競合的シナプス回路成熟の構造基盤と分子基盤

2007 Fiscal Year Annual Research Report

• Project/Area Number: 17023001
• Research Institution: Hokkaido University
• Principal Investigator: 渡辺 雅彦 Hokkaido University, 大学院・医学研究院, 教授 (70210945)
• Keywords: 小脳 / シナプス / グルタミン酸 / 発達 / 遺伝子改変動物

Research Abstract

今回、神経トレーサー法と免疫組織化学を組み合わせた形態解析技法を行い、mGluR1欠損マウスおよびPKCγ欠損マウスにおける登上線維支配様式について、以下の表現型を明らかにした。
1)近位樹状突起に対する登上線維の支配領域が縮小し、細胞体支配が残存した。
2)多重支配を引き起こす余剰な登上線維支配は主に細胞体に残存し、一部は樹状突起基部にも残存した。
3)余剰な登上線維は、近隣のプルキンエ細胞を支配する登上線維の比較的短い側枝として、分子層やプルキンエ細胞層内を横走してやってきた。
4)多重支配を招く近隣細胞間を横走する登上線維の投射様式は、生後14日令までは野生型と欠損マウスのどちらにも頻繁に観察された。
5)その後の発達過程において、多重支配を招く横走する登上線維は野生型マウスで急速に消失したのに対して、欠損マウスでは残存した。
以上の結果は、正常発達における登上線維による多重支配の終局段階が、優勢な単一登上線維が細胞体から近位樹状突起へとトランスロケートしながら支配領域を拡大する一方、劣勢な登上線維は細胞体〜樹状突起基部に留め置かれた状況になっていることを示唆する。ここにおいて、mGIuR1伝達系は平行線維シナプス活動を細胞内へと伝達することにより、優勢な登上線維支配をより強化促進する一方、余剰で劣勢な登上線維による支配を細胞体や樹状突起基部から除去することにより、単一支配へ移行させる分子機構であると結論した。

Research Products

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• [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum. (2007)
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• [Journal Article] Number and density of AMPA receptors in individual synapses in the cerebellum as revealed by SDS-digested freeze-fracture replica labeling. (2007)
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• [Journal Article] Phospholipase CB3 is distributed in both somatodendritic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in morse Purkinje cell subsets. (2007)
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• [Journal Article] Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats. (2007)
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  • Journal Title: Dev. Neurobiol. 67 Pages: 909-923
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• [Journal Article] Characterization of a transneuronal cytokine family Cbln. regulation of secretion by heteromeric assembly. (2007)
  • Author(s): Iijima, T., Miura, E., Matsuda, K., Kondo, T., Kamekawa, Y., Watanabe, M., Yuzaki, M.
  • Journal Title: Eur. J. Neurosci. 25 Pages: 1049-1057
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• [Journal Article] Ca^<2+> Permeability of the channel pore is not essential for the 2 glutam ate receptor to regulate synaptic plasticity and motor coordination. (2007)
  • Author(s): Kakegawa, W., Miyazaki, T., Hirai, H., Motohashi, J., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: J. Physiol. (London) 579 Pages: 729-735
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• [Journal Article] Segmental and complementary expression of L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase and neutral amino acid transporter ASCT1 in the mouse kidney. (2007)
  • Author(s): Takasaki, C., Miura, E., Watanabe, M.
  • Journal Title: Biomed. Res. 28 Pages: 61-69
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• [Journal Article] Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. (2007)
  • Author(s): Kakizawa, S., Kishimoto, Y., Hashimoto, K., Miyazaki, T., Furutani, K., Shimizu, H., Fukaya, M., Nishi, M., Sakagami, H., Ikeda, A., Kondo, H., Kano, M., Watanabe, M., Iino, M., Takeshima, H.
  • Journal Title: EMBO J. 26 Pages: 1924-1933
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• [Journal Article] Phospholipase C 4 expression reveals the continuity of cerebellar topography through development. (2007)
  • Author(s): Marzban, H., Chung, S., Watanabe, M., Hawkes, R.
  • Journal Title: J. Comp. Neurol. 502 Pages: 857-871
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• [Journal Article] Phosphorylation of extracellular signal-regulated kinase in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation. (2007)
  • Author(s): Polgar, E., Campbell, AD., MacIntyre, LM., Watanabe, M., Todd AJ
  • Journal Title: Mol. Pain 3 Pages: 4
  • Peer Reviewed
• [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: 363-3676
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• [Journal Article] Distribution of type 1 cannabinoid receptor(CB1)immunoreactive axons in the mouse hypothalamus. (2007)
  • Author(s): Wittmann, G., Deli, L., Kallo, I., Hraboviszky, E., Watanabe, M., Loposits, Z., Fekete, C.
  • Journal Title: J. Comp. Neurol. 503 Pages: 270-279
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• [Journal Article] Expression of the vesicular glutamate trasporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. (2007)
  • Author(s): Brumovsky, P., Watanabe, M., Hokfelt, T.
  • Journal Title: Neuroscience 147 Pages: 469-490
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• [Journal Article] CD3 and IgG Fc receptor regulate cerebellar functions. (2007)
  • Author(s): Nakamura, K., Hirai, H., Torashima, T., Miyazaki, T., Tsurui, H., Xiu, Y., Ohtsuji, M., Lin, Q.S., Tsukamoto, K., Nishimura, H., Ono, M., Watanabe, M., Hirose, S.
  • Journal Title: Mol. Cell Biol. 27 Pages: 5128-5134
  • Peer Reviewed
• [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
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• [Journal Article] Identification of the sites of 2-arachidonoylglycerol synthesis and actionimply retrograde endocannabinoid signaling at both GABAergic and glutamatergic synapses in the ventral tegmental area. (2007)
  • Author(s): Matyas, F., Urban, GM., Watanabe, M., Mackie, K., Aimmer, A., Freund, TF., Katona, I.
  • Journal Title: Neuropharmacology 54 Pages: 95-107
  • Peer Reviewed
• [Journal Article] Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and non-motoneuronal phenotypes. (2007)
  • Author(s): Niemann, S., Kanki, H., Fukui, Y., Takao, K., Fukaya, M., Hynynen, MN., Churchill, MJ., Shefner, JM., Bronson, RT., Watanabe, M., Brown, Jr, R., Miyakawa, T., Itohara, S., Hayashi, Y.
  • Journal Title: Eur.J.Neurosci. 26 Pages: 1407-1420
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• [Journal Article] Involvement of nitric ocide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells. (2007)
  • Author(s): Makara, JK., Katona, I., Nyiri, G., Nemeth, B., Watanabe, M., Vente, Jde., Freund, TF., Hajos, N.
  • Journal Title: J.Neurosci. 27 Pages: 10211-10222
  • Peer Reviewed
• [Journal Article] Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death. (2007)
  • Author(s): Nishiyama, J., Miura, E., Mizushima, N., Watanabe, M., Yuzak, M.
  • Journal Title: Autophagy 3 Pages: 591-596
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Altered features in mutant cerebellar Purkinje cells lacking junctophilins. (2007)
  • Author(s): Ikeda, A., Miyazaki, T., Kakizawa, S., Okuno, Y., Tsuchiya, S., Myomoto, A., Saito, S., Yamamoto, T., Yamazaki, T., Iino, M., Tsujimoto, G., Watanabe, M., Takeshima, H.
  • Journal Title: Biochem.Biophys.Res.Commun. 363 Pages: 835-839
  • Peer Reviewed
• [Journal Article] Regulation of long-term depression and climbing fiber territory by GluRe2 at parallel fiber synapses through its cariboxyl terminal domain in cerebellar Purkinje cells. (2007)
  • Author(s): Uemura, T., Kakizawa, T., Yamasaki, M., Sakimura, K., Watanabe, M., Iino, M., Mishina, M.
  • Journal Title: J Neurosci 27 Pages: 12096-12108
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• [Journal Article] Early postnatal stress affects the serotoergic function in the median raphe nuclei of adult rats. (2007)
  • Author(s): Konno, K., Matsumoto, M., Togashi, H., Yamaguchi, T., Izumi, T., Watanabe, M., Iwanaga, T., Yoshioka, M.
  • Journal Title: Brain Res. 1172 Pages: 60-66
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• [Journal Article] RGS2 modulates GABAB receptor-GIRK channel coupling in dopamine neurons of the ventral tegmental area. (2007)
  • Author(s): Labouebe, G., Lomazzi, M., Cruz, HG., Lujan, R., Li, M., Yanagawa, Y., Obata, K., Watanabe, M., Wickman, K., Slesinger, P., Luscher, C.
  • Journal Title: Nature Neurosci 10 Pages: 1559-1568
  • Peer Reviewed
• [Journal Article] Postsynaptic GABAB receptor signalling enhances LTD in mouse cerebellar Purkinje cells. (2007)
  • Author(s): Kamikubo, Y., Tabata, T., Kakizawa, S., Kawakami, D., Watanabe, M., Ogura, A., Iino, M., Kano, M
  • Journal Title: J Physiol. 585 Pages: 549-563
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRe2.
  • 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 (In press)
  • Peer Reviewed
• [Journal Article] IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts and localizes with PSD-95 at extitatory synapses.
  • Author(s): Sakagami, H., Sanda, M., Fukaya, M., Miyazaki, T., Sukegawa, J., Yanagisawa, T., Suzuki, T., Fukunaga, K., Watanabe, M., Kondo, K.
  • Journal Title: Neurosci Res (In press)
  • Peer Reviewed
• [Journal Article] Down-regulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus.
  • Author(s): Ludanyi, A., Erass, L., Czirjak, s., Vajda, J., Halasz, P., Watanabe, M., Palkovits, M., Magloczky, Z., Freund, TF., Katona, I.
  • Journal Title: J Neurosci (In press)
  • Peer Reviewed
• [Journal Article] Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals.
  • Author(s): Nyilas, R., Dudok, B., Urban, GM., Mackie, K., Watanabe, M., Cravatt, BF., Freund, TF., Katona, I.
  • Journal Title: J Neurosci (In press)
  • Peer Reviewed
• [Journal Article] SK2 channel plasticity contributes to LTP at Shaffer collateral-CA1 synapses.
  • Author(s): Lin, MT., Lujan, R., Watanabe, M., Adelman, JP., Maylie, J.
  • Journal Title: Nature Neurosci. (In press)
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation,Bergmann glia and climbing fiber territory on Purkinje cells.
  • Author(s): Watanabe, F., Miyazaki, T., Takeuchi, T., Fukaya, M., Nomura, T., Noguchi, S., Mori, H., Sakimura, K., Watanabe, M., Mishina, M.
  • Journal Title: Eur.J.Neurosci. (In press)
  • Peer Reviewed
• [Presentation] 登上線維プルキンエ細胞投射系による単一支配化への分子機構 (2008)
  • Author(s): 渡辺 雅彦
  • Organizer: 第113回日本解剖学会シンポジウム
  • Place of Presentation: 大分県・大分大学
  • Year and Date: 2008-03-29
• [Presentation] Selective localization of NR3A subunit at climbing fiber-interneuron synapses in the cerebellum. (2007)
  • Author(s): Masahiro, Fukaya., Masahiko, Watanabe.
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego, California.USA
  • Year and Date: 20071103-07
• [Presentation] 小脳における登上線維-介在ニューロン間シナプス選択的に発現するNMDA受容体NR3Aサブユニットの分子解剖学的解析 (2007)
  • Author(s): 深谷 昌弘、渡辺 雅彦
  • Organizer: 第53回東北・北海道連合支部学術集会
  • Place of Presentation: 札幌・北海道医療大学
  • Year and Date: 20070929-30
• [Presentation] バーグマングリアに発現するAMPA型グルタミン酸受容体の輸送様式 (2007)
  • Author(s): 深谷昌弘、渡辺雅彦>
  • Organizer: Neuro 2007 第30回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20070910-12
• [Presentation] GLAST分子欠損マウスにおけるバーグマングリアの形態分化異常および形態学的登上線維多重支配 (2007)
  • Author(s): 宮崎太輔, 田中光一, 渡辺雅彦
  • Organizer: Neuro 2007 第30回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20070910-12
• [Presentation] Mlムスカリン性アセチルコリン受容体は終脳の投射ニューロンに豊富に発現している (2007)
  • Author(s): 山崎美和子、飯塚尭、渡辺雅彦
  • Organizer: Neuro 2007 第30回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20070910-12
• [Presentation] マウス終脳の特定の介在神経におけるPKC&alphaおよびPKC&gammaの細胞発現パターンの解析 (2007)
  • Author(s): 三浦会里子, 窪田圭志, 渡辺雅彦
  • Organizer: Neuro 2007 第30回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20070910-12
• [Presentation] 線条体における2-アラキドノイルグリセロールを介した逆行性シグナル伝達に関与する分子の細胞内配置 (2007)
  • Author(s): 内ヶ島基政, 鳴島円, 深谷昌弘, Istvan Katona, 狩野方伸, 渡辺雅彦
  • Organizer: Neuro 2007 第30回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 20070910-12
• [Presentation] Subcellular arrangement of molecules 2-arachidonlyl-glycerol-mediated retrograde signaling in the striatum. (2007)
  • Author(s): Motokazu, Uchigashima., Madoka, Narushima., Masahiro, Fukaya., Istvan, Katona., Masanobu, Kano., Masahiko, Watanabe.
  • Organizer: IBRO World Congress of Neuroscience
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 20070712-17
• [Presentation] マウス線条体における内因性カンナビノイド2-アラキドノイルグリセロールを介した逆行性伝達抑制の分子機構 (2007)
  • Author(s): 内ヶ島基政, 渡辺雅彦
  • Organizer: 日本顕微鏡学会北海道支部会
  • Place of Presentation: 札幌・コンペンションセンター
  • Year and Date: 2007-12-01
• [Presentation] 神経系における内在性カンナビノイドの分子解剖学 (2007)
  • Author(s): 渡辺 雅彦
  • Organizer: 日本麻酔科学会北海道東北支部第55回北海道麻酔科学会
  • Place of Presentation: 札幌・北海道大学
  • Year and Date: 2007-09-08
• [Presentation] 神経系における内在性カンナビノイドの合成・分解とその生理作用 (2007)
  • Author(s): 渡辺 雅彦
  • Organizer: 第28回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 札幌・札幌医大
  • Year and Date: 2007-09-01