グリア-ニューロン相互認識に関わる機能分子と活動依存性分子動態

• Project/Area Number: 15082210
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institute for Physiological Sciences (2004-2007); Okazaki National Research Institutes (2003)
• Principal Investigator: 重本 隆一 National Institute for Physiological Sciences, 大脳皮質機能研究系, 教授 (20221294)
• Co-Investigator(Kenkyū-buntansha): 深澤 有吾 生理学研究所, 大脳皮質機能研究系, 助教 (60343745) ; 時田 美和子 (馬杉 美和子) 京都府立医科大学, 医学(系)研究科(研究院), 助手 (10420712)
• Project Period (FY): 2003 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥51,900,000 (Direct Cost: ¥51,900,000); Fiscal Year 2007: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2006: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2005: ¥10,600,000 (Direct Cost: ¥10,600,000); Fiscal Year 2004: ¥10,800,000 (Direct Cost: ¥10,800,000); Fiscal Year 2003: ¥10,500,000 (Direct Cost: ¥10,500,000)
• Keywords: グリア / ニューロン / GLT1 / GLAST / NG-2 / AMPA / グルタミン酸受容体 / レプリカ免疫電顕 / CAST / 凍結割断レプリカ / GABA受容体 / Ihチャネル / HCN2 / oligodendrocyte

Research Abstract

海馬の歯状回のアストログリア細胞上に存在する膜内粒子の集合とグルタミン酸トランスポーターGLAST,GLT1について、テタヌス刺激を与えて長期増強現象を起こした標本での凍結割断レプリカ免疫法による解析を進めた結果、膜内粒子がより大きな斑状の集合体を形成し、シナプス近傍にもGLT1の標識の優位な密度増加が認められた。これは、神経活動の増大に伴って、過剰なグルタミン酸を処理するために、グルタミン酸トランスポーターの発現が増加し、グルタミン酸放出部位に集まってくる可能性を示していると考えたが、刺激24時間後でも同様の変化が残っており、シナプスのみならずグリア細胞にも長期的な可塑性が存在する可能性を示した。
一方、小脳運動学習の発現におけるAMPA型受容体核サブユニットの役割を調べるために、バーグマングリア細胞に特異的にG1uR1がノックアウトされているマウスを解析したところ、全く正常のコントロールマウスと差がなく、トータルノックアウトマウスで認められた運動学習の障害の原因はバーグマングリア細胞に発現するG1uR1ではないことが明らかになった。

Research Products

• [Journal Article] GABA_B receptors are expressed in developing oligodendrocytes (2007)
  • Author(s): Luyt K
  • Journal Title: J Neurochem 100 Pages: 822-40
  • Peer Reviewed
• [Journal Article] Expression of group II metabotropic glutamate receptors in rat gustatory papillae (2007)
  • Author(s): Toyono T
  • Journal Title: Cell Tissue Res 328 Pages: 57-63
  • Peer Reviewed
• [Journal Article] HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels (2007)
  • Author(s): Whitaker GM
  • Journal Title: J Biol Chem 282 Pages: 22900-9
  • Peer Reviewed
• [Journal Article] Developing oligodendrocytes express functional GABA (B) receptors that stimulate cell proliferation and migration. (2007)
  • Author(s): Luyt K
  • Journal Title: J Neurochem 100 Pages: 822-840
• [Journal Article] Localization of metabotropic GABA receptor subunits GABA_<B1> and GABA_<B2> relative to synaptic sites in the rat developing cerebellum. (2006)
  • Author(s): Lujan R
  • Journal Title: Eur J Neurosci 23 Pages: 1479-1490
• [Journal Article] Localization of metabotropic GABA receptor subunits GABA_<B1> and GABA_<B2> relative to synaptic sites in the rat developing cerebellum. (2006)
  • Author(s): Lujan R
  • Journal Title: Eur.J Neurosci (in press)
• [Journal Article] Compartment-dependent co-localization of Kir3.2-containing K^+ channels and GABA_B receptors in CA1 pyramidal cells. (2006)
  • Author(s): Kulik A
  • Journal Title: J Neurosci (in press)
• [Journal Article] Differential distribution of release-related proteins in the hippocampal CA3 area as revealed by freeze-fracture replica labeling. (2005)
  • Author(s): Hagiwara A.
  • Journal Title: J Comp Neurol 489 Pages: 195-216
• [Journal Article] Neurogliaform neurons form a novel inhibitory network in the hippocampal CA1 area. (2005)
  • Author(s): Price CJ
  • Journal Title: J Neurosci 25 Pages: 6775-6786
• [Journal Article] Target-cell-specific left-right asymmetry of NMDA receptor content in schaffer collateral synapses in epsilon 1/NR2A knock-out mice. (2005)
  • Author(s): Wu Y
  • Journal Title: J Neurosci 25 Pages: 9213-9226
• [Journal Article] Number and density of AMPA receptors in single synapses in immature cerebellum. (2005)
  • Author(s): Tanaka J
  • Journal Title: J Neurosci 25 Pages: 799-807
• [Journal Article] Differential distribution of release-related proteins in the hippocampal CA3 area as revealed by freeze-fracture replica labeling. (2005)
  • Author(s): Hagiwara A
  • Journal Title: J Comp Neurol (in press)
• [Journal Article] Immunohistochemical localization of Ih channel subunits, HCN1-4 in the rat brain. (2004)
  • Author(s): Notomi T
  • Journal Title: J Comp Neurol 471 Pages: 241-276
• [Presentation] An in vitro screening method for optimal affinity tagging neurotransmitter receptors (2008)
  • Author(s): M. Sumegi
  • Organizer: IBRO International Workshop
  • Place of Presentation: Debrecen
• [Presentation] Differential expression patterns of K+/Cl-co-transporter(KCC2)in neurons within the superficial spinal dorsal horn of rats (2008)
  • Author(s): D. Muszil
  • Organizer: IBRO International Workshop
  • Place of Presentation: Debrecen
• [Presentation] Numbers, densities and co-localization of AMPA-and NMDA-type gluta mate receptors at individual synaptic contact areas in thesuperficial spinal dorsal horn of rats (2007)
  • Author(s): M. ANTAL
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-07
• [Presentation] Differential compartmentalization of GABAB receptor subtypes at mossy-fiber CA3 pyramidal neuron synapses (2007)
  • Author(s): N. GUETG
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-06
• [Presentation] Intrasynaptic enrichment of mGlul receptors in GABAergic synapses asrevealed by SDS-digested freeze-fracture replica labeling (2007)
  • Author(s): F. FERRAGUTI
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-06
• [Presentation] 小脳シナプス可塑性の超微形態基盤 (2007)
  • Author(s): 重本隆一
  • Organizer: 第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会 合同大会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-09-12
• [Presentation] 意識の維持とグルタミン酸受容体の関わり (2007)
  • Author(s): 重本隆一
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2007-05-31
• [Publications] Notomi, Shigemoto: "Immunohistochemical localization of I_h channel subunits, HCN1-4,in the rat brain"Journal of Comparative Neurology. 471(3). 241-276 (2004)