Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate

被引：382

作者：

Waung, Maggie W. ^{[1
]}

Pfeiffer, Brad E. ^{[1
]}

Nosyreva, Elena D. ^{[1
]}

Ronesi, Jennifer A. ^{[1
]}

Huber, Kimberly M. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA

来源：

NEURON | 2008年 / 59卷 / 01期

关键词：

D O I：

10.1016/j.neuron.2008.05.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Salient stimuli that modify behavior induce transcription of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and transport Arc mRNA into dendrites, suggesting that local Arc translation mediates synaptic plasticity that encodes such stimuli. Here, we demonstrate that long-term synaptic depression (LTD) in hippocampal neurons induced by group 1 metabotropic glutamate receptors (mGluRs) relies on rapid translation of Arc. mGluR-LTD induction causes long-term increases in AMPA receptor endocytosis rate and dendritic synthesis of Arc, a component of the AMPAR endocytosis machinery. Knockdown of Arc prevents mGluRs from triggering AMPAR endocytosis or LTD, and acute blockade of new Arc synthesis with antisense oligonucleotides blocks mGluR-LTD and AMPAR trafficking. In contrast, LTD induced by NMDA receptors does not persistently alter AMPAR endocytosis rate, induce Arc synthesis, or require Arc protein. These data demonstrate a role for local Arc synthesis specifically in mGluR-LTD and suggest that mGluR-LTD may be one consequence of Arc mRNA induction during experience.

引用

页码：84 / 97

页数：14

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