| Project/Area Number |
15H04274
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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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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高雄 啓三 富山大学, 研究推進機構 研究推進総合支援センター, 教授 (80420397)
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| Co-Investigator(Renkei-kenkyūsha) |
AGETA NATSUMI (ISHIHARA NATSUMI) 名古屋大学, 大学院理学研究科, 講師 (60547561)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | シナプス / 細胞骨格 / 足場 / セプチン / 認知機能 / マウス / 電子顕微鏡 / 海馬歯状回 / 空間弁別障害 / ライブイメージング / グリア突起 / セプチン細胞骨格 / グリア / グルタミン酸代謝 / 足場蛋白質 / tripartiteシナプス / 遺伝子改変マウス / グルタミン酸受容体 / 小脳 / スパイン / グルタミン酸トランスポーター / 運動学習 |
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| Outline of Final Research Achievements |
The perforant path (pp)-granule cell (GC) synapse is poorly characterized at molecular/subcellular level. Here we show that mice that lack a pan-neuronal subunit of the septin cytoskeleton, pass hippocampus-dependent tasks. However, they consistently underperform in specific tasks that require discrimination among distinct spatial contexts. Hippocampal dentate gyrus (DG) neuron-selective supplementation of the septin subunit restores their performance, while the local depletion recapitulates the defects in wild-type mice. EM morphometry of three major hippocampal subregions shows normal synapse density, PSD area, and spine volume, but reveals a significant scarcity of spine apparatus that is most severe in the pp-GC synapse. Live imaging of septin-depleted primary cultured DG neurons reveals low frequency in ER entry from dendritic shafts into spines. These and other findings indicate a septin-mediated postsynaptic mechanism required in pp-GC synapses for spatial pattern separation.
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