競合的シナプス回路成熟の構造基盤と分子基盤

2009 年度 研究成果報告書

• 研究課題/領域番号: 17023001
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 北海道大学
• 研究代表者: 渡辺 雅彦 北海道大学, 大学院・医学研究科, 教授 (70210945)
• 研究期間 (年度): 2005 – 2009
• キーワード: 小脳 / シナプス / グルタミン酸 / 発達 / 遺伝子改変動物

研究概要

ニューロンには莫大な数の同種および異種線維が入力し、それぞれが競合して機能的な神経回路が確立する。本研究では運動を制御する小脳の神経回路発達に焦点を当てその細胞分子メカニズムの解明に取り組んだ。その結果、小脳プルキンエ細胞に発現するGluD2と顆粒細胞から放出されるCbln1が共同して平行線維シナプスの形成・維持を促進する一方、登上線維支配を制限することにより単一支配の確立と維持に関わることを実証した。

研究成果

• [雑誌論文] Endocannabinoids and CB1 receptors mediate C-fiber-dependent heterosynaptic plasticity in spinalcord. (2009)
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• [雑誌論文] NMDA receptor GluN2B (GluRe2/NR2B) subunit Is crucial for channel function, postsynaptic macromolecular organization, and actin cytoskeleton at hippocampal CA3 synapses. (2009)
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• [雑誌論文] Evidence against AMPA receptor-lacking glutamatergic synapses in the superficial dorsal horn of the rat spinal cord. (2009)
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  • 査読あり
• [雑誌論文] Rescue of abnormal phenotypes in d2 glutamate receptor-deficient mice by the extracellular N-terminal and intracellular C-terminal domains of the d2 glutamate receptor. (2009)
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  • 査読あり
• [雑誌論文] Functional coupling between mGluR1 and Cav3. 1 T-type calcium channels underlies parallel fiber-induced fast calcium signaling within Purkinje cell dendritic spines. (2009)
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• [雑誌論文] Translocation of a "winner" climbing fiber to the Purkinje cell dendrite and subsequent elimination of "losers" from the soma in developing cerebellum. (2009)
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• [雑誌論文] The N-terminal domain of GluRδ2 recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo. (2009)
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  • 査読あり
• [雑誌論文] Cbln1 binds to specific postsynaptic sites at parallel fiber-Purkinje cell synapses in the cerebellum. (2009)
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  • 査読あり
• [雑誌論文] PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex. (2009)
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  • 査読あり
• [雑誌論文] Cbln1 accumulates and colocalizes with Cbln3 and GluRd2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum. (2009)
  • 著者名/発表者名: Miura E, Matsuda K, Morgan JI, Yuzaki M, Watanabe M
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  • 査読あり
• [雑誌論文] Left-right asymmetry of the hippocampal synapses with different subunit allocation of glutamate receptors. (2008)
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• [雑誌論文] Phospholipase Cb3 in mouse and human dorsal root ganglia and spinal cord is a possible target for treatment of neuropathic pain. (2008)
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  • 雑誌名: Proc. Natl. Acad. Sci. USA 105 ページ: 20004-20008
  • 査読あり
• [雑誌論文] Predominant expression of phospholipase Cb1 in telencephalic principal neurons and cerebellar interneurons, and its close allocation with related signaling molecules in somatodendritic neuronal elements. (2008)
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• [雑誌論文] Use-dependent amplification of presynaptic Ca2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse. (2008)
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  • 査読あり
• [雑誌論文] Spinocerebellar ataxia type 6 knock-in mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant Cav2. 1 channels. (2008)
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  • 査読あり
• [雑誌論文] Enhanced cerebellar LTD induction and OKR adaptation in mice lacking delphilin. (2008)
  • 著者名/発表者名: Takeuchi, T., Ohtsuki, G., Yoshida, T., Fukaya, M., Wainai, T., Yamashita M, Yamazaki Y, Mori, M., Sakimura, K., Kawamoto, S., Watanabe, M., Hirano, T., Mishina, M.
  • 雑誌名: PLoS One 3(5)(on-line journal) ページ: e2297
  • 査読あり
• [雑誌論文] Cbln1 Regulates Rapid Formation and Maintenance of Excitatory Synapses in Mature Cerebellar Purkinje Cells in vitro and in vivo. (2008)
  • 著者名/発表者名: Ito-Ishida A, Miura E, Emi K, Matsuda K, Iijima K, Narumi S, Kondo T, Kohda K, Watanabe M, Yuzaki M
  • 雑誌名: J. Neurosci 28 ページ: 5920-5930
  • 査読あり
• [雑誌論文] Synapse formation and clustering of neuroligin-2 in the absence of GABAA receptors. (2008)
  • 著者名/発表者名: Patrizi A, Scelfo B, Viltono L, Briatore F, Fukaya M, Watanabe M, Strata P, Varoqueaux F, Brose N, Fritschy JM, Sassoe-Pognetto M
  • 雑誌名: Proc. Natl. Acad. Sci. USA 105 ページ: 13151-13156
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• [雑誌論文] Dual coupling of T-type Ca2+ channels shapes sleep-related oscillations in thalamic dendrites. (2008)
  • 著者名/発表者名: Cueni L, Canepari M, Lujan R, Watanabe M, Bond CT, Adelman JP, Luthi A
  • 雑誌名: Nature Neurosci 11 ページ: 683-692
  • 査読あり
• [雑誌論文] Glutamate transporters regulate lesion-induced period plasticity in the developing somatosensory cortex. (2008)
  • 著者名/発表者名: Takasaki C, Okada R, Mitani A, Fukaya M, Yamasaki M, Fujihara Y, ShirakawaT, Tanaka K, Watanabe M
  • 雑誌名: J. Neurosci 28 ページ: 4995-5006
  • 査読あり
• [雑誌論文] Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP4. (2008)
  • 著者名/発表者名: Matsuda S, Miura E, Matsuda K, Kakegawa W, Kohda K, Watanabe M, Yuzaki M
  • 雑誌名: Neuron 57 ページ: 730-745
  • 査読あり
• [雑誌論文] SK2 channel plasticity contributes to LTP at Shaffer collateral-CA1 synapses. (2008)
  • 著者名/発表者名: Lin MT, Lujan R, Watanabe M, Adelman JP, Maylie J
  • 雑誌名: Nature Neurosci. 11 ページ: 170-177
  • 査読あり
• [雑誌論文] Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals. (2008)
  • 著者名/発表者名: Nyilas R, Dudok B, Urban GM, Mackie K, Watanabe M, Cravatt BF, Freund TF, Katona I
  • 雑誌名: J Neurosci 28 ページ: 1058-1063
  • 査読あり
• [雑誌論文] Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. (2008)
  • 著者名/発表者名: Ludanyi A, Erass L, Czirjak S, Vajda J, Halasz P, Watanabe M, Palkovits M, Magloczky Z, Freund TF, Katona I
  • 雑誌名: J Neurosci 28 ページ: 2976-2990
  • 査読あり
• [雑誌論文] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRd2 (2008)
  • 著者名/発表者名: Kakegawa W, Miyazaki T, Emi K, Matsuda K, Kohda K, Motohashi J, Mishina M, Kawahara S, Watanabe M, Yuzaki M
  • 雑誌名: J Neurosci 28 ページ: 1460-0468
  • 査読あり
• [雑誌論文] RGS2 modulates GABAB receptor-GIRK channel coupling in dopamine neurons of the ventral tegmental area. (2007)
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  • 雑誌名: Nature Neurosci 10 ページ: 1559-1568
  • 査読あり
• [雑誌論文] Regulation of long-term depression and climbing fiber territory by GluRd2 at parallel fiber synapses through its cariboxyl terminal domain in cerebellar Purkinje cells. (2007)
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  • 雑誌名: J Neurosci 27 ページ: 12096-12108
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• [雑誌論文] Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellum. (2007)
  • 著者名/発表者名: Nishiyama H, Fukaya M, Watanabe M, Linden D
  • 雑誌名: Neuron 56 ページ: 472-487
  • 査読あり
• [雑誌論文] Involvement of nitric ocide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells. (2007)
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  • 雑誌名: J. Neurosci 27 ページ: 10211-10222
  • 査読あり
• [雑誌論文] Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus. (2007)
  • 著者名/発表者名: Uchigashima M, Fukaya M, Watanabe M, Kamiya H
  • 雑誌名: J. Neurosci 27 ページ: 8088-8100
  • 査読あり
• [雑誌論文] Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. (2007)
  • 著者名/発表者名: Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M
  • 雑誌名: J. Neurosci. 27 ページ: 3663-3676
  • 査読あり
• [雑誌論文] Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. (2007)
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  • 雑誌名: EMBO J. 26 ページ: 1924-1933
  • 査読あり
• [雑誌論文] Ca2+ permeability of the channel pore is not essential for the d2 glutamate receptor to regulate synaptic plasticity and motor coordination. (2007)
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  • 査読あり
• [雑誌論文] Characterization of a transneuronal cytokine family Cbln. regulation of secretion by heteromeric assembly. (2007)
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  • 査読あり
• [雑誌論文] Phospholipase Cb is distributed in both somatodendritic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in mouse Purkinje cell subsets. (2007)
  • 著者名/発表者名: Nomura S, Fukaya M, Tsujioka T, Wu D, Watanabe M
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  • 査読あり
• [雑誌論文] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum. (2007)
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  • 査読あり
• [雑誌論文] Indispensability of glutamate transporter GLAST and GLT1 to brain development. (2006)
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  • 査読あり
• [雑誌論文] Abundant distribution of TARP g-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites. (2006)
  • 著者名/発表者名: Fukaya M, Tsujita M, Yamazaki M, Kushiya E, Abe M, Akashi K, Natsume R, Kano M, Kamiya H, Watanabe M, Sakimura K
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  • 査読あり
• [雑誌論文] Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins. (2006)
  • 著者名/発表者名: Moriguchi S, Nishi M, Komazaki S, Sakagami H, Miyazaki T, Masumiya H, Saito S, Watanabe M, Kondo H, Yawo H, Fukunaga K, Takeshima H
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  • 査読あり
• [雑誌論文] Distinct expression of Cbln family mRNAs in developing and adult mouse brains. (2006)
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  • 査読あり
• [雑誌論文] NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity. (2006)
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  • 査読あり
• [雑誌論文] Localization of diacylglycerol lipase-a round postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. (2006)
  • 著者名/発表者名: Yoshida T, Fukaya M, Uchigashima M, Kamiya H, Kano M, Watanabe M
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  • 査読あり
• [雑誌論文] Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain. (2006)
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  • 査読あり
• [雑誌論文] CB1 is the major cannabinoid receptor at excitatory presynaptic site in the hippocampus and cerebellum. (2006)
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  • 査読あり
• [雑誌論文] Impaired cerebellar functions in mutant mice lacking DNER. (2006)
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  • 査読あり
• [雑誌論文] Complementary stripes of phospholipase Cs3 and Cs4 expression by Purkinje cell subsets in the mouse cerebellum. (2006)
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  • 査読あり
• [雑誌論文] Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. (2005)
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  • 査読あり
• [雑誌論文] Clbn1 is essential for synaptic integrity and information processing in the cerebellum. (2005)
  • 著者名/発表者名: Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, Parris J, Rong Y, Watanabe M, Yuzaki M, Morgan JI
  • 雑誌名: Nature Neurosci. 8 ページ: 1534-1541
  • 査読あり
• [雑誌論文] Complementary roles of cholecystokinin and parvalbumin expressing GABAergic neurons in hippocampal network oscillations. (2005)
  • 著者名/発表者名: Klausberger T, Marton LF, O'Neill J, Huck JHJ, Dalezios Y, Fuentealba P, Suen W-Y, Papp E, Kaneko T, Watanabe M, Csicsvari J, Somogyi P
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  • 査読あり
• [雑誌論文] Spatial diversity in gene expression for VDCCg subunit family in developing and adult mouse brains. (2005)
  • 著者名/発表者名: Fukaya M, Yamazaki M, Sakimura K, Watanabe M
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  • 査読あり
• [雑誌論文] Target-cell-specific left-right asymmetry of NMDA receptor content in Schaffer collateral synapses in e1 knock-out mice. (2005)
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  • 査読あり
• [雑誌論文] Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. (2005)
  • 著者名/発表者名: Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CVE, Kawaguchi Y, Nakao K, Nabeshima Y
  • 雑誌名: Neuron 47 ページ: 201-213
  • 査読あり
• [雑誌論文] Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. (2005)
  • 著者名/発表者名: Takayasu Y, Iino M, Kakegawa W, Maeno H, Watase K, Wada K, Miyazaki T, Watanabe M, Tanaka K, Ozawa
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  • 査読あり
• [雑誌論文] Control of synaptic connection by glutamate receptor d2 n the mature cerebellum. (2005)
  • 著者名/発表者名: Takeuchi T, Miyazaki T, Watanabe M, Mori H, Sakimura K, Mishina M
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  • 査読あり
• [雑誌論文] NR2-to-NR3B subunit conversion of NMDA receptor in early postnatal motoneurons. (2005)
  • 著者名/発表者名: Fukaya M, Hayashi Y, Watanabe M
  • 雑誌名: Eur. J. Neurosci. 21 ページ: 1432-1436
  • 査読あり
• [雑誌論文] Rescue of abnbormal phenotypes of the d glutamate receptor-null mice by mutant d transgenes. (2005)
  • 著者名/発表者名: Hirai H, Miyazaki T, Kakegawa W, Matsuda S, Mishina M, Watanabe M, Yuzaki M
  • 雑誌名: EMBO Rep 6 ページ: 90-95
  • 査読あり
• [雑誌論文] Preferential localization of muscarinic M1 receptor on dendritic shaft and spine of cortical pyramidal cells and its anatomical evidence for volume transmission.
  • 著者名/発表者名: Yamasaki M, Matsui M, Watanabe M
  • 雑誌名: J. Neurosci (in press)
  • 査読あり
• [雑誌論文] Cbln1 is a ligand for an orphan glutamate receptor d2, a bidirectional synaptic organizer.
  • 著者名/発表者名: 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
  • 雑誌名: Science (in press)
  • 査読あり
• [学会発表] Coordinated molecular organization of 2-arachidonoyl glycerol-mediated endocannabinoid signaling triggered by mGluR activation. (2008)
  • 著者名/発表者名: Watanabe M
  • 学会等名: 6th International Meeting on Metabotropic Glutamate Receptors
  • 発表場所: Sicily (Italy)
  • 年月日: 20080914-20080919
• [学会発表] Glutamate transporters provide a 'winner-takes-more' strategy to activity-dependent synapse refinement. (2008)
  • 著者名/発表者名: Watanabe, M
  • 学会等名: The 38th Seiriken/Soukendai International Conference (Stock and flow of functional molecules in synapses.
  • 発表場所: Okazaki (Japan)
  • 年月日: 20080317-20080319
• [図書] みる見るわかる脳・神経科学入門講座改訂版 (2008)
  • 著者名/発表者名: 渡辺雅彦
  • 出版者: 羊土社
• [図書] 脳神経外科学大系1。神経科学, (山浦晶総編集) (2006)
  • 著者名/発表者名: 渡辺雅彦
  • 総ページ数: 50-67
  • 出版者: 中山書店
• [図書] 組織細胞化学2005, (日本組織細胞化学会編) (2005)
  • 著者名/発表者名: 渡辺雅彦
  • 総ページ数: 23-36
  • 出版者: 学際企画
• [備考]
  • URL: http://www.med.hokudai.ac.jp/~anat-2w/