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Axon initial segment plasticity in the jumping escape giant fiber neuron

Research Project

Project/Area Number 19KK0383
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

Allocation TypeMulti-year Fund
Research Field Basic / Social brain science
Research InstitutionAkita University (2023)
Tohoku University (2019-2022)

Principal Investigator

Yamagata Nobuhiro  秋田大学, 理工学研究科, 准教授 (50716248)

Project Period (FY) 2020 – 2023
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Keywords軸索起始部 / ドーパミン受容体 / 活動電位 / ドーパミン / 神経可塑性 / ショウジョウバエ / イオンチャネル
Outline of Research at the Start

軸索起始部(AIS)は、活動電位の発生部位として神経出力の決定に関わり、正常かつ可塑的な神経活動に必須である。その制御メカニズムを理解するため、AISにおけるドーパミン受容体の一種、DopEcRの作用機序を分子レベルで明らかにすることが本事業の目的である。そのためチャネルレベルのイオン電流の解析を可能とするパッチクランプ法を習得し、薬理学、遺伝学的手法と組み合わせ、活動電位の発生制御におけるDopEcRの機能を明らかにする。特に当該分子の活性に伴う局所イオン流の変化、関連するイオンチャネルを明らかにし、ドーパミンを介した活動電位制御、さらには細胞下レベルの神経可塑性メカニズムの理解に貢献する。

Outline of Final Research Achievements

In the research project, I examined the axon initial segment (AIS) and its role in neural output regulation and neural plasticity. One specific area of focus was the DopEcR, a dopamine receptor located in the AIS. Through molecular localization in a multinuclear neuroblast culture system, we found that DopEcR and NaV are co-localized in the AIS. Furthermore, experiments measuring the DLM flight muscle, which is part of the giant escape system, demonstrated the involvement of DopEcR, cAMP, and TRPV in promoting stimulus habituation. This suggests that DopEcR has an inhibitory effect on action potential generation through specific ion channels in the AIS. These findings provide valuable insights into the molecular basis of AIS plasticity and its potential implications for neurological and psychiatric disorders.

Academic Significance and Societal Importance of the Research Achievements

中枢神経系の馴化における個別のチャネル遺伝子の機能理解に繋がり、AISの制御メカニズムを含む神経可塑性の基礎的メカニズムの理解に貢献する。
ドーパミン受容体のアゴニスト、アンタゴニストは、さまざまな精神疾患の処方薬として多く用いられているが、副作用も多い。より安全かつ効果の高い新薬の開発のためにも、ドーパミン受容体の「細胞内効果」の十分な理解が必要である。本課題では、DopEcRの標的チャネルからその細胞内効果を分子レベルで特定し、これに貢献することを目指す。同方法論は、さまざまな分子機能の解析にも適用でき、異なる受容体を介したドーパミン作用の機能解析も加速できるものと期待している。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Open Access: 4 results,  Peer Reviewed: 4 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Int'l Joint Research] The University of Iowa(米国)2021

    • Year and Date
      2021-05-06
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Cell-type-specific fluorescent tagging of endogenous target proteins reveals synaptic enrichment and dynamic regulations of dopamine receptors2024

    • Author(s)
      Hiramatsu Shun、Saito Kokoro、Kondo Shu、Katow Hidetaka、Yamagata Nobuhiro、Wu Chun-Fang、Tanimoto Hiromu
    • Journal Title

      bioRxiv

      Volume: 1 Pages: 1-32

    • DOI

      10.1101/2024.04.29.591637

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Editorial overview: Aroma nudges in bugs: Sensory perception and memory in insects2024

    • Author(s)
      Mizunami Makoto、Yamagata Nobuhiro
    • Journal Title

      Current Opinion in Insect Science

      Volume: 62 Pages: 101165-101165

    • DOI

      10.1016/j.cois.2024.101165

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory2022

    • Author(s)
      Yamagata Nobuhiro、Imanishi Yasuhito、Wu Hongyang、Kondo Shu、Sano Hiroko、Tanimoto Hiromu
    • Journal Title

      Frontiers in Behavioral Neuroscience

      Volume: 16 Pages: 986064-986064

    • DOI

      10.3389/fnbeh.2022.986064

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Presynaptic inhibition of dopamine neurons controls optimistic bias2021

    • Author(s)
      Yamagata Nobuhiro、Ezaki Takahiro、Takahashi Takahiro、Wu Hongyang、Tanimoto Hiromu
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.64907

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mushroom body output differentiates memory processes and distinct memory-guided behaviors2021

    • Author(s)
      Ichinose Toshiharu、Kanno Mai、Wu Hongyang、Yamagata Nobuhiro、Sun Huan、Abe Ayako、Tanimoto Hiromu
    • Journal Title

      Current Biology

      Volume: 31 Issue: 6 Pages: 1294-1302

    • DOI

      10.1016/j.cub.2020.12.032

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Presynaptic nicotinic receptor in dopamine terminals mediates learned odor choice2024

    • Author(s)
      Yamagata N, Ichikawa R, Takahashi N, Abe A, Katayama N, Tanimoto H
    • Organizer
      Asia Pacific Drosophila Neurobiology Conference 3 (APDNC3)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nicotinic acetylcholine receptor in dopamine neurons regulates learned odor choice2023

    • Author(s)
      Yamagata N, Ichikawa R, Takahashi N, Abe A, Katayama N, Tanimoto H
    • Organizer
      日本比較生理生化学会 第45回大阪大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 学習依存的な匂い選択行動におけるドーパミン プレシナプスのニコチン受容体機能2023

    • Author(s)
      山方恒宏, 市川梨乃, 阿部綾子, 片山統裕, 谷本拓
    • Organizer
      日本動物学会 第94回 山形大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Presynaptic nicotinic receptor in dopamine neurons mediates learned odor choice2023

    • Author(s)
      Yamagata N, Ichikawa R, Takahashi N, Abe A, Katayama N, Tanimoto H
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Regulation of dopamine neurons for proper valuation2022

    • Author(s)
      Nobuhiro Yamagata, Hiromu Tanimoto
    • Organizer
      26th International Congress of Entomology, Helsinki, Finland
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ハエの“価値観”を支える神経機構2022

    • Author(s)
      山方 恒宏
    • Organizer
      阪大・京大・東北大 生命科学系3研究科合同セミナー
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Heterogeneity in dopamine reward system for evaluation2022

    • Author(s)
      Nobuhiro Yamagata
    • Organizer
      The University of Iowa, Department of Biology Seminar
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] ショウジョウバエ脳における受容体地図の構築と機能解析2021

    • Author(s)
      山方 恒宏
    • Organizer
      第2回トータルバイオミメティクス研究会 応用物理学会
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2020-02-06   Modified: 2025-01-30  

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