Journal
NEURON
Volume 59, Issue 1, Pages 84-97Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2008.05.014
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Funding
- NICHD NIH HHS [R01 HD052731-01A2, HD052731, R01 HD052731] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008014, T32 GM08014] Funding Source: Medline
- NINDS NIH HHS [F31 NS050992, NS045711, R01 NS045711, R01 NS045711-06, 1F31NS050992] Funding Source: Medline
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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.
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