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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Biotinylation / methods
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Cells, Cultured
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Cytoskeletal Proteins / metabolism*
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Electric Stimulation
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Endocytosis / drug effects
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Endocytosis / physiology*
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Gene Expression Regulation / drug effects
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Green Fluorescent Proteins / biosynthesis
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Hippocampus / cytology
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In Vitro Techniques
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Methoxyhydroxyphenylglycol / analogs & derivatives
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Methoxyhydroxyphenylglycol / pharmacology
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Mice
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Mice, Inbred C57BL
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Nerve Tissue Proteins / metabolism*
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Neurons / drug effects
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Neurons / physiology*
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Neurons / ultrastructure
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Patch-Clamp Techniques
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Protein Biosynthesis / physiology*
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Rats
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Receptors, AMPA / metabolism*
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Transfection
Substances
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Cytoskeletal Proteins
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Nerve Tissue Proteins
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Oligodeoxyribonucleotides, Antisense
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Receptors, AMPA
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activity regulated cytoskeletal-associated protein
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Green Fluorescent Proteins
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Methoxyhydroxyphenylglycol
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glutamate receptor ionotropic, AMPA 1
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3,4-dihydroxyphenylglycol