Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala

Eur J Neurosci. 2001 Apr;13(7):1453-8. doi: 10.1046/j.0953-816x.2001.01531.x.


Fear memory retrieval has been shown to induce a protein-synthesis dependent re-consolidation of memories within the amygdala. Here, using immunocytochemistry, we investigated the molecular basis of this process in the rat and show that retrieval of a cued fear memory induces the activation, by phosphorylation, of the transcription factor CREB within the basal and lateral nuclei of the amygdala, as well as expression of the CREB-regulated immediate-early gene, c-fos, in the basal amygdala. We also show an increase in CREB phosphorylation within the central nucleus of the amygdala following behavioural testing, with an accompanying increase in Fos-immunoreactive nuclei in animals retrieving the cued association. There were no changes in either phosphorylated CREB or Fos in the hippocampus following exposure to discrete fear stimuli. These results show that activation of CREB, which has been shown to be involved in the formation of long-term fear memories, also accompanies memory retrieval, and also suggest a role for CREB phosphorylation in memory re-consolidation following retrieval.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / chemistry
  • Amygdala / metabolism*
  • Animals
  • Antibodies
  • Conditioning, Psychological / physiology
  • Cyclic AMP Response Element-Binding Protein / analysis
  • Cyclic AMP Response Element-Binding Protein / immunology
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Electroshock
  • Fear / physiology*
  • Hippocampus / chemistry
  • Hippocampus / metabolism
  • Male
  • Memory / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / immunology
  • Rats
  • Rats, Inbred Strains


  • Antibodies
  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-fos