競合的シナプス回路成熟の構造基盤と分子基盤

2008 Fiscal Year Annual Research Report

• Project/Area Number: 17023001
• Research Institution: Hokkaido University
• Principal Investigator: 渡辺 雅彦 Hokkaido University, 大学院・医学研究科, 教授 (70210945)
• Keywords: 小脳 / シナプス / グルタミン酸トランスポーター / 発達 / 遺伝子改変動物 / 登上線維 / mGluR1 / プルキンエ細胞

Research Abstract

平成20年度は、次の2つの研究項目を実施した。
・グルタミン酸受容体mGluR1シグナル伝達系によるプルキンエ細胞シナプス回路発達制御
活動依存的な細胞内カルシウム放出を誘導するmGluR1伝達系のプルキンエ細胞シナプス回路発達における機能的役割を、mGluR1欠損マウスおよびPKCg欠損マウスを用いて、解剖学的および電気生理学的手法を用いて平行線維支配と登上線維支配の競合関係、登上線維支配様式の変化を検討した。その結果、生後第2週までの余剰な登上線維による細胞体支配は野性型および欠損マウスの両者に認められたが、それ以後野性型では一本の優勢な登上線維のみが樹状突起に伸展し他の劣勢な線維は除去されたが、欠損マウスでは劣勢な登上線維も細胞体から樹状突起へと伸展して多重支配が残存することが判明した。これと平行して、欠損マウスでは優勢な登上線維の伝達物質放出機能の増強が悪いことも判明した。
・グルタミン酸トランスポーターによるプルキンエ細胞シナプス回路発達制御
バーグマングリアに豊富なグルタミン酸トランスポーターGLAST欠損成体マウスに発生する登上線維の多重支配の形態学的異常を、発生過程における刈込み障害によるものか、正常な刈込み後に生じるものかを、神経解剖学的および電気生理学的に検討した。その結果、シナプス形成期である生後第3週を過ぎてから、欠損マウスにおいてグリアによるシナプス被いに障害が現れ、これと平行して登上線維による多重支配が増悪していくことが判明した。

Research Products

• [Journal Article] Type 1 cannabinoid receptor (CB1)-containing axons innervate the hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons (2009)
  • Author(s): Deli L, Wittmann G, Kallo I, Lechan RM, Watanabe M, Liposits Z, Fekete C
  • Journal Title: Endocrinology (in press)
  • Peer Reviewed
• [Journal Article] The endocannabinoid system is modulated in response to spinal cord injury in rats (2009)
  • Author(s): Garcia-Ovejero D, Arevalo-Martin A, Petrosino S, Docagne F, Hagen C, Bisogno T, Watanabe M, Guaza C, Di Marzo M, Molina-Holgado E
  • Journal Title: Neurobiol. Disease (in press)
  • Peer Reviewed
• [Journal Article] CB1 cannabinoid receptor-dependent and -independent inhibition of depolarization-induced calcium influx in oligodendrocytes. (2009)
  • Author(s): Mato S, Alberdi E, Ledent C, Watanabe M, Matute C
  • Journal Title: Glia (in press)
  • Peer Reviewed
• [Journal Article] The postsynaptic density protein, IQ-ArfGEF/BRAG1, can interact with IRSp53 through its proline-rich sequence (2009)
  • Author(s): Sanda M, Kamata A, Katsumata O, Fukunaga K, Watanabe M, Kondo K, Sakaaami H
  • Journal Title: Brain Res (in press)
  • Peer Reviewed
• [Journal Article] Impaired neurogenesis in embryonic spinal cord of Phgdh knockout mice, aserine deficiency disorder model (2009)
  • Author(s): Kawakami Y, Yoshida K, Hoon Yang J, Azuma N, Tanaka H, Sakai K, Hashikawa T, Watanabe M, Kuhara S, Hirabayashi Y, Furuya S
  • Journal Title: Neurosci. Res (in press)
  • Peer Reviewed
• [Journal Article] Neurokinin 1 receptor-expressing projection neurons in laminae III and IV of the rat spinal cord have synaptic AMPA receptors that contain GluR2, GluR3 and GluR4 subunits (2009)
  • Author(s): Todd AJ, Polgar E, Yasaka T, Bailey MES, Watt C, Watanabe M
  • Journal Title: Eur J Neurosci (in press)
  • Peer Reviewed
• [Journal Article] PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex (2009)
  • Author(s): Zhang J, Xu T, Hallett PJ, Watanabe M, Grant SGN, Isacson O, Yao W-D
  • Journal Title: J. Neurosci (in press)
  • Peer Reviewed
• [Journal Article] Cbln1 binds to specific postsynaptic sites at parallel fiber-Purkinje cell synaoses in the cerebellum (2009)
  • Author(s): Matsuda K, Kondo T, Iijima T, Matsuda S, Watanabe M, Yuzaki M
  • Journal Title: Eur J Neurosci (in press)
  • Peer Reviewed
• [Journal Article] Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons (2009)
  • Author(s): Fukushima, F., Nakao, K., Shinoe, T., Fukaya, M., Muramatsu S, Sakimura, K., Kataoka, H., Mori, H., Watanabe, M., Manabe, T., Mishina, M
  • Journal Title: ProS ONE 4 Pages: e3993
  • Peer Reviewed
• [Journal Article] The N-terminal domain of GluRδ2 recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo (2009)
  • Author(s): Kakegawa W, Miyazaki T, Kohda K, Matsuda K, Emi K, Motohashi J, Watanabe M, Yuzaki M
  • Journal Title: J. Neurosci (in press)
  • Peer Reviewed
• [Journal Article] Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. (2008)
  • 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 28 Pages: 2976-2990
  • Peer Reviewed
• [Journal Article] Multiple substrates for synaptic cannabinoid signaling in dopaminergic and non-dopaminergic neurons of the ventral tegmental area (2008)
  • Author(s): Matvas F, Urban GM. Watanabe M, Mackie K, Aimmer A, Freund TF Katona I
  • Journal Title: Neuropharmacology 54 Pages: 95-107
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRδ2 (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: 1460-1468
  • Peer Reviewed
• [Journal Article] IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts and localizes with PSD-95 at excitatory synapses (2008)
  • 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 60 Pages: 199-212
  • Peer Reviewed
• [Journal Article] Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals (2008)
  • Author(s): Nyilas R, Dudok B, Urban GM, Mackie K, Watanabe M, Cravatt BF, Freund TF, Katona I
  • Journal Title: J Neurosci 28 Pages: 1058-1063
  • Peer Reviewed
• [Journal Article] SK2 channel plasticity contributes to LTP at Shaffer collateral-CA1 synapses (2008)
  • Author(s): Lin MT, Luian R, Watanabe M, Adelman JP, Maylie J
  • Journal Title: Nature Neurosci 11 Pages: 170-177
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia and climbing fiber territory on Purkinje cells (2008)
  • Author(s): Watanabe F, Miyazaki T, Takeuchi T, Fukaya M, Nomura T, Noguchi S, Mori H, Sakimura K, Watanabe M, Mishina M(Correspondinq author)
  • Journal Title: Eur. J. Neurosci 27 Pages: 836-854
  • Peer Reviewed
• [Journal Article] Expression of AMPA receptor subunits at synapses in laminae I-III of the rodent spinal dorsal horn (2008)
  • Author(s): Polgar E. Watanabe M, Hartmann B,Grant SGN, Todd TA
  • Journal Title: Mol Pain(on-line journal) 4 Pages: 5
  • Peer Reviewed
• [Journal Article] Cerebellar pathology in transgenic mice expressing the pseudorabies virus immediate-early protein IE180 (2008)
  • Author(s): Tomioka Y, Miyazaki M,Taharaguchi S, Yoshino S, Morimatsu M. Uede T, Ono E, Watanabe M(Corresponding author)
  • Journal Title: Eur. J. Neurosci 27 Pages: 2115-2132
  • Peer Reviewed
• [Journal Article] Role of the internal Shank-binding segment of glutamate receptor δ2 in synaptic localization and cerebellar functions (2008)
  • Author(s): Yasumura M, Uemura T, Yamasaki M,Sakimura K, Watanabe M, Mishina M
  • Journal Title: Neurosci Lett 433 Pages: 146-151
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adultmouse CNS. (2008)
  • Author(s): Miwa H, Fukaya M, Watabe AM, Watanabe M. Manabe T
  • Journal Title: J. Physiol 586(10) Pages: 2539-2550
  • Peer Reviewed
• [Journal Article] Cell type-specific subunit composition of G-protein-gated potassium channels in the cerebellum (2008)
  • Author(s): Aguado C, Colon J, Ciruela F,Schlaudraff F, Cabariero MJ, Perry C, Watanabe M, Liss B, Wickman K,Lujan R
  • Journal Title: J Neurochem 105 Pages: 497-511
  • Peer Reviewed
• [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.(Corresponding author)
  • Journal Title: J. Neurosci 28 Pages: 4995-5006
  • Peer Reviewed
• [Journal Article] Dual coupling of T-type Ca2+ 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
  • Peer Reviewed
• [Journal Article] Synapse formation and clustering of neuroligin-2 in the absence of GABAA receptors (2008)
  • Author(s): Patrizi A, Scelfo B, Viltono L, Briatore F, Fukaya M, Watanabe M, Strata P, Varoqueaux F, Brose N, Fritschy JM, Sassoe-Pognetto M
  • Journal Title: Proc. Natl. Acad. Sci. USA 105(35) Pages: 13151-13156
  • Peer Reviewed
• [Journal Article] Cloning and characterization of E-dlg, a novel splice variant of mouse homologue of the Drosophila discs large tumor suppressor binds preferentially to SAP102 (2008)
  • Author(s): Mao P, Tao Y-X, Fukaya M, Li D, Tao T, Watanabe M, Johns RA
  • Journal Title: IUBMB (International Union of Biochemistry and Molecular Biology) Life 60 Pages: 684-692
  • Peer Reviewed
• [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, lijima K, Narumi S, Kondo T, Kohda K, Watanabe M, Yuzaki M
  • Journal Title: J. Neurosci 28 Pages: 5920-5930
  • Peer Reviewed
• [Journal Article] N-Ethylmaleimide-sensitive fusion protein (NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after infla mmation (2008)
  • Author(s): Katano T, Furue H, Okuda-Ashitaka E, Tagaya M, Watanabe M, Yoshimura M, Ito S
  • Journal Title: Eur. J. Neurosci 27 Pages: 3161-3170
  • Peer Reviewed
• [Journal Article] Enhanced cerebellar LTD induction and OKR adaptation in mice lacking delphilin (2008)
  • Author(s): 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.
  • Journal Title: PLoS One(on-line journal) 3(5) Pages: e2297
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Use-dependent amplification of presynaptic Ca^<2+> signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse. (2008)
  • Author(s): Shimizu H, Fukaya M, Yamasaki M, Watanabe M, Manabe T, Kamiya H
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 11998-12003
  • Peer Reviewed
• [Journal Article] Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats (2008)
  • Author(s): Nogueiras R, Veyrat-Durebex C, Suchanek PM, Klein M, Tschop J, Caldwell C, Woods SC, Wittmann G, Watanabe M, Liposits Z, Fekete C, Reizes O, Rohner-Jeanrenaud F, Tschop MH
  • Journal Title: Diabetes 57 Pages: 2977-2991
  • Peer Reviewed
• [Journal Article] Expression and possible role of creatine transporter in the brain and at the blood-cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant (2008)
  • Author(s): Tachikawa M, Fujinawa J, Takahashi M, Kasai Y, Fukaya M, Sakai K, Yamazaki M, Tomi M, Watanabe M, Sakimura K, Terasaki T, Hosoya K
  • Journal Title: J. Neurochem 107 Pages: 768-778
  • Peer Reviewed
• [Journal Article] Loss of Hrs in the central nervous system causes accumulation of ubiquitinated proteins and neurodegeneration (2008)
  • Author(s): Tamai K, Tanaka N, Toyoshima M, Yamamoto N, Owada Y, Kiyonari H, Ueno Y, Ono M, Shimosegawa T, Watanabe M, Sugamura K
  • Journal Title: Am. J. Pathol 173 Pages: 1806-1817
  • Peer Reviewed
• [Journal Article] Predominant expression of phospholipase Cβ1 in telencephalic principal neurons and cerebellar interneurons, and its close allocation with related signaling molecules in somatodendritic neuronal elements (2008)
  • Author(s): Fukaya M, Uchigashima M, Nomura S, Hasegawa Y, Kikuchi H, Watanabe M(Corresponding author)
  • Journal Title: Eur J Neurosci 28 Pages: 1744-1759
  • Peer Reviewed
• [Journal Article] Phospholipase Cβ3 in mouse and human dorsal root ganglia and spinal cord is a possible target for treatment of neuropathic pain (2008)
  • Author(s): Shi TJ, Liu SX, Hammarberg H, Watanabe M, Xu ZQ, Hokfelt T
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 20004-20008
  • Peer Reviewed
• [Journal Article] Left-right asymmetry of the hippocampal synapses with different subunit allocation of glutamate receptors (2008)
  • Author(s): Shinohara Y, Hirase H, Watanabe M, Itakura M, Takahashi M, Shiqemoto R
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 19498-19503
  • Peer Reviewed
• [Journal Article] Large projection neurons in lamina l of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors (2008)
  • Author(s): Polgar E, Al-Khater K, Shehab S, Watanabe M. Todd AJ
  • Journal Title: J. Neurosci 28 Pages: 13150-13160
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase β accumulates on the perisynaptic site of medium spiny neurons in the striatum (2008)
  • Author(s): Hozumi Y, Fukaya M, Adachi N, Saito N, Otani K, Kondo H, Watanabe M, Goto K
  • Journal Title: Eur J Neurosci 28 Pages: 2409-2422
  • Peer Reviewed
• [Journal Article] Cbln1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum (2008)
  • Author(s): Miura E, Matsuda K, Morgan JI, Yuzaki M, Watanabe M (Corresponding author)
  • Journal Title: Eur J Neurosci 29 Pages: 693-706
  • Peer Reviewed
• [Presentation] マウス小脳および海馬におけるセクレトグラニンII(SgII)の局在様式 (2009)
  • Author(s): 宮崎太輔・渡辺雅彦
  • Organizer: 第114回解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-30
• [Presentation] M1受容体を介するコリン作動性神経の伝達様式とシナプス伝達調節機構 (2009)
  • Author(s): 山崎美和子, 渡辺雅彦
  • Organizer: 第114回解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-30
• [Presentation] マウス歯状回における2-アラキドノイルグリセロールを介した逆行性伝達抑制機構に関与する分子の免疫組織化学的分布 (2009)
  • Author(s): 内ヶ島基政・渡辺雅彦
  • Organizer: 第114回解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-30
• [Presentation] マウス小脳ピンスーにおける化学的シナプス伝達機構の検討 (2009)
  • Author(s): 岩倉淳, 渡辺雅彦
  • Organizer: 第114回解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-30
• [Presentation] 成体マウス大脳皮質におけるニューロン周囲オリゴデンドロサイトの化学的特性の検討 (2009)
  • Author(s): 高崎千尋・内ヶ島基政・渡辺雅彦
  • Organizer: 第114回解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-30
• [Presentation] GLASTはバーグマングリアの形態分化および登上線維単一支配の維持に必要である (2008)
  • Author(s): 宮崎太輔, 渡辺雅彦
  • Organizer: 日本解剖学会第54回東北・北海道連合支部学術集会
  • Place of Presentation: 市民プラザ・ビッグアイ(郡山市)
  • Year and Date: 20080906-07
• [Presentation] M1アセチルコリン受容体はマウスの大脳皮質・海馬の投射ニューロンに豊富に発現している (2008)
  • Author(s): 山崎美和子, 渡辺雅彦
  • Organizer: 日本解剖学会第54回東北・北海道連合支部学術集会
  • Place of Presentation: 市民プラザ・ビッグアイ(郡山市)
  • Year and Date: 20080906-07
• [Presentation] Preferential localization of muscarinic M1 receptor in spines and thin dendrites of cortical principal neurons and its anatomical evidence for volume transmission (2008)
  • Author(s): Yamasaki M, Watanabe M.
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: The Ceneva Palexpo Conference Center, Geneva, Switzerland
  • Year and Date: 20080712-16
• [Presentation] Distinct cellular and subcellular expression of calcineurins in the mouse cerebellum (2008)
  • Author(s): Miura E, Watanabe M.
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: The Ceneva Palexpo Conference Center, Geneva, Switzerland
  • Year and Date: 20080712-16
• [Presentation] Monoacylglycerol lipase is expressed not only in presynaptic terminals, butalso in astrocytes in the mouse forebrain (2008)
  • Author(s): Uchigashima M, Watanabe M.
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: The Ceneva Palexpo Conference Center, Geneva, Switzerland
  • Year and Date: 20080712-16
• [Presentation] Glutamate transporters magnify critical period plasticity in developing somatosensory cortex (2008)
  • Author(s): Takasaki C, Okada R, Mitani A, Fukaya M, Hujihara Y, Shirakawa T, Kouichi Tanaka K, Watanabe M.
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: The Ceneva Palexpo Conference Center, Geneva, Switzerland
  • Year and Date: 20080712-16
• [Presentation] マウス小脳におけるプルキンエ細胞のPKCγバンド状発現 (2008)
  • Author(s): 江本美穂, 渡辺雅彦
  • Organizer: Neuro 2008第31回日本神経科学大会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 20080709-11
• [Presentation] GLAST is essential for the maintenance of climbing fiber monoinnervation through preventing local ectopic innervations to neighbouring and remote Purkinje cells and promoting cytological differentiation of Bergmann glia (2008)
  • Author(s): Miyazaki T, Yamasaki M, Kouichi Tanaka K, Watanabe M.
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: The Ceneva Palexpo Conference Center, Geneva, Switzerland
  • Year and Date: 20080702-16
• [Presentation] マウス小脳ピンスーにおける化学的シナプス伝達機構の形態学的検討 (2008)
  • Author(s): 岩倉淳, 渡辺雅彦
  • Organizer: 2008年日本顕微鏡学会北海道支部会
  • Place of Presentation: 北海道大学
  • Year and Date: 2008-12-01