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Neuronal mechanisms underlying synaptic and behavioral plasticity regulated by dopamine

Research Project

Project/Area Number 20K15936
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Nagase Masashi  東京慈恵会医科大学, 医学部, 助教 (40749462)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords扁桃体 / 腹側被蓋野 / 腕傍核 / シナプス可塑性 / ドーパミン
Outline of Research at the Start

恐怖などの負情動は危険を知らせる警告信号としての役割を担う一方、負情動の制御破綻は過度の苦痛をもたらし大きな問題となる。申請者らは、脳幹から情動の座である扁桃体への投射が強い恐怖情動によってシナプス増強を示すことを明らかにした。本研究では、脳幹‐扁桃体回路の修飾因子としてドーパミンに着目し、ドーパミン神経の主要な起始核である腹側被蓋野との神経回路を、光遺伝学、電気生理学、行動学的手法を用いて包括的に解析し、その生理的意義とシナプス・回路レベルでの制御機構を明らかにすることを目指す。

Outline of Final Research Achievements

While negative emotion, such as fear and pain, serves as an alarm signal of danger, dysregulation of the negative emotion is a critical clinical issue. However, neural circuitry mechanisms of regulation of negative emotion, in particular those mediated by neuromodulators, remain unknown. This study focused on dopamine and analyzed roles of a brainstem-midbrain-amygdala circuit to elucidate its physiological significance. We found modulation of mouse behavior by the activation of brainstem-midbrain pathway, induction of avoidance behavior by the activation of brainstem-amygdala pathway, modulatory effects of dopamine on the synaptic transmission in brainstem-amygdala pathway, and experience-dependent changes in taste preferences accompanied by plastic changes in the brainstem-midbrain-amygdala circuit.

Academic Significance and Societal Importance of the Research Achievements

PTSDなどの精神疾患や慢性疼痛に伴う負情動の制御破綻は過度の苦痛をもたらし、QOLを著しく低下させて臨床上の大きな問題となるが、治療法が乏しいのが現状である。本研究では脳幹-腹側被蓋野-扁桃体神経回路による情動関連行動の制御や味覚情動価の変容に伴う可塑的変化、ドーパミンによる回路修飾を見出した。これらの結果は、負情動の制御破綻を伴う疾患に対して、脳幹-腹側被蓋野-扁桃体神経回路が治療標的となりうることを示すとともに、ドーパミン受容体を標的とする既存の薬物を用いた新たな治療戦略の開発に繋がることが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results)

  • [Journal Article] Experience-dependent changes in affective valence of taste in male mice2023

    • Author(s)
      Hamada Shun、Mikami Kaori、Ueda Shuhei、Nagase Masashi、Nagashima Takashi、Yamamoto Mikiyasu、Bito Haruhiko、Takemoto-Kimura Sayaka、Ohtsuka Toshihisa、Watabe Ayako M.
    • Journal Title

      Molecular Brain

      Volume: 16 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s13041-023-01017-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice2022

    • Author(s)
      Nagashima Takashi、Tohyama Suguru、Mikami Kaori、Nagase Masashi、Morishima Mieko、Kasai Atsushi、Hashimoto Hitoshi、Watabe Ayako M.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41467-022-35634-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The parabrachial-to-amygdala pathway provides aversive information to induce avoidance behavior in mice2021

    • Author(s)
      Ito Mariko、Nagase Masashi、Tohyama Suguru、Mikami Kaori、Kato Fusao、Watabe Ayako M.
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 94-94

    • DOI

      10.1186/s13041-021-00807-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An engineered channelrhodopsin optimized for axon terminal activation and circuit mapping2021

    • Author(s)
      Hamada Shun、Nagase Masashi、Yoshizawa Tomohiko、Hagiwara Akari、Isomura Yoshikazu、Watabe Ayako M.、Ohtsuka Toshihisa
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s42003-021-01977-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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