2023 Fiscal Year Research-status Report
The molecular basis of dopaminergic transmission: Identifying and Characterizing Cellular Adhesion Sites
| Project/Area Number |
22KF0335
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| Allocation Type | Multi-year Fund |
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| Research Institution | Keio University |
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Principal Investigator |
柚崎 通介 慶應義塾大学, 医学部(信濃町), 教授 (40365226)
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| Co-Investigator(Kenkyū-buntansha) |
DILINA TUERDE 慶應義塾大学, 医学部(信濃町), 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2025-03-31
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| Keywords | ドーパミン / シナプス / 側坐核 / 背側被蓋野 |
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| Outline of Annual Research Achievements |
In this study, I investigated how dopaminergic pathways are formed to achieve their neurotransmission focusing on the mesolimbic VTA-NAc pathway. To achieve this, I outlined three specific aims: Firstly, I aim to visualize and characterize cell-cell contact sites along the mesolimbic pathway using the GRAPHIC method. Secondly, I intend to identify the cell adhesion molecules involved in these contact sites. Finally, I aim to elucidate how these cell adhesion molecules regulate dopaminergic functions.
Through these aims, my goal is to gain deeper insights into the intricate mechanisms underlying dopaminergic pathway formation and functions.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In 2023, I successfully visualized cell-cell contact sites along the mesolimbic pathway using the GRAPHIC method, employing both immunofluorescence and electron microscopy techniques. Through these approaches, I identified the cell adhesion molecules involved in the mesolimbic VTA-NAc pathway. These molecules were found at the contact sites between dopamine fibers and medium spiny neurons. Notably, their absence resulted in a reduced number of dopamine varicosities and VMAT2 expression.
Additionally, I identified the receptors for these cell adhesion molecules on the medium spiny neurons. Knockout of the receptors revealed a similar dysfunction of dopamine fibers and a reduction in such cell adhesions. These findings provide significant insights into the role of these molecules in regulating dopamine transmission in the VTA-NAc pathway.
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| Strategy for Future Research Activity |
To deepen our comprehension of the functional significance of these cell adhesion molecules within the VTA-NAc pathway, I intend to conduct conditional knockout experiments targeting these molecules to evaluate their impact on dopamine transmission and reward behaviors.
Consequently, this study is expected to offer a comprehensive understanding of the molecular mechanisms governing the regulation of the dopaminergic system. Additionally, I intend to summarize the findings and submit them for publication in 2024.
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| Causes of Carryover |
昨年度は計画が順調に進み、計画していた一部の実験を遂行する必要性が無くなった。そのため、それらの実験を遂行すべく予算を次年度に繰越し、新たに得た実験結果に基づく実験計画に注力し、本実験に必要な試薬等の消耗品の費用を拡充する予定
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Research Products
(1 results)
