ERK-associated changes of AP-1 proteins during fear extinction

Anita L. Guedea, Christina Schrick, Yomayra F. Guzman, Katie Leaderbrand, Vladimir Jovasevic, Kevin A. Corcoran, Natalie C. Tronson, Jelena Radulovic

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Extensive research has unraveled the molecular basis of learning processes underlying contextual fear conditioning, but the mechanisms of fear extinction remain less known. Contextual fear extinction occurs when an aversive stimulus that initially caused fear is no longer present and depends on the activation of the extracellular signal-regulated kinase (ERK), among other molecules. Here we investigated how ERK signaling triggered by extinction affects its downstream targets belonging to the activator protein-1 (AP-1) transcription factor family. We found that extinction, when compared to conditioning of fear, markedly enhanced the interactions of active, phospho-ERK (pERK) with c-Jun causing alterations of its phosphorylation state. The AP-1 binding of c-Jun was decreased whereas AP-1 binding of JunD, Jun dimerization protein 2 (JDP2) and ERK were significantly enhanced. The increased AP-1 binding of the inhibitory JunD and JDP2 transcription factors was paralleled by decreased levels of the AP-1 regulated proteins c-Fos and GluR2. These changes were specific for extinction and were MEK-dependent. Overall, fear extinction involves ERK/Jun interactions and a decrease of a subset of AP-1-regulated proteins that are typically required for fear conditioning. Facilitating the formation of inhibitory AP-1 complexes may thus facilitate the reduction of fear.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume47
Issue number2
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • C-Fos
  • C-Jun
  • Extinction
  • Fear conditioning
  • Hippocampus
  • JDP2 context
  • JunD

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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