2023 Fiscal Year Final Research Report
Activity-dependent postsynaptic remodeling underlying memory consolidation
| Project/Area Number |
21H02579
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | シナプス / スパイン / 長期増強 / 記憶 / ミオシン / セプチン / 滑面小胞体 / リン酸化 |
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| Outline of Final Research Achievements |
Physiological significance of SEPT7T426 phosphorylation on the database was unknown, but our FRAP data showing a requirement of C-terminal 12 residues of SEPT7 in membrane localization, a higher mobility of SEPT7T426D than SEPT7, and similarity with MYH10 in terms of membrane localization and mobility, support our model in which the neural activity-dependent T426 phosphorylation releases SEPT7 from the membrane skeleton. 3D electron microscopy analysis of electrically stimulated mouse brains (an in vivo model of long-term memory) showed an increase in SEPT3 and MYO5A on ER membranes near dendritic spines in the hippocampus. The increase in ER-containing spines by electrical stimulation was not observed in the Sept3-null mice unlike their wild-type littermates. These data supports the working model.
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| Free Research Field |
分子神経生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、学習・記憶の基盤となるシナプス近傍の膜骨格のリモデリング機構の一端を明らかにした。過活動したシナプス近傍の小胞体膜上にSEPT3とMYO5Aが集積することは、「強いシナプス活動がSEPT3のリン酸化による遊離とMYO5Aの活性化を誘発し、両者がシナプス近傍のER膜上で会合してスパイン内へER を牽引する」という独自の作業仮説を支持する。本研究の結果に基づき、長期記憶のシナプス基盤と想定されるスパイン内ER伸展の分子メカニズムの解明と、他の長期記憶障害モデルにおいてもスパイン内ER伸展障害がみられるかの検証を進めている。
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