Molecular mechanisms for calcium-mediated refinement of competitive synaptic wiring in the brain

2009 Fiscal Year Self-evaluation Report

• Project/Area Number: 19100005
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Hokkaido University
• Principal Investigator: WATANABE Masahiko Hokkaido University, 大学院・医学研究科, 教授 (70210945)
• Project Period (FY): 2007 – 2011
• Keywords: シナプス / 脳 / 発達 / 小脳 / 大脳皮質

Research Abstract

生後早期の発達過程において、経験・訓練・学習に伴うシナプスの使用状況に応じてシナプス回路の強化と除去が起こる。その結果、未熟なシナプス回路は機能的で正確な投射関係を備えたシナプス回路へとリファインされ、認知・言語・技能・知能などの神経機能が飛躍的に発達する。現在、シナプスおけるグルタミン酸受容体(GluR)の活性化とそれによる細胞内Ca^<2+>濃度や伝達効率の変化が、この活動依存的なシナプス回路発達を促進することがわかってきている。本研究では、GluRおよびその下流で細胞機能制御に関わる分子群に着目し、競合的なシナプス回路の発達・維持の分子細胞機構を、神経解剖学・神経生理学・発生学・行動学の観点から解析することにより、その共通原理を解明する。

Research Products

• [Journal Article] Endocannabinoids and CB1 receptors mediate C-fiber-dependent heterosynaptic plasticity in spinalcord (2009)
  • Author(s): Pernia-Andrade AJ, Kato A, Witschi R, Nyilas R, Katona I, Freund TF, Watanabe M, Filitz J, Koppert W, Schiittler J, Guangchen J, Neugebauer V, Marcasino G, Lutz B, Vanegas H, Zeilhofer HU
  • Journal Title: Science 325 Pages: 760-764
• [Journal Article] NMDA receptor GluN2B (GluRe2/NR2B) subunit Is crucial for channel function, postsynaptic macromolecular organization, and actin cytoskeleton at hippocampal CA3 synapses (2009)
  • Author(s): Akashi K, Kakizaki T, Kamiya H, Fukaya M, Yamasaki M, Abe M, Natsume R, Watanabe M, Sakimura K
  • Journal Title: J. Neurosci 29 Pages: 10869-10882
• [Journal Article] Translocation of a "winner" climbing fiber to the Purkinje cell dendrite and subsequent elimination of "losers" from the soma in developing cerebellum (2009)
  • Author(s): Hashimoto K, Ichikawa R, Kitamura K, Watanabe M, Kano M
  • Journal Title: Neuron 63 Pages: 106-118
• [Journal Article] Spinocerebellar ataxia type 6 knock-in mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant Cav2.1 channels (2008)
  • Author(s): Watase K, Barrett CF, Miyazaki T, Ishiguro T, Ishikawa K, Hu Y, Unno T, Sun Y, Kasai S, Watanabe M, Gomez CM, Mizusawa H, Tsien RW, Zoghbi HY
  • Journal Title: Proc.Natl.Acad.Sci.USA 105 Pages: 11987-11992
• [Journal Article] Cbln1 Regulates Rapid Formation and Maintenance of Excitatory Synapses in Mature Cerebellar Purkinje Cells in vitro and in vivo (2008)
  • Author(s): Ito-Ishida A, Miura E, Emi K, Matsuda K, Iijima K, Narumi S, Kondo T, Kohda K, Watanabe M, Yuzaki M
  • Journal Title: J. Neurosci 28 Pages: 5920-5930
• [Journal Article] Dual coupling of T-type Ca^<2+> channels shapes sleep-related oscillations in thalamic dendrites (2008)
  • Author(s): Cueni L, Canepari M, Lujan R, Watanabe M, Bond CT, Adelman JP, Luthi A
  • Journal Title: Nature Neurosci 11 Pages: 683-692
• [Journal Article] Glutamate transporters regulate lesion-induced period plasticity in the developing somatosensory cortex (2008)
  • Author(s): Takasaki C, Okada R, Mitani A, Fukaya M, Yamasaki M, Fujihara Y, Shirakawa T, Tanaka K, Watanabe M
  • Journal Title: J. Neurosci 28 Pages: 4995-5006
• [Journal Article] Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP4 (2008)
  • Author(s): Matsuda S, Miura E, Matsuda K, Kakegawa W, Kohda K, Watanabe M, Yuzaki M
  • Journal Title: Neuron 57 Pages: 730-745
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRd2 (2008)
  • Author(s): Kakegawa W, Miyazaki T, Emi K, Matsuda K, Kohda K, Motohashi J, Mishina M, Kawahara S, Watanabe M, Yuzaki M
  • Journal Title: J Neurosci 28 Pages: 1460-0468
• [Journal Article] Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellum (2007)
  • Author(s): Nishiyama H, Fukaya M, Watanabe M, Linden D
  • Journal Title: Neuron 56 Pages: 472-487
• [Journal Article] Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus (2007)
  • Author(s): Uchigashima M, Fukaya M, Watanabe M, Kamiya H
  • Journal Title: J. Neurosci 27 Pages: 8088-8100
• [Journal Article] Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum (2007)
  • Author(s): Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M
  • Journal Title: J. Neurosci 27 Pages: 3663-3676
• [Journal Article] Cblnl is a ligand for an orphan glutamate receptor d2, a bidirectional synaptic organizer
  • Author(s): Matsuda K, Miura E, Miyazaki T, Kakegawa W, Emi K, Narumi S, Fukazawa Y, Itoh-Ishida A, Kondo T, Shigemoto R, Watanabe M, Yuzaki M
  • Journal Title: Science (in press)
• [Journal Article] Preferential localization of muscarinic M1 receptor on dendritic shaft and spine of cortical pyramidal cells and its anatomical evidence for volume transmission
  • Author(s): Yamasaki M, Matsui M, Watanabe M
  • Journal Title: J. Neurosci (in press)
• [Presentation] Coordinated molecular organization of 2-arachidonoyl glycerol-mediated endocannabinoid signaling triggered by mGluR activation (2008)
  • Author(s): Watanabe M
  • Organizer: 6th International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Sicily (Italy)
  • Year and Date: 20080914-20080919
• [Presentation] Glutamate transporters provide a 'winner-takes-more' strategy to activity-dependent synapse refinement (2008)
  • Author(s): Watanabe, M
  • Organizer: The 38th Seiriken/Soukendai International Conference (Stock and flow of functional molecules in synapses
  • Place of Presentation: Okazaki (Japan)
  • Year and Date: 20080317-20080319
• [Book] みる見るわかる脳・神経科学入門講座 (2008)
  • Author(s): 渡辺雅彦
  • Publisher: 羊土社(改訂版)