Activation of extracellular signal-regulated kinase-mitogen-activated protein kinase cascade in the amygdala is required for memory reconsolidation of auditory fear conditioning

Sevil Duvarci, Karim Nader, Joseph E. LeDoux

Research output: Contribution to journalArticle

Abstract

Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in the lateral nucleus of amygdala (LA). Recently we have demonstrated that consolidated fear memories, when reactivated, return to a labile state which is sensitive to disruption by the protein synthesis inhibitor anisomycin. The specific molecular mechanisms that underlie this reconsolidation of fear memories are still largely unknown. The activation of extracellular signal-regulated kinase-mitogen-activated protein kinase (ERK-MAPK) pathway in the LA is required for the consolidation of auditory fear memories. In the present study, we examined the role of ERK-MAPK cascade in the LA during reconsolidation of auditory fear conditioning. We show that intra-LA infusions of the MAPK kinase (MEK) inhibitor U0126, a manipulation which inhibits activation of ERK-MAPK, impairs postreactivation long-term memory (PR-LTM) but leaves the postreactivation short-term memory (PR-STM) intact. The same treatment with U0126, in the absence of memory reactivation, has no effect. Furthermore, we verified that reconsolidation requires translation using a second protein synthesis inhibitor, cycloheximide. Post-reactivation infusions of cycloheximide blocked PR-LTM but not PR-STM and, in the absence of reactivation, had no effect. Our data show that activation of ERK-MAPK signalling pathway and protein synthesis in the LA are required for reconsolidation of auditory fear memories.

Original languageEnglish (US)
Pages (from-to)283-289
Number of pages7
JournalEuropean Journal of Neuroscience
Volume21
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Anisomycin
  • Cycloheximide
  • ERK-MAPK

ASJC Scopus subject areas

  • Neuroscience(all)

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