| Project/Area Number |
20K06593
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
DESCHUTTER ERIK 沖縄科学技術大学院大学, 計算脳科学ユニット, 教授 (00466319)
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| Co-Investigator(Kenkyū-buntansha) |
HEPBURN Iain 沖縄科学技術大学院大学, 計算脳科学ユニット, 客員研究員 (20604200)
GALLIMORE Andrew 沖縄科学技術大学院大学, 計算脳科学ユニット, 客員研究員 (50838422)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Synapse / Plasticity / Hippocampus / Computational biology / Systems biology |
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| Outline of Research at the Start |
The probability of neurotransmitter release in response to an action potential is a fundamental variable regulating information transmission in the brain, although it remains poorly understood. We have developed a unique modeling technology that will allow us to build a detailed and realistic computational model of the complete synaptic vesicle cycle, which will allow us to explore how release probability is regulated at central nervous system synapses. We hope that this research could eventually have applications in the treatment of neurological disorders, such as Alzheimer’s disease.
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| Outline of Final Research Achievements |
We developed new technology for simulating vesicles in cells and related processes such as exocytosis, clustering, active transport and endocytosis. Such phenomena play crucial roles in biology, for example by controlling neurotransmitter release in nerve terminals, which is the fundamental process behind information transfer in the brain. Being able to simulate these systems computationally allows us to explore them in ways not previously possible, and uncover new insights into their function.
We used this new technology to develop a model of the synaptic vesicle cycle at a hippocampal en passant synapse to unprecedented spatial and molecular detail. In doing so, we uncovered many new insights into this system, such as the use of the distinct vesicle pools at different stimulation frequencies and the role of crucial molecules such as tomosyn-1 and Rab3-GTP in regulating neurotransmitter release. The tools developed will allow further discoveries to be made in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
神経情報伝達物質の放出は脳の情報伝達の根幹にあり、これらの異変はアルツハイマー病、パーキンソン病、そして統合失調症に関連すると考えられている。よって、神経伝達の理解を深める本研究の成果はこれらの病理学に大きく貢献し、治療法確立の礎となる。本研究で開発されたシミュレータは今後細胞内小胞のシミュレーションにも役立つ。
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