Rapid Translation of Arc/Arg3.1 Selectively Mediates mGluR-Dependent LTD through Persistent Increases in AMPAR Endocytosis Rate
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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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ARC is required for mGluR-LTD and AMPAR internalization.
“ARC is required for mGluR-LTD and AMPAR internalization (Waung et al., 2008)”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Waung et al., 2008
Translation of Arc mRNA is enhanced during and crucial for mGluR-dependent LTD.
“Translation of Arc mRNA is enhanced during, and crucial for, mGluR-dependent LTD59,60.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [60]
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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)
- PMC
- PMC2580055
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1878 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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