Postsynaptic calcineurin regulates input-specific synapse formation
Project/Area Number |
17K08485
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General anatomy (including histology/embryology)
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Research Institution | Hokkaido University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | プルキンエ細胞 / カルシニューリン / GABA / シナプス特異性 / 抑制性シナプス / GABA受容体 / バスケット細胞 / カルシウム |
Outline of Final Research Achievements |
Cerebellar Purkinje cells form axo-spinous and axo-dendritic synapse with excitatory and inhibitory terminals, respectively. It has been unclear what mechanism regulates the input-specific synapse formation. To understand mechanism of the input-specific synapse formation, the present analysis focused on calcium-dependent phosphatase calcineurin, which regulates long-term synaptic transmission. By anatomical investigation, CNB1, a catalytic subunit of calcineurin expressed at Purkinje cells and molecular layer interneuron which send inhibitory input to Purkinje cells. Moreover, in Purkinje cell specific CNB1-deficient model mice, inhibitory terminals frequently contacted to excitatory Purkinje cell spines whose potsynapse expressed both excitatory and inhibitory neurotransmitter receptors. This result indicates that postsynaptic CNB1 regulates input-specific synapse formation in the developing cerebellum.
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Academic Significance and Societal Importance of the Research Achievements |
中枢神経系の多くは興奮性および抑制性ニューロンに大別され、それらの入力を受けるシナプス後部ではそれぞれの神経伝達物質に対応したシナプス形成様式と神経伝達物質受容体発現が見られる。このようなシナプス形成様式は神経終末依存的な分子機構があると考えられてきたが、その実態については不明な点が多く残されていた。本研究の結果から、長期シナプス伝達に関わることが知られているカルシニューリンがシナプス後部において入力特異的なシナプス形成様式に関わっていることが示唆された。この研究により得られた成果はこれまでのシナプス形成様式モデルとは一線を画し、今後の発展が期待される学術的意義の高いものであると考えられる
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Elavl3 is essential for the maintenance of Purkinje neuron axons2018
Author(s)
Ogawa Yuki、Kakumoto Kyoko、Yoshida Tetsu、Kuwako Ken-ichiro、Miyazaki Taisuke、Yamaguchi Junji、Konno Ayumu、Hata Junichi、Uchiyama Yasuo、Hirai Hirokazu、Watanabe Masahiko、Darnell Robert B.、Okano Hideyuki、Okano Hirotaka James
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 2722-2722
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum.2017
Author(s)
Choo M, Miyazaki T, Yamazaki M, Kawamura M, Nakazawa T, Zhang J, Tanimura A, Uesaka N, Watanabe M, Sakimura K, Kano M.
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Journal Title
Nat Commun.
Volume: 8(1)
Issue: 1
Pages: 195-195
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.2017
Author(s)
Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, Tamada K, Mizuma H, Onoe H, Watanabe Y, Monai H, Hirase H, Nakatani J, Inagaki H, Kawada T, Miyazaki T, Watanabe M, Sato Y, Okabe S, Kitamura K, Kano M, Hashimoto K, Suzuki H, Takumi T.
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Journal Title
Sci Adv.
Volume: 3(6)
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing a neurological disease in mice.2017
Author(s)
Aikawa T, Watanabe T, Miyazaki T, Mikuni T, Wakamori M, Sakurai M, Aizawa H, Ishizu N, Watanabe M, Kano M, Mizusawa H, Watase K.
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Journal Title
Hum Mol Genet.
Volume: 26(16)
Pages: 3094-3104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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