グリシン作動性興奮性受容体は対称性と非対称性のどちらのシナプスに発現するか?

• 研究課題/領域番号: 17650087
• 研究種目: 萌芽研究
• 配分区分: 補助金
• 研究分野: 神経科学一般
• 研究機関: 北海道大学
• 研究代表者: 渡辺 雅彦 北海道大学, 大学院医学研究科, 教授 (70210945)
• 研究期間 (年度): 2005 – 2006
• 研究課題ステータス: 完了 (2006年度)
• 配分額: 3,300千円 (直接経費: 3,300千円); 2006年度: 1,600千円 (直接経費: 1,600千円); 2005年度: 1,700千円 (直接経費: 1,700千円)
• キーワード: グルタミン / グリシン / NMDA / シナプス / 興奮性 / 抑制性 / グルタミン酸受容体 / NMDA受容体 / NR3 / 免疫電顕

研究概要

グルタミン酸は脳における主要な興奮性神経伝達物質で、シナプスにおけるグルタミン酸受容体を介してシグナルが伝達される。神経解剖学の重要な基本概念の一つに、「グルタミン酸作動性の興奮性シナプスはシナプス後部の肥厚が著しい非対称性シナプスで、GABAやグリシン作動性の抑制性シナプスは対称性シナプスである」がある。ところが、NMDA型グルタミン酸受容体のNR3サブユニットは、NR1サブユニットと会合してグリシン作動性の興奮性受容体を形成することが報告された。そこで、本研究では、「興奮性-非対称性シナプス/抑制性-対称性シナプス」の原則が正しいのか、「グルタミン酸-興奮性終末/グリシン-抑制性終末」の原則が正しいのかを明らかにする目的で、NR3サブユニットが分布するシナプスの形態学的特徴と神経回路における局在を検討した。この目的達成のため、NR3Aに対する特異抗体を作成したその結果、NR3Aは、小脳では抑制性ニューロンの樹状突起に選択的に発現し、登上線維との間の対称性シナプスと思われる部位に局在していた。一方、登上線維とプルキンエ細胞との間の非対称性シナプスや、平行線維と抑制性ニューロンとの間の非対称性シナプスには存在しなかった。従って、NR3Aはグルタミン酸を放出する神経終末の対称性シナプスに分布し、いずれの原則にも従わないユニークな発現局在をとることが明らかとなった。

研究成果

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