A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype

Nat Neurosci. 2010 Feb;13(2):223-31. doi: 10.1038/nn.2474. Epub 2009 Dec 27.


Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism
  • Cerebellum / physiology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fear / physiology*
  • Gene Expression Regulation
  • MAP Kinase Signaling System / physiology
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Norepinephrine / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism*
  • Receptors, Adrenergic, beta / metabolism
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism
  • Synapses / physiology*
  • Transcription, Genetic*


  • Calcium Channels, L-Type
  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, Adrenergic, beta
  • Extracellular Signal-Regulated MAP Kinases
  • glutamate receptor ionotropic, AMPA 2
  • Calcium
  • glutamate receptor ionotropic, AMPA 1
  • Norepinephrine