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Formation mechanism and functional role of place cell ensemble related to reward-associated memory

Research Project

Project/Area Number 19K16293
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionKyoto University

Principal Investigator

Kotaro Mizuta  京都大学, 医学研究科, 助教 (60632891)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords報酬 / 記憶 / バーチャルリアリティ / 二光子イメージング / 場所細胞 / 海馬 / バーチャルリアリティー / in vivoイメージング / 記憶・学習
Outline of Research at the Start

動物がある空間を探索するとき、空間上の重要な場所がどのように表現され、記憶として保持されるかはわかっていない。申請者は、報酬周辺には場所特異的な活動を示す場所細胞が集積すること(報酬場所細胞)を見出し、通常の場所細胞は数日単位で場所特異性が変化していくのに対し、報酬場所細胞は、毎日同じ場所で安定して発火し続け、新たな形質を持つ細胞群であることがわかった。そこで、本研究では、報酬場所細胞が既存の場所細胞からどのように形成されるか、報酬そのものを認識しているのか、あるいは場所との組み合わせが重要なのか、さらに記憶の痕跡に関連するのか、その形成に報酬系が如何に関係しているかを解明していく。

Outline of Final Research Achievements

Place cells around reward in the hippocampus are more numerous and stable than in other locations, and we named them “reward place cells”. We aimed to elucidate functional role and formation mechanism of reward place cells. For the purpose, we visualized hippocampal neural activity in mice navigating virtual reality linear track tasks using two-photon microscopy. If the reward location could not be identified by changing randomly every trial, over-representation of reward place cells was not observed. Next, mice performed a delayed task in which the reward was given if mouse stay at the reward location for 2 seconds. A subset of reward place cells was active during stopping in the reward location. Thus, reward place cells were either associated with anticipation of reward or with recognition of the reward location. We found that the reward relocations cause the rapid formation of reward place cells by reorganization from existing cognitive maps, unlike novel learning.

Academic Significance and Societal Importance of the Research Achievements

探索経路の記憶には静止時に場所細胞群が高速で発火するreplay現象が関与するが、探索経路で報酬のような重要な目的地が場所細胞やその他の細胞によってどのように表現され記憶されるかわかっていなかった。本研究で明らかになった報酬の周辺の場所細胞や報酬事象を示す細胞の特性、それらの活動およびダイナミクスなどの知見は、行動に関連する海馬の神経回路ダイナミクスやシナプス可塑性、および、アルツハイマー病のような記憶研究に関わる病態モデル、人工知能研究などの多くの研究分野に大きなインパクトをもたらすことが期待される。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 Other

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

  • [Int'l Joint Research] マックスプランク研究所(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] カハール研究所(スペイン)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Multiple coordinated cellular dynamics mediate CA1 map plasticity2021

    • Author(s)
      Mizuta Kotaro、Nakai Junichi、Hayashi Yasunori、Sato Masaaki
    • Journal Title

      Hippocampus

      Volume: 31 Issue: 3 Pages: 235-243

    • DOI

      10.1002/hipo.23300

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two functionally distinct serotonergic projections into hippocampus2020

    • Author(s)
      Luchetti Alessandro、Bota Ayaka、Weitemier Adam、Mizuta Kotaro、Sato Masaaki、Islam Tanvir、McHugh Thomas J.、Tashiro Ayumu、Hayashi Yasunori
    • Journal Title

      The Journal of Neuroscience

      Volume: - Issue: 25 Pages: 4936-4944

    • DOI

      10.1523/jneurosci.2724-19.2020

    • NAID

      120006893992

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus2020

    • Author(s)
      Masaaki Sato, Kotaro Mizuta, Tanvir Islam, Masako Kawano, Yukiko Sekine, Takashi Takekawa, Daniel Gomez-Dominguez, Alexander Schmidt, Fred Wolf, Karam Kim, Hiroshi Yamakawa, Masamichi Ohkura, Min Goo Lee, Tomoki Fukai, Junichi Nakai, Yasunori Hayashi
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 1 Pages: 107864-107864

    • DOI

      10.1016/j.celrep.2020.107864

    • NAID

      120006867158

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Amyloid-β-Dependent Neuronal Circuit Rearrangement in Presymptomatic Alzheimer’s Disease2019

    • Author(s)
      Mizuta Kotaro、Saneyoshi Takeo
    • Journal Title

      Biological Psychiatry

      Volume: 86 Issue: 3 Pages: 167-168

    • DOI

      10.1016/j.biopsych.2019.06.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Nonspatiotemporal-encoding hyperactivity is elevated in the hippocampal CA1 region of Alzheimer’s disease model mice2020

    • Author(s)
      Risa Takamura, Kotaro Mizuta, Yukiko Sekine, Tanvir Islam, Takashi Saito, Takashi Takekawa, Masamichi Ohkura, Tomoki Fukai, Junichi Nakai, Toshio Ohshima, Takaomi Saido, Yasunori Hayashi
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Distinct projection of anterior cingulate cortex layer 2/3 and 5 neurons2020

    • Author(s)
      李耀龍、水田恒太郎、林康紀
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 海馬CA1における空間と事象表現の同期活動2020

    • Author(s)
      水田恒太郎、佐藤正晃、関根友紀子、河野真子、イスラムタンビル、李耀龍、竹川高志、大倉正道、中井淳一、林康紀
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Hippocampal place- and time-encoding cells have different vulnerability in Alzheimer’s disease model mice.2019

    • Author(s)
      Risa Takamura, Kotaro Mizuta, Yukiko Sekine, Tanvir Islam, Takashi Saito, Takashi Takekawa, Masamichi Ohkura, Tomoki Fukai, Junichi Nakai, Takaomi C. Saido, Yasunori Hayashi
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Remarks] 脳内地図を細胞レベルで観察

    • URL

      https://www.riken.jp/press/2020/20200708_1/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 脳内地図を細胞レベルで観察 -自閉症関連遺伝子Shank2はランドマーク情報に必須-

    • URL

      https://www.kyoto-u.ac.jp/ja/research-news/2020-07-09-1

    • Related Report
      2020 Annual Research Report
  • [Remarks] 知の京都- 水田恒太郎さん(京都大学医学研究科システム神経薬理学 助教)

    • URL

      https://www.pref.kyoto.jp/sangyo-sien/specialist/mizutakotaro.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 林康紀研究室ホームページ

    • URL

      http://glutamate.med.kyoto-u.ac.jp/

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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