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SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons

Academic Article
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Overview

authors

  • Rumbaugh, Gavin
  • Adams, J. P.
  • Kim, J. H.
  • Huganir, R. L.

publication date

  • March 2006

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Silent synapses, or excitatory synapses that lack functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), are thought to be critical for regulation of neuronal circuits and synaptic plasticity. Here, we report that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse number, and excitatory synaptic transmission in hippocampal and cortical cultured neurons. Overexpression of SynGAP in neurons results in a remarkable depression of AMPAR-mediated miniature excitatory postsynaptic currents, a significant reduction in synaptic AMPAR surface expression, and a decrease in the insertion of AMPARs into the plasma membrane. This change is specific for AMPARs because no change is observed in synaptic NMDA receptor expression or total synapse density. In contrast to these results, synaptic transmission is increased in neurons from SynGAP knockout mice as well as in neuronal cultures treated with SynGAP small interfering RNA. In addition, activation of the extracellular signal-regulated kinase, ERK, is significantly decreased in SynGAP-overexpressing neurons, whereas P38 mitogen-activated protein kinase (MAPK) signaling is potentiated. Furthermore, ERK activation is up-regulated in neurons from SynGAP knockout mice, whereas P38 MAPK function is depressed. Taken together, these data suggest that SynGAP plays a critical role in the regulation of neuronal MAPK signaling, AMPAR membrane trafficking, and excitatory synaptic transmission.

subject areas

  • Animals
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases
  • Mutation
  • Neurons
  • Protein Transport
  • Rats
  • Receptors, AMPA
  • Synapses
  • Synaptic Transmission
  • p38 Mitogen-Activated Protein Kinases
  • ras GTPase-Activating Proteins
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Research

keywords

  • glutamate
  • plasticity
  • ras
  • receptor
  • trafficking
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Identity

PubMed Central ID

  • PMC1450173

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0600084103

PubMed ID

  • 16537406
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Additional Document Info

start page

  • 4344

end page

  • 4351

volume

  • 103

issue

  • 12

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