Cited by 474Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

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

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Waung, Maggie W., Pfeiffer, Brad E., Nosyreva, Elena D., Ronesi, Jennifer A., Huber, Kimberly M.·2008·Neuron

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.

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Authors
Waung, M. W., Pfeiffer, B. E., Nosyreva, E. D., Ronesi, J. A., & Huber, K. M.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Huber, Kimberly M.
Venue
Neuron
Publisher
Elsevier BV
Published
2008-07
Volume
59
Issue
1
Pages
84-97
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2030040408
Cited by
474
References
56
Citations by year
2026: 6 · 2025: 12 · 2024: 18 · 2023: 14 · 2022: 23 · 2021: 27 · 2020: 28 · 2019: 26 · 2018: 27 · 2017: 45 · 2016: 33 · 2015: 27 · 2014: 23 · 2013: 32 · 2012: 33
FWCI
14.42
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • FRAXA Research Foundation
  • National Institutes of Health (1F31NS050992, HD052731, NS045711, T32 GM08014)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
Arc/Arg3.1, local protein synthesis, metabotropic glutamate receptors, long-term depression, AMPA receptor endocytosis, dendritic translation, synaptic plasticity, hippocampal neurons, AMPA receptor trafficking, activity-regulated cytoskeleton-associated protein
MeSH terms
Analysis of Variance, Animals, Animals, Newborn, Cells, Cultured, Cytoskeletal Proteins, Electric Stimulation, Endocytosis, Gene Expression Regulation, Hippocampus, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Synaptosomes, Transfection, Protein Biosynthesis, Long-Term Potentiation, Receptors, AMPA, Patch-Clamp Techniques, Biotinylation, Oligodeoxyribonucleotides, Antisense, Green Fluorescent Proteins, Mice, Rats, In Vitro Techniques

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