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Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission

Academic Article
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Overview

authors

  • Verde, E. M. R.
  • Lee-Osbourne, J.
  • Worley, P. F.
  • Malinow, R.
  • Cline, Hollis

publication date

  • November 2006

journal

  • Neuron  Journal

abstract

  • Arc/Arg3.1 is an immediate-early gene whose expression levels are increased by strong synaptic activation, including synapse-strengthening activity patterns. Arc/Arg3.1 mRNA is transported to activated dendritic regions, conferring the distribution of Arc/Arg3.1 protein both temporal correlation with the inducing stimulus and spatial specificity. Here, we investigate the effect of increased Arc/Arg3.1 levels on synaptic transmission. Surprisingly, Arc/Arg3.1 reduces the amplitude of synaptic currents mediated by AMPA-type glutamate receptors (AMPARs). This effect is prevented by RNAi knockdown of Arc/Arg3.1, by deleting a region of Arc/Arg3.1 known to interact with endophilin 3 or by blocking clathrin-coated endocytosis of AMPARs. In the hippocampal slice, Arc/Arg3.1 results in removal of AMPARs composed of GluR2 and GluR3 subunits (GluR2/3). Finally, Arc/Arg3.1 expression occludes NMDAR-dependent long-term depression. Our results demonstrate that Arc/Arg3.1 reduces the number of GluR2/3 receptors leading to a decrease in AMPAR-mediated synaptic currents, consistent with a role in the homeostatic regulation of synaptic strength.

subject areas

  • Animals
  • Animals, Newborn
  • Biotinylation
  • Blotting, Western
  • Cytoskeletal Proteins
  • Electric Stimulation
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Gene Expression
  • Green Fluorescent Proteins
  • Hippocampus
  • In Vitro Techniques
  • Long-Term Synaptic Depression
  • Models, Biological
  • Mutagenesis
  • N-Methylaspartate
  • Nerve Tissue Proteins
  • Neurons
  • Okadaic Acid
  • Patch-Clamp Techniques
  • RNA Interference
  • Rats
  • Receptors, AMPA
  • Statistics, Nonparametric
  • Synaptic Transmission
  • Time Factors
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Identity

PubMed Central ID

  • PMC3951199

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2006.09.031

PubMed ID

  • 17088212
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Additional Document Info

start page

  • 461

end page

  • 474

volume

  • 52

issue

  • 3

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