Morphological analysis for the maintenance of climbing fiber-Purkinje cell mono-innervation in the cerebellum

• Project/Area Number: 18700335
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hokkaido University
• Principal Investigator: MIYAZAKI Taisuke Hokkaido University, 大学院医学研究科, 助教 (90374230)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 小脳 / プルキンエ細胞 / 登上線維 / 平行線維 / グルタミン酸受容体 / 神経標識法 / 遺伝子改変動物 / 臨界期

Research Abstract

小脳プルキンエ細胞 (PC)は、数十万本の平行線維 (PF)と1本の登上線維 (CF)による興奮性入力を受けている。幼若期のPCは複数のCFによる多重支配を受けているが、発達過程において余剰なCFは排除され、生後3週目までには一つのPCがただ1本のCFによって支配される単一支配が確立する。この単一支配化には、PFシナプス後部特異的に発現するグルタミン酸受容体GluRd2が重要であることが知られている。本研究では、誘導型GluRd2欠損マウスを用いて、CF-PC単一支配化の維持にGluRd2が関与しているかどうかを明らかにすべく行われた。誘導型GluRd2欠損マウスのCF-PC支配様式を、神経標識法および免疫組織化学法を用いて解析したところ、(1)分子欠損誘導後8週からCF多重支配が認められ、GluRd2欠損領域でCF支配領域の拡大が認められた、(2)分子欠損誘導後8週からtransverse branchと呼ばれるCF側枝が側方のPCに対して異所性支配を行い、CF-PC多重支配を引き起こしている様子が観察されたという2つの所見が得られた。以上の結果はGluRd2がCF側枝による側方支配を抑制することで成体期におけるCF-PC単一支配の維持に関わっていることを強く示唆するものであった。

Research Products

• [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] Spinocerebellar ataxia type 6 knockin 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 U S A 105(33) Pages: 11987-92
  • Peer Reviewed
• [Journal Article] Cerebellar pathology in transgenic mice expressing the pseudorabies virus immediate-early protein IE 180 (2008)
  • Author(s): Tomioka Y, Miyazaki T, Taharaguchi S, Yoshino S, Morimatsu M, Uede T, Ono E, Watanabe M
  • Journal Title: Eur J Neurosci 27(8) Pages: 2115-2132
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning 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
  • Journal Title: Eur J Neurosci 27(4) Pages: 836-54
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRdelta2 (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(6) Pages: 1460-8
  • NAID: 120006399304
  • Peer Reviewed
• [Journal Article] IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses (2008)
  • Author(s): Sakagami H, Sanda M, Fukaya M, Miyazaki T, Sukegawa J, Yanagisawa T, Suzuki T, Fukunaga K, Watanabe M, Kondo H
  • Journal Title: Neurosci Res 60(2) Pages: 199-212
  • NAID: 10031136221
  • Peer Reviewed
• [Journal Article] Spinocerebellar ataxia type 6 knockin 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, Ishikaw a K, Hu Y, Unno T, Sun Y, Kasai S, Watanabe M, Gomez CM, Mizusawa H, Tsien RW, Zoghbi HY.
  • Journal Title: Proc Nati Acad Sci USA 105 Pages: 11987-11992
  • Peer Reviewed
• [Journal Article] IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. (2008)
  • Author(s): Sakagami H, Sanda M, Fukaya M, Miyazaki T, Sukegawa J, Yanagisawa T, Suzuki T, Fukunaga K, Watanabe M, Kondo H.
  • Journal Title: Neurosci Res 60 Pages: 199-212
  • NAID: 10031136221
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRdelta2. (2008)
  • Author(s): Kakegawa W, Miyazaki T, EmiK, Matsuda K, Kohda K, Motohashi J, Mishina M, Kawahara S, Watanabe M, Yuzaki M.
  • Journal Title: J Neurosci. 28 Pages: 1460-1468
  • NAID: 120006399304
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning 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.
  • Journal Title: Eur J Neurosci 27 Pages: 836-854
  • Peer Reviewed
• [Journal Article] Cerebellar pathology in transgenic mice expressing the pseudorabies virusimmediate-early protein IE 180. (2008)
  • Author(s): Tomioka Y, Miyazaki T, Taharaguchi S, Yoshino S, Morimatsu M, Uede T, Ono E, Watanabe M.
  • Journal Title: Eur J Neurosci (In press)
  • Peer Reviewed
• [Journal Article] Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins (2007)
  • Author(s): Ikeda A, Miyazaki T, Kakizawa S, Okuno Y, Tsuchiya S, Myomoto A, Saito SY, Yamamoto T, Yamazaki T, Iino M, Tsujimoto G, Watanabe M, Takeshima H
  • Journal Title: Biochem Biophys Res Commun 363(3) Pages: 835-9
  • Peer Reviewed
• [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(7) Pages: 1924-33
  • Peer Reviewed
• [Journal Article] Ca2+ permeability of the channel pore is not essential for the delta2 glutamate 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: 729-35
  • Peer Reviewed
• [Journal Article] Ca2+ permeability of the channel pore is not essential for the delta2 glutamate 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 579 Pages: 729-735
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins. (2007)
  • Author(s): Ikeda A, Miyazaki T, Kakizawa S, Okuno Y, Tsuchiya S, Myomoto A, Saito SY, 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] M. Ca2+ permerability of the channel pore is not essential for the delta2 glutamate 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 579 Pages: 729-735
• [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
• [Journal Article] Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family (2006)
  • Author(s): Miyazaki T, Hashimoto K, Uda A, Sakagami H, Nakamura Y, Saito SY, Nishi M, Kume H, Tohgo A, Kaneko I, Kondo H, Fukunaga K, Kano M, Watanabe M, Takeshima H
  • Journal Title: FEBS Lett 580(17) Pages: 4057-64
  • Peer Reviewed
• [Journal Article] Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins (2006)
  • Author(s): Moriguchi S, Nishi M, Komazaki S, Sakagami H, Miyazaki T, Masumiya H, Saito SY, Watanabe M, Kondo H, Yawo H, Fukunaga K, Takeshima H
  • Journal Title: Proc Natl Acad Sci U S A 103(28) Pages: 10811-6
  • Peer Reviewed
• [Journal Article] Impaired cerebellar functions in mutant mice lacking DNER (2006)
  • Author(s): Tohgo A, Eiraku M, Miyazaki T, Miura E, Kawaguchi SY, Nishi M, Watanabe M, Hirano T, Kengaku M, Takeshima H
  • Journal Title: Mol Cell Neurosci 31(2) Pages: 326-33
  • Peer Reviewed
• [Journal Article] Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins (2006)
  • Author(s): Moriguchi, S., Nishi, M., Komazaki, S., Sakagami, H., Miyazaki, T., Masumiya, H., Saito, S.Y., Watanabe, M., Kondo, H., Yawo, H., Fukunaga, K., Takeshima, H
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 10811-10816
• [Journal Article] Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family (2006)
  • Author(s): Miyazaki, T., Hashimoto, K., Uda, A., Sakagami, H., Nakamura Y., Saito, S.Y., Nishi, M., Kume, H., Tohgo, A., Kaneko, I., Kondo, H., Fukunaga, K., Kano, M., Watanabe, M., Takeshima, H
  • Journal Title: FEBS Lett. 580 Pages: 4057-4064
• [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(岡山)
• [Presentation] マウス小脳および海馬におけるセクレトグラニンII(Sgll)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(岡山)
• [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: 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(福島・郡山)
• [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): Taisuke Miyazaki, Miwako Yamasaki, Kouichi Tanaka, Masahiko Watanabe
  • Organizer: 6th FENS Forum of Europian Neuroscience
  • Place of Presentation: Palexpo Conference Center (Geneva, Switzerland)
• [Presentation] グルタミン酸受容体GluR2は成体マウスにおける登上線維単一支配の維持に必須である (2008)
  • Author(s): 宮崎 太輔・渡辺 雅彦
  • Organizer: 第113回解剖学会総会・全国学術集会
  • Place of Presentation: 大分医科大学(大分)
• [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): Taisuke Miyazaki, Miwako Yamasa ki, Kouichi Tanaka, Masahiko Wat anabe
  • Organizer: 6^<th> FENS Forum of Europian Neuroscience
  • Place of Presentation: Palexpo Conference Center (Geneva, Switzerland)
• [Presentation] グルタミン酸受容体GluRδ2は成体マウスにおける登上線維単一支配の維持に必須である (2008)
  • Author(s): 宮崎 太輔・渡辺 雅彦
  • Organizer: 第113回解剖学会総会・全国学術集会
  • Place of Presentation: 大分県・大分大学
• [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 (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: パシフィコ横浜(横浜)
• [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局所的な異所性プルキンエ細胞支配による登上線維多重支配 (2007)
  • Author(s): 宮崎 太輔・渡辺 雅彦
  • Organizer: 2007年 第112回解剖学会総会・全国学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
• [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
• [Presentation] GLAST is essential for cytological differentiation of Bergmann glia and climbing fiber monoinnervation by suppressing local ectopic innervation (2006)
  • Author(s): 宮崎 太輔・田中 光一
  • Organizer: 第29回日本神経科学大会
  • Place of Presentation: 国立京都国際会議場(京都)