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Comprehensive expression profiling of dopamine receptors in a brain structure: a neuroanatomical logic towards understanding functional pleiotropy of dopamine

Research Project

Project/Area Number 17H04765
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Basic / Social brain science
Research InstitutionTohoku University

Principal Investigator

Yamagata Nobuhiro  東北大学, 生命科学研究科, 准教授 (50716248)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Keywordsドーパミン受容体 / ショウジョウバエ / キノコ体 / 学習 / 記憶 / ドーパミン / 受容体 / 学習・記憶
Outline of Final Research Achievements

Dopamine plays pivotal roles in diverse cognitive functions ranging from reward and motivation to feeding and sexual behaviors. Differential modulatory effects of dopamine neurotransmission may be defined by distinct expression profiles of functionally different receptor subtypes. We thus conducted systematic expression profiling of four dopamine receptors in the memory center of fruit flies, the mushroom body. By utilizing CRISPR/CAS9 genome editing techniques, we characterized the endogenous receptor gene and protein expressions. We found cellular and subcellular expressions distinct among receptor subtypes, which may characterize their functions as well as the functionality of the mushroom body's subcompartments. Our findings may provide neuroanatomical logic for dopamine neurotransmission causing opposing effects across different subdomains of a brain structure, which supports adaptive behaviors in an animal.

Academic Significance and Societal Importance of the Research Achievements

1つの神経伝達物質に対し、機能の異なる複数の受容体種が存在することは、神経伝達物質全般に当てはまり、神経伝達の基本原理のひとつであるが、その機能的意義はよく分かっていない。本研究成果は、ドーパミン応答の多様性を生む分子基盤として、異なる受容体種から成る受容体発現パターンがあることを示すもので、上記の機能的意義に直結する。また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」の十分な理解が不可欠であり、本成果はその理解につながる分子神経基盤を提供する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (7 results)

All 2020 2019 2018 Other

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

  • [Int'l Joint Research] Ludwig-Maximilians-Universitaet Muenchen(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Neurochemical Organization of the Drosophila Brain Visualized by Endogenously Tagged Neurotransmitter Receptors2020

    • Author(s)
      Kondo S, Takahashi T, Yamagata N, Imanishi Y, Katow H, Hiramatsu S, Lynn K, Abe A, Kumaraswamy A, Tanimoto H
    • Journal Title

      Cell Reports

      Volume: 30 Issue: 1 Pages: 284-297

    • DOI

      10.1016/j.celrep.2019.12.018

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Courtship behavior induced by appetitive olfactory memory.2019

    • Author(s)
      Onodera Y, Ichikawa R, Terao K, Tanimoto H, Yamagata N.
    • Journal Title

      J Neurogenet.

      Volume: 2019 Apr 8 Issue: 2 Pages: 1-9

    • DOI

      10.1080/01677063.2019.1593978

    • Related Report
      2019 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neural Correlates of Odor Learning in the Presynaptic Microglomerular Circuitry in the Honeybee Mushroom Body Calyx2018

    • Author(s)
      Joachim Haenicke, Nobuhiro Yamagata, Hanna Zwaka, Martin Nawrot, Randolf Menzel
    • Journal Title

      eNeuro

      Volume: 5(3) Issue: 3 Pages: ENEURO.0128-18.2018

    • DOI

      10.1523/eneuro.0128-18.2018

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Neurochemical substrates underlying optimistic cognitive bias2019

    • Author(s)
      Nobuhiro Yamagata
    • Organizer
      2019 Asia-Pacific Drosophila Neuroscience Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dopamine receptor system in the associative center of the fly2019

    • Author(s)
      Nobuhiro Yamagata
    • Organizer
      5th NSI International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 脳の設計図の理解に先鞭 ~脳における神経伝達物質受容体のマッピング~

    • URL

      https://www.tohoku.ac.jp/japanese/2020/02/press20200213-05-brain.html

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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