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

Neuron. 2008 Jul 10;59(1):84-97. doi: 10.1016/j.neuron.2008.05.014.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biotinylation / methods
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism*
  • Electric Stimulation
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / biosynthesis
  • Hippocampus / cytology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Patch-Clamp Techniques
  • Protein Biosynthesis / physiology*
  • Rats
  • Receptors, AMPA / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Transfection


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Receptors, AMPA
  • activity regulated cytoskeletal-associated protein
  • Green Fluorescent Proteins
  • Methoxyhydroxyphenylglycol
  • glutamate receptor ionotropic, AMPA 1
  • 3,4-dihydroxyphenylglycol