| 研究課題/領域番号 |
22KF0335
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| 補助金の研究課題番号 |
22F22386 (2022)
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 (2023)
補助金 (2022) |
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| 応募区分 | 外国 |
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| 審査区分 |
小区分46010:神経科学一般関連
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| 研究機関 | 慶應義塾大学 |
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研究代表者 |
柚崎 通介 慶應義塾大学, 医学部(信濃町), 教授 (40365226)
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| 研究分担者 |
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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| 研究期間 (年度) |
2023-03-08 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
2,300千円 (直接経費: 2,300千円)
2024年度: 700千円 (直接経費: 700千円)
2023年度: 1,100千円 (直接経費: 1,100千円)
2022年度: 500千円 (直接経費: 500千円)
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| キーワード | ドーパミン / シナプス / 側坐核 / 背側被蓋野 |
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| 研究開始時の研究の概要 |
In the present study, I will investigate how dopaminergic pathways are formed to achieve their neurotransmission, focusing on the VTA-NAc mesolimbic dopaminergic pathway. I will accomplish three specific goals. First, I will characterize synaptic and non-synaptic contact sites along dopaminergic axons. Second, I will identify molecules involved in these contact sites. Finally, I will elucidate how synaptic and non-synaptic contact sites regulate dopaminergic functions. I expect to accomplish these goals and address long-standing questions in the mesolimbic dopaminergic pathway.
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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