Comprehensive expression profiling of dopamine receptors in a brain structure: a neuroanatomical logic towards understanding functional pleiotropy of dopamine
| Project/Area Number |
17H04765
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Basic / Social brain science
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(7 results)
