Elucidation of the mechanism of modulation of synaptic transmission by the regulation of intracellular calcium release

• Project/Area Number: 15K14309
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: The University of Tokyo
• Principal Investigator: Manabe Toshiya 東京大学, 医科学研究所, 教授 (70251212)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経科学 / 生理学 / 生体分子 / 脳・神経 / 遺伝子 / シナプス伝達 / 可塑性 / カルシウム

Outline of Final Research Achievements

In this study, we tried to elucidate roles of molecules that regulate calcium dynamics. We analyzed the functions of the molecules whose roles in calcium dynamics are not well known, using synapse site-specific gene-targeted mice. In the electrophysiological analysis with hippocampal slices, long-term potentiation of excitatory synaptic transmission was significantly reduced in postsynaptic site-specific Molecule A-deficient mice, whereas synaptic responses were increased during prolonged low-frequency stimulation in presynaptic terminal-specific Molecule A-deficient mice. We also found the possibility of the impairment in behavioral tests in Molecule B-deficient mice.

Research Products

• [Int'l Joint Research] University of California, San Diego/San Diego State University(米国)
• [Int'l Joint Research] University of California, San Diego/San Diego State University(米国)
• [Journal Article] NMDA receptor-independent LTP in hippocampal interneurons (2017)
  • Author(s): Manabe, T.
  • Journal Title: J. Physiol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking (2016)
  • Author(s): Nakamura et al.
  • Journal Title: Nat. Commun. Volume: 7 Issue: 1 Pages: 10861-10861
  • DOI: 10.1038/ncomms10861
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders (2016)
  • Author(s): Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
  • Journal Title: Nat Communications Volume: 7 Issue: 1 Pages: 10594-10594
  • DOI: 10.1038/ncomms10594
  • NAID: 120006535052
  • URL: https://pure.teikyo.jp/en/publications/6d10cbbf-3e7f-4e5b-bfce-ab50e6dde489
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The active zone protein CAST regulates synaptic vesicle recycling and quantal size in the mouse hippocampus. (2016)
  • Author(s): Kobayashi S, Hida Y, Ishizaki H, Inoue E, Tanaka-Okamoto M, Yamasaki M, Miyazaki T, Masahiro F, Kitajima I, Takai Y, Watanabe M, Ohtsuka T, Manabe T
  • Journal Title: Eur J Neurosci. Volume: 44 Issue: 5 Pages: 2272-2284
  • DOI: 10.1111/ejn.13331
  • Peer Reviewed / Open Access
• [Journal Article] IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging (2015)
  • Author(s): Wakabayashi et al.
  • Journal Title: Neurosci. Lett. Volume: 599 Pages: 20
  • DOI: 10.1016/j.neulet.2015.05.019
  • URL: https://pure.teikyo.jp/en/publications/e107f492-0f2a-4929-afdd-a90dcc40fc7e
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Generation and characterization of calsyntenin triple knockout mice (2017)
  • Author(s): Mori, K., Koebis, M., Ohno, H., Kobayashi, S., Manabe, T., Aiba, A. and Iino, Y.
  • Organizer: The Physiological Society of Japan, The 94th Annual Meeting
  • Place of Presentation: アクトシティー浜松（静岡県浜松市）
  • Year and Date: 2017-03-30
• [Presentation] Functional analyses of the CDKL5, a causative gene for severe neurodevelopmental disorders accompanied by intractable epilepsies (2015)
  • Author(s): Tanaka et al.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: McCormick Place in Chicago, USA
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] CDKL5 controls NMDA receptor function and regulates memory, emotion and seizure susceptibility (2015)
  • Author(s): Tanaka et al.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-09-13
• [Book] Annual Review神経２０１７ (2017)
  • Author(s): 真鍋 俊也
  • Total Pages: 281
  • Publisher: 中外医学社
• [Remarks] 東京大学 医科学研究所 基礎医科学部門 神経ネットワーク分野 ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/NeuronalNetwork/Neuronal_Network/Index_japanese.htm
• [Remarks] 東京大学 医科学研究所 基礎医科学部門 神経ネットワーク分野
  • URL: http://www.ims.u-tokyo.ac.jp/NeuronalNetwork/Neuronal_Network/Index_japanese.htm