Fear extinction requires Arc/Arg3.1 expression in the basolateral amygdala

Mol Brain. 2014 Apr 23:7:30. doi: 10.1186/1756-6606-7-30.


Background: Prolonged re-exposure to a fear-eliciting cue in the absence of an aversive event extinguishes the fear response to the cue, and has been clinically used as an exposure therapy. Arc (also known as Arg3.1) is implicated in synaptic and experience-dependent plasticity. Arc is regulated by the transcription factor cAMP response element binding protein, which is upregulated with and necessary for fear extinction. Because Arc expression is also activated with fear extinction, we hypothesized that Arc expression is required for fear extinction.

Findings: Extinction training increased the proportion of Arc-labeled cells in the basolateral amygdala (BLA). Arc was transcribed during latter part of extinction training, which is possibly associated with fear extinction, as well as former part of extinction training. Intra-BLA infusions of Arc antisense oligodeoxynucleotide (ODN) before extinction training impaired long-term but not short-term extinction memory. Intra-BLA infusions of Arc antisense ODN 3 h after extinction training had no effect on fear extinction.

Conclusion: Our findings demonstrate that Arc is required for long-term extinction of conditioned fear and contribute to the understanding of extinction as a therapeutic manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Conditioning, Psychological
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Early Growth Response Protein 1 / metabolism
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • Fear / drug effects
  • Fear / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Protein Biosynthesis / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Time Factors
  • Transcription, Genetic / drug effects
  • Up-Regulation / drug effects


  • Cytoskeletal Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-fos
  • activity regulated cytoskeletal-associated protein