| 研究課題/領域番号 |
22K06833
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分48020:生理学関連
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| 研究機関 | 京都府立医科大学 |
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研究代表者 |
SHERWOOD MARK 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60578160)
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| 研究期間 (年度) |
2022-04-01 – 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 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2024年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
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| キーワード | Channel-synapse / Synaptic-transmission / In-vivo recording / ATP-sensor / Intrinsic-NADH / synapse / purinergic / calcium / stim-metab coupling / CALHM channel |
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| 研究開始時の研究の概要 |
Communication between cells is key to nervous system function. Communication occurs at points of contact called synapses. Synapse are made of a presynaptic cell, a gap, and a post-synaptic cell. To communication the post-synaptic cell must release a chemical called a transmitter which crosses the gap between cells and stimulates the post-synaptic cell. If cells are communicating a lot then more transmitter will be needed. The aim of the current project is to understand how cells are able to control transmitter production and maintain effective communication between cells.
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| 研究実績の概要 |
Chemical synapses mediate rapid communication between excitable cells and are crucial to the function of the central and peripheral nervous systems. A novel chemical synapse, the ‘non-vesicular’ channel synapse employs conductive release of ATP (neurotransmitter) via large pore CALHM1/3 channels. To maintain synapse function, channel synapses must have stimulus-metabolic coupling to precisely match ATP production with demand. The current study is determining the molecular mechanism of stimulus-metabolic coupling at the channel-synapse. To this end we established in vivo functional imaging in taste cells.
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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 this fiscal year we have continued to establish techniques for the functional imaging of taste cell function in vivo required for objective 3, i.e. in vivo two-photon imaging of intrinsic NADH fluorescence in taste cells.
In the previous fiscal year we generated mice expressing ATP-sensor on the surface of taste cells. This sensor is required to detect synaptically released ATP, as detailed in objective 4. This sensor has a high sensitivity for ADP and ATP. We therefore generated new high sensitivity biosensors that are specific for ATP.
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| 今後の研究の推進方策 |
It is necessary to image synaptic release of ATP, however, at the time of in vivo imaging, it is impossible to know where the synapses are located within the tastebud. To solve this problem we perform four-dimensional imaging (XYZT) to capture the entire taste bud over time. The four-dimensional data generated is ill-suited to traditional region-of-interest based analysis. In the upcoming year (year-3) we will develop analysis tools for efficient ROI independent segmentation of synaptic ATP release from four-dimensional (XYZT) functional images of in vivo taste-buds.
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