1996 Fiscal Year Annual Research Report

長期抑制制御分子と小脳シナプス形成機構に関する分子神経解剖学的研究

Research Project

Project/Area Number	08680805
Research Institution	Hokkaido University
Principal Investigator	渡辺雅彦北海道大学, 医学部, 助教授 (70210945)
Keywords	グルタミン酸受容体 / グルタミン酸トランスポーター / ノックアウトマウス / 小脳 / プルキン工細胞 / 平行線維 / 登上線維
Research Abstract	小脳長期抑制は、登上線維/プルキンエ細胞間シナプスおよび平行線維/プルキンエ細胞巻シナプスにおける神経伝達活動に依存して生ずるシナプス可塑性現象で、運動学習の基盤と考えられている。本研究では、小脳長期抑制に関与している1)イオンチャネル型グルタミン酸受容体δ2サブユニット、2)代謝型グルタミン酸受容体mGluR1、3)蛋白リン酸化酵素PKCγの3種の機能分子に注目して、プルキンエ細胞におけるこれらの分子の発現局在と分子欠損に伴うシナプス形成異常を分子神経解剖学的観点から解析を行った。その結果、δ2サブユニットは胎生期から成熟期に至るまで小脳プルキンエに特異的に発現する分子であることが判明した。その遺伝子ノックアウトは、平行線維シナプスの著明な減少をもたらし、登上線維の成熟が阻害され、小脳長期抑制現象が消失し、運動学習に障害が生じた。これに対して、プルキンエ細胞に高濃度に発現することが知られているmGluR1およびRKCγの分子欠損は、平行線維シナプスの形成には影響を及ぼさなかったが、登上線維シナプスの成熟が著しく阻害され、長期抑制現象が消失し、運動学習に障害が生じた。これらの事実は、イオンチャネル型のグルタミン酸と代謝型グルタミン酸カスケードがシナプスの成熟と可塑性に対して重要な役割を果たしているが、シナプス形成に対する寄与という点ではそれぞれの分子機構が異なる役割を担っていることを示唆している。

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] Ito,Isao: "Synapse-selective impaiment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J. Physiol.(印刷中).
[Publications] Yamada,Keiko: "Changes in expression and distribution of the glutamate transporter EAAT4 in developing mouse Purkinje cells." Neurosi. Res.(印刷中).
[Publications] Kano,Masanobu: "Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1" Neuron. (印刷中).
[Publications] Watanabe,Masahiko: "Modified expression of the N-methyl-D-aspartate receptor subunit emerges in reeler Purkinie cels after establishment of the adult wild-type expression." Neurosci. Res.26. 335-343 (1996)
[Publications] Watanabe,Masahiko: "Developmental dynamics of gene expression for NMDA receptor channel." In : The Ionotropic Glutamate Receptors (eds. Monaghan, DT. and Wenthold, R.) Humana Press.189-218 (1996)
[Publications] Nakagawa,Shin: "Altered gene expression of the N-methyl-D-asparate receptor channel subunits in Purkinie cells of the staggerer mutant mouse." Eur. J. Neurosci.8. 2644-2651 (1996)
[Publications] Yamada,Keiko: "EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses." Neuroreport.7. 2013-2017 (1996)
[Publications] Nakagawa,Shin: "Regional variation in expressions of calbindin and inositol 1, 4, 5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse." Eur. J. Neurosci.8. 1401-1407 (1996)
[Publications] Watanabe.Masahiko: "Developmental regulation of ionotropic glutamate receptor gene expression and functional correlations." In : Receptor Dynamics in Neural Development. (ed. Shaw, C) CRC Press.73-89 (1996)
[Publications] Shibata,Takashi: "Dynamic changes in expression of glutamate transporter mRNAs in developing brain." Neuroreport. 7. 705-709 (1996)
[Publications] Kutsuwada,Tatsuya: "Impairment of suckling repsonse, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. 16. 333-344 (1996)
[Publications] Ido,Akiko: "Cloning of the cDNA encoding the mouse ATBF1 transcription factor." Gene. 168. 227-231 (1996)
[Publications] Takayama,Chitoshi: "Developmental changes in expression and distribution of the glutamate receptor channel δ2 subunit according to the Purkinie cel maturation." Dev. Brain Res.92. 147-155 (1996)
[Publications] Kano,Masanobu: "Impaired synapse elimination during cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)

1996 Fiscal Year Annual Research Report

長期抑制制御分子と小脳シナプス形成機構に関する分子神経解剖学的研究

Principal Investigator

渡辺 雅彦 北海道大学, 医学部, 助教授 (70210945)

Research Products

[Publications] Ito,Isao: "Synapse-selective impaiment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J. Physiol.(印刷中).

[Publications] Yamada,Keiko: "Changes in expression and distribution of the glutamate transporter EAAT4 in developing mouse Purkinje cells." Neurosi. Res.(印刷中).

[Publications] Kano,Masanobu: "Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1" Neuron. (印刷中).

[Publications] Watanabe,Masahiko: "Modified expression of the N-methyl-D-aspartate receptor subunit emerges in reeler Purkinie cels after establishment of the adult wild-type expression." Neurosci. Res.26. 335-343 (1996)

[Publications] Watanabe,Masahiko: "Developmental dynamics of gene expression for NMDA receptor channel." In : The Ionotropic Glutamate Receptors (eds. Monaghan, DT. and Wenthold, R.) Humana Press.189-218 (1996)

[Publications] Nakagawa,Shin: "Altered gene expression of the N-methyl-D-asparate receptor channel subunits in Purkinie cells of the staggerer mutant mouse." Eur. J. Neurosci.8. 2644-2651 (1996)

[Publications] Yamada,Keiko: "EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses." Neuroreport.7. 2013-2017 (1996)

[Publications] Nakagawa,Shin: "Regional variation in expressions of calbindin and inositol 1, 4, 5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse." Eur. J. Neurosci.8. 1401-1407 (1996)

[Publications] Watanabe.Masahiko: "Developmental regulation of ionotropic glutamate receptor gene expression and functional correlations." In : Receptor Dynamics in Neural Development. (ed. Shaw, C) CRC Press.73-89 (1996)

[Publications] Shibata,Takashi: "Dynamic changes in expression of glutamate transporter mRNAs in developing brain." Neuroreport. 7. 705-709 (1996)

[Publications] Kutsuwada,Tatsuya: "Impairment of suckling repsonse, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. 16. 333-344 (1996)

[Publications] Ido,Akiko: "Cloning of the cDNA encoding the mouse ATBF1 transcription factor." Gene. 168. 227-231 (1996)

[Publications] Takayama,Chitoshi: "Developmental changes in expression and distribution of the glutamate receptor channel δ2 subunit according to the Purkinie cel maturation." Dev. Brain Res.92. 147-155 (1996)

[Publications] Kano,Masanobu: "Impaired synapse elimination during cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)

渡辺雅彦北海道大学, 医学部, 助教授 (70210945)