A single fear-inducing stimulus induces a transcription-dependent switch in AMPA receptor phenotype

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. Here we show that a single fear-inducing stimulus increases GluR2 mRNA abundance and promotes synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype is mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK /MAPK signaling trigger new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable, to GluR2-containing Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype alters 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.