Rapid Translation of Arc/Arg3.1 Selectively Mediates mGluR-Dependent LTD through Persistent Increases in AMPAR Endocytosis Rate

Maggie W. Waung, Brad E. Pfeiffer, Elena D. Nosyreva, Jennifer A. Ronesi, Kimberly M. Huber

Research output: Contribution to journalArticlepeer-review

320 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)84-97
Number of pages14
JournalNeuron
Volume59
Issue number1
DOIs
StatePublished - Jul 10 2008

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Rapid Translation of Arc/Arg3.1 Selectively Mediates mGluR-Dependent LTD through Persistent Increases in AMPAR Endocytosis Rate'. Together they form a unique fingerprint.

Cite this