源を特定し、薬物を用いた治療戦略に活用できると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 10 results) Remarks (4 results)

  • [Journal Article] A critical period for learning and plastic changes at hippocampal CA1 synapses2022

    • Author(s)
      Sakimoto Yuya、Shintani Ako、Yoshiura Daiki、Goshima Makoto、Kida Hiroyuki、Mitsushima Dai
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 7199-7199

    • DOI

      10.1038/s41598-022-10453-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diversity of learning-induced synaptic plasticity at dorsal CA1 synapses: a possible underlying mechanism of contextual memory formation2022

    • Author(s)
      Paw-Min-Thein-Oo、Sakimoto Yuya、Mitsushima Dai
    • Journal Title

      Medical Research Archives

      Volume: 10 Issue: 1 Pages: 1-12

    • DOI

      10.18103/mra.v10i1.2623

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of GABAA Receptor for Cognitive Function and Hippocampal Pathology2021

    • Author(s)
      Sakimoto Yuya、Paw Min-Thein-Oo、Goshima Makoto、Kanehisa Itsuki、Tsukada Yutaro、Mitsushima Dai
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 22 Pages: 12456-12456

    • DOI

      10.3390/ijms222212456

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Androgen affects the inhibitory avoidance memory by primarily acting on androgen receptor in the brain in adolescent male rats2021

    • Author(s)
      Md Nabiul Islam, Yuya Sakimoto, Mir Rubayet Jahan, Emi Miyasato, Abu Md Mamun Tarif, Kanako Nozaki, Koh-hei Masumoto, Akie Yanai, Dai Mitsushima, Koh Shinoda
    • Journal Title

      Brain Sciences

      Volume: 1(2) Issue: 2 Pages: 239-239

    • DOI

      10.3390/brainsci11020239

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hippocampal memory recognition using deep learning method2021

    • Author(s)
      Kuremoto T, Sasaki T, Ishikawa J, Mabu S, Mitsushima D.
    • Journal Title

      Internal Medicine Review

      Volume: 7 Issue: 1 Pages: 1-21

    • DOI

      10.18103/imr.v7i1.915

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Androgen Affects the Dynamics of Intrinsic Plasticity of Pyramidal Neurons in the CA1 Hippocampal Subfield in Adolescent Male Rats.2020

    • Author(s)
      Islam MN, Sakimoto Y, Jahan MR, Ishida M, Mamun Tarif AM, Nozaki K, Masumoto KH, Yanai A, Mitsushima D, Shinoda K.
    • Journal Title

      Neuroscience. 2020 May 23:S0306-4522(20)30319-5.

      Volume: 20 Pages: 15-29

    • DOI

      10.1016/j.neuroscience.2020.05.025

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proximodistal heterogeneity in learning-promoted pathway-specific plasticity at dorsal CA1 synapses.2020

    • Author(s)
      Paw-Min-Thein-Oo, Sakimoto Y, Kida H, Mitsushima D.
    • Journal Title

      Neuroscience

      Volume: 437 Pages: 184-194

    • DOI

      10.1016/j.neuroscience.2020.04.040

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the prefrontal cortex and basolateral amygdala to behavioral decision making under reward/punishment conflict2020

    • Author(s)
      Ishikawa, J., Sakurai, Y., Ishikawa, A. and Mitsushima, D.
    • Journal Title

      Psychopharmacology

      Volume: 237 Issue: 3 Pages: 639-654

    • DOI

      10.1007/s00213-019-05398-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A possible coding for experience: ripple-like events and synaptic diversity.2019

    • Author(s)
      Ishikawa J, Tomokage T, Mitsushima D.
    • Journal Title

      BioRxiv

      Volume: 12(30) Pages: 891259-891259

    • DOI

      10.1101/2019.12.30.891259

    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] Temporal dynamics of learning-promoted synaptic diversity in CA1 pyramidal neurons.2019

    • Author(s)
      Sakimoto Y, Kida H, Mitsushima D.
    • Journal Title

      FASEB J.

      Volume: 33(12) Issue: 12 Pages: 14382-14393

    • DOI

      10.1096/fj.201801893rrr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Remarks] 経験情報を符号化する海馬CA1リップル様発火活動:動的時間伸縮法を用いた網羅的類似解析

    • URL

      https://www.youtube.com/watch?v=rDqxQfDn4As

    • Related Report
      2021 Annual Research Report
  • [Remarks] Decoding of experience: DTW method for ripples

    • URL

      https://www.youtube.com/watch?v=Itq8nX8dmnA

    • Related Report
      2021 Annual Research Report
  • [Remarks] 海馬エピソード記憶の記銘過程(仮説)

    • URL

      https://www.youtube.com/watch?v=rDqxQfDn4As

    • Related Report
      2020 Annual Research Report
  • [Remarks] A hypothesis of early encoding process in CA1

    • URL

      https://www.youtube.com/watch?v=Itq8nX8dmnA

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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