Transgenic inhibition of neuronal protein kinase A activity facilitates fear extinction

Carolina Isiegas, Alice Park, Eric R. Kandel, Ted Abel, K. Matthew Lattal

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Much is known about the neurobiology of memory storage for learned fear. In contrast, the molecular mechanisms underlying extinction of fear memory are just beginning to be delineated. Here, we investigate the role of protein kinase A (PKA) in extinction of memory for contextual fear by using conventional and temporally regulated transgenic approaches that allow us to inhibit PKA activity in neurons within brain regions thought to be involved in extinction. Strikingly, reduction of PKA activity facilitated the development of extinction, without interfering with storage of the original fear memory. Moreover, inhibition of PKA facilitated extinction of both recent and remote contextual fear memories. The finding that PKA, which is required for the acquisition of fear memory, is a constraint for extinction provides the first genetic support for the idea that fear extinction is itself a genuine learning process with its own specific molecular requirements, rather than simply the erasure of a previously learned process. Further, these experiments represent the first genetic evidence that protein kinases may be constraints for the extinction of fear.

Original languageEnglish (US)
Pages (from-to)12700-12707
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number49
DOIs
StatePublished - Dec 6 2006

Keywords

  • Extinction
  • Fear
  • Learning memory
  • Pavlovian conditioning
  • Protein kinase
  • Protein synthesis
  • Reconsolidation
  • Tetracycline
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)

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