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

Yu Liu, Luigi Formisano, Iaroslav Savtchouk, Yukihiro Takayasu, Gábor Szabó, R. Suzanne Zukin, Siqiong June Liu

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalNature Neuroscience
Volume13
Issue number2
DOIs
StatePublished - Feb 18 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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