Activation of silent synapses by rapid activity-dependent synaptic recruitment of AMPA receptors

Dezhi Liao, Robert H. Scannevin, Richard Huganir

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

Abstract

Many recent studies have shown that excitatory synapses can contain NMDA receptor responses in the absence of functional AMPA receptors and are therefore postsynaptically silent at resting membrane potentials. The activation of silent synapses via the rapid acquisition of AMPA receptor responses may be important in synaptic plasticity and neuronal development. Our recent immunocytochemical studies that used cultured hippocampal neurons have provided evidence for "morphological silent synapses" that physically contain NMDA receptors but no AMPA receptors. Here we show that the activation of NMDA receptors by spontaneous synaptic activity results in the rapid recruitment of AMPA receptors into these morphological silent synapses within minutes. In parallel, we find a significant increase in the frequency of AMPA receptor-mediated miniature EPSCs (mEPSCs). NMDA receptor activation also results in a mobilization of calcium/calmodulin (CaM) kinase II to synapses and an increase in the phosphorylation of surface AMPA receptors on the major CaM kinase II phosphorylation site. These results demonstrate that AMPA receptors can be modified and recruited rapidly to silent synapses via the activation of NMDA receptors by spontaneous synaptic activity.

Original languageEnglish (US)
Pages (from-to)6008-6017
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number16
DOIs
StatePublished - Aug 15 2001

Keywords

  • Calcium/calmodulin-dependent protein kinase II
  • GluR1
  • Long-term depression
  • Long-term potentiation
  • Synaptic plasticity
  • mEPSC

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