2003 Fiscal Year Annual Research Report

カルシウムシグナリングと小脳シナプス回路発達

Research Project

Project/Area Number	15016001
Research Institution	Hokkaido University
Principal Investigator	渡辺雅彦北海道大学, 大学院・医学研究科, 教授 (70210945)
Co-Investigator(Kenkyū-buntansha)	深谷昌弘北海道大学, 大学院・医学研究科, 助手 (10360900)
Keywords	小脳 / 登上線維 / 平行線維 / シナプス形成 / カルシウムチャネル / プルキンエ細胞 / 発達
Research Abstract	プルキンエ細胞は小脳における主要な情報処理ニューロンで、平行線維と登上線維による興奮性シナプス活動を基盤として協調運動や運動学習機能を発現する。これまでの研究から、平行線維シナプスに特異的なグルタミン酸受容体GluRd2が、遠位樹状突起における平行線維とプルキンエ細胞との間のシナプス形成を強化し、登上線維支配の過度な遠位化を防ぐ分子機構であることを明らかにしてきた。本年度は、登上線維側の強化分子機構を探索する目的で、この活動によりカルシウム流入を誘導するP/Q型カルシウムチャネルalpha-1Aに着目し、その遺伝子欠損マウスの小脳シナプス回路を検討した。その結果、近位樹状突起での登上線維支配の退縮が生じ、樹状突起の基部および細胞体において複数の登上線維による多重支配が生じた。一方、平行線維は本来の遠位樹状突起にとどまらず、近位樹状突起から細胞体にまで支配が拡大していた。以上の結果は、alpha-1Aが登上線維側の分子機構としてこのシナプス基盤を強化し、平行線維支配の過度な近位化を防御していることを示している。さらに、この分子欠損に伴なう樹状突起基部と細胞体における平行線維シナプスと登上線維シナプスの混在化は、この分子が主要な登上線維による独占的なシナプス支配に寄与し、そのコンパートメントからそれ以外の登上線維と平行線維による支配を排除していることも示している。この研究成果は、競合的な神経活動に伴うカルシウム流入が、視覚野や体性感覚野などの大脳皮質だけでなく、小脳における機能的シナプス回路成熟にも重要な鍵となっていることを示している。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Sakai, K.: "Neutral amino acid transporter ASOT1 is preferentially expressed in L-Ser-synthetic/storing glial cells in the mouse with transient expression in developing capillaries."J.Neurosci.. 23. 550-560 (2003)
[Publications] Kakizawa, S.: "Effects of Insulin-like Growth Factor I on Climbing Fiber Synapse Elimination during Cerebellar Development."Eur.J.Neurosci. 17. 545-554 (2003)
[Publications] Fukaya, M.: "Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum intargeted NR1 knockout mice."Proc.Natl.Acad.Sci.USA. 100. 4855-4860 (2003)
[Publications] Shibata, T.: "Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord."Dev.Brain Res.. 140. 263-268 (2003)
[Publications] Somogyi, P.: "High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurones in the rat hippocampus."Eur.J.Neurosci.. 17. 2503-2520 (2003)
[Publications] Miyazaki, T.: "Developmental switching of vesicular glutamate transporters at parallel fiber-Purkinjecell synapses."Eur.J.Neurosci. 17. 2563-2572 (2003)
[Publications] Sassoe-Pngnetto, M.: "Organization of postsynaptic density proteins and glutamate receptors in axodendritic and dendrodendritic synapses of the rat olfactory bulb."J.Comp.Neurol.. 463. 237-248 (2003)
[Publications] Miyata, M.: "Role of thalamic phospholipase Cb4 mediated by metabotropic glutamate receptor type 1 in inflammatory pain."J.Neurosci. 23. 8098-8108 (2003)
[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons."Dev.Biol.. 263. 216-230 (2003)
[Publications] Takahashi, Y.: "Autoantibodies to NMDA receptor in patients with chronic formsof epilepsia partialis continua."Neurol.. 61. 891-896 (2003)
[Publications] Yamashita, N.: "Selective expression of L-serine synthetic enzyme 3PGDH in Schwann cells, perineuronal glia, and endoneurial fibroblasts along sciatic nerves and its upregulation after crush injury."Arch.Histol.Cytol.. (印刷中).
[Publications] Hama, K.: "Lysophosphatidic acid and autaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1."J.Biol.Chem.. (印刷中).
[Publications] Ferraguti, F.: "Immunolocalization of metabotropic glutamate receptor 1a (mGluR1a) in distinct classes of interneuron in the CA1 region of the rat hippocampus."Hippocampus. (印刷中).
[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-accociated PDZ proteins in developing cortical neurons."Dev Biol. (印刷中).
[Publications] Kinoshita, N.: "Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes."Genes Cells. (印刷中).
[Publications] Miyazaki, M.: "P/Q-type Ca^<2+> α1A regulates synaptic competition on developing cerebellar Purkinje cells"J.Neurosci.. (印刷中).

2003 Fiscal Year Annual Research Report

カルシウムシグナリングと小脳シナプス回路発達

Principal Investigator

渡辺 雅彦 北海道大学, 大学院・医学研究科, 教授 (70210945)

Research Products

[Publications] Sakai, K.: "Neutral amino acid transporter ASOT1 is preferentially expressed in L-Ser-synthetic/storing glial cells in the mouse with transient expression in developing capillaries."J.Neurosci.. 23. 550-560 (2003)

[Publications] Kakizawa, S.: "Effects of Insulin-like Growth Factor I on Climbing Fiber Synapse Elimination during Cerebellar Development."Eur.J.Neurosci. 17. 545-554 (2003)

[Publications] Fukaya, M.: "Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum intargeted NR1 knockout mice."Proc.Natl.Acad.Sci.USA. 100. 4855-4860 (2003)

[Publications] Shibata, T.: "Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord."Dev.Brain Res.. 140. 263-268 (2003)

[Publications] Somogyi, P.: "High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurones in the rat hippocampus."Eur.J.Neurosci.. 17. 2503-2520 (2003)

[Publications] Miyazaki, T.: "Developmental switching of vesicular glutamate transporters at parallel fiber-Purkinjecell synapses."Eur.J.Neurosci. 17. 2563-2572 (2003)

[Publications] Sassoe-Pngnetto, M.: "Organization of postsynaptic density proteins and glutamate receptors in axodendritic and dendrodendritic synapses of the rat olfactory bulb."J.Comp.Neurol.. 463. 237-248 (2003)

[Publications] Miyata, M.: "Role of thalamic phospholipase Cb4 mediated by metabotropic glutamate receptor type 1 in inflammatory pain."J.Neurosci. 23. 8098-8108 (2003)

[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons."Dev.Biol.. 263. 216-230 (2003)

[Publications] Takahashi, Y.: "Autoantibodies to NMDA receptor in patients with chronic formsof epilepsia partialis continua."Neurol.. 61. 891-896 (2003)

[Publications] Yamashita, N.: "Selective expression of L-serine synthetic enzyme 3PGDH in Schwann cells, perineuronal glia, and endoneurial fibroblasts along sciatic nerves and its upregulation after crush injury."Arch.Histol.Cytol.. (印刷中).

[Publications] Hama, K.: "Lysophosphatidic acid and autaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1."J.Biol.Chem.. (印刷中).

[Publications] Ferraguti, F.: "Immunolocalization of metabotropic glutamate receptor 1a (mGluR1a) in distinct classes of interneuron in the CA1 region of the rat hippocampus."Hippocampus. (印刷中).

[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-accociated PDZ proteins in developing cortical neurons."Dev Biol. (印刷中).

[Publications] Kinoshita, N.: "Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes."Genes Cells. (印刷中).

[Publications] Miyazaki, M.: "P/Q-type Ca^<2+> α1A regulates synaptic competition on developing cerebellar Purkinje cells"J.Neurosci.. (印刷中).

渡辺雅彦北海道大学, 大学院・医学研究科, 教授 (70210945)