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Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR

Maggie W Waung1, Brad E Pfeiffer, Elena D Nosyreva

  • 1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Neuron
|July 11, 2008
PubMed

Insights

Activity-regulated cytoskeleton-associated protein (Arc) is crucial for long-term synaptic depression (LTD) in hippocampal neurons. Rapid Arc translation is essential for metabotropic glutamate receptor-induced LTD, but not NMDA receptor-induced LTD.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Plasticity

Background:

  • Salient stimuli trigger activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) transcription and dendritic mRNA transport.
  • Local Arc translation is hypothesized to mediate synaptic plasticity encoding stimuli.

Purpose of the Study:

  • To investigate the role of Arc translation in long-term synaptic depression (LTD) induced by different receptors.
  • To determine if Arc synthesis is specifically required for metabotropic glutamate receptor (mGluR)-LTD.

Main Methods:

  • Utilized hippocampal neurons.
  • Employing knockdown techniques and antisense oligonucleotides to block Arc synthesis.
  • Investigated AMPA receptor endocytosis rates and Arc synthesis during LTD.

Main Results:

  • Long-term synaptic depression (LTD) induced by group 1 metabotropic glutamate receptors (mGluRs) depends on rapid Arc translation.
  • mGluR-LTD induction increases AMPA receptor endocytosis and dendritic Arc synthesis.
  • Arc knockdown or synthesis blockade prevents mGluR-LTD and AMPA receptor trafficking.
  • NMDA receptor-induced LTD does not require persistent changes in AMPA receptor endocytosis or Arc synthesis.

Conclusions:

  • Local Arc synthesis is specifically required for mGluR-LTD in hippocampal neurons.
  • mGluR-LTD may be a direct consequence of experience-induced Arc mRNA translation.

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