2003 Fiscal Year Annual Research Report

異種シナプス間競合原理に基づく小脳神経回路発達の分子機構

Research Project

Project/Area Number	14208091
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)	狩野方伸金沢大学, 大学院・医学研究科, 教授 (40185963) 深谷昌弘北海道大学, 大学院・医学研究科, 助手 (10360900)
Keywords	小脳 / プルキンエ細胞 / カルシウムチャネル / 平行線維 / 登上線維 / シナプス形成 / P / Q型
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、協調運動や運動学習機能において中心的役割を果たしている。これまで、我々は、その処理基盤となる平行線維・プルキンエ細胞間シナプスに特異的なグルタミン酸受容体GluRδ2を欠失する遺伝子ノックアウトマウスの回路解析を行なってきた。その結果、GluRδ2の欠失により、遠位樹状突起における平行線維とプルキンエ細胞スパインとの間のシナプス形成率が低下して多数のフリースパインが生じ、プルキンエ細胞当たりの平行線維シナプスは約半分にまで減少した。さらに、登上線維の支配にも遠位拡大化が二次的に誘導され、これが周囲のプルキンエ細胞の遠位樹状突起にも波及することにより、遠位型の多重支配が生じることを明らかにした。これらの事実は、GluRδ2が平行線維側の強化分子として平行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示している。本年度は、これと拮抗する登上線維側の強化分子機構として、登上線維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α1Aに着目した。α1A欠損マウスでは、登上線維支配の近位退縮化が生じ、樹状突起の基部および細胞体に対する近位重複型の多重支配が生じた。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。以上の結果より、プルキンエ細胞のシナプス形成は異種入力線維間の激しい競合を基盤として発達することを示しており、これがそれぞれ入力線維に特異な強化分子機構に立脚していることを物語っている。NMDA型グルタミン酸受容体を介するカルシウム流入は、臨界期における体性感覚野や視覚野での競合的シナプス改築を制御していることが広く知られている。我々の研究成果は、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 ASCT1 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 in targeted 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-Purkinje cell 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 endoneuriai 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+> channel α1A regulates synaptic competition on developing cerebellar Purkinje cells"J.Neurosci.. (印刷中).

2003 Fiscal Year Annual Research Report

異種シナプス間競合原理に基づく小脳神経回路発達の分子機構

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 ASCT1 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 in targeted 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-Purkinje cell 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 endoneuriai 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+> channel 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)