グルタミン酸シグナル伝達機構によるマウス体性感覚野バレルの臨界期発達

2006 Fiscal Year Annual Research Report

• Project/Area Number: 17300108
• 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)
• Keywords: グルタミン酸 / 受容体 / バレル / 可塑性 / 臨界期

Research Abstract

本研究では、遺伝子改変マウスを用いて、大脳皮質体性感覚野における臨界期の時間特性と可塑性振幅を制御する分子機構の解明を目的とする。特に、シナプス回路発達の最も重要な鍵を握っているNMDA型グルタミン酸受容体で発達段階の主要な発現サブユニットであるGluRε2とGluRε4と、大脳皮質の主要なグルタミン酸トランスポーターであるGLTlとGLASTに焦点を当て、これらの欠損マウスにおける臨界期の開始/終了時期と臨界期可塑性の振幅について検討した。
その結果、野生型マウスに比べ、NMDA受容体GluRε1遺伝子を1個欠くヘテロマウスではバレルの出現と臨界期の終了時期がともに1日遅れ、GluRε4遺伝子を完全に欠失するホモマウスでは1日速まっていることが判明した。一方、C列触覚毛除去による臨界期可塑性の振幅は変化しなかった。一方、GLT1欠損マウスとGLAST欠損マウスでは、バレルの出現時期や臨界期の終了時期に違いは見られなかったが、C列触覚毛除去後のC列バレルの縮小率とB/Dバレルの拡大率が共に縮小し臨界期可塑性振幅が減少していた。これらの結果から、NMDA受容体はバレルの形成発達の時間的制御に関与し、グルタミン酸トランスポーターは活動依存的な臨界期可塑性振幅の制御に中心的な役割を果たしていることを示している。従って、両者の分子機構が揃うことにより、競合的なシナプス回路の臨界期発達が正常に行われることを物語っている。

Research Products

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