Enhancement of fear memory by retrieval through reconsolidation

Elife. 2014 Jun 24:3:e02736. doi: 10.7554/eLife.02736.

Abstract

Memory retrieval is considered to have roles in memory enhancement. Recently, memory reconsolidation was suggested to reinforce or integrate new information into reactivated memory. Here, we show that reactivated inhibitory avoidance (IA) memory is enhanced through reconsolidation under conditions in which memory extinction is not induced. This memory enhancement is mediated by neurons in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) through the simultaneous activation of calcineurin-induced proteasome-dependent protein degradation and cAMP responsive element binding protein-mediated gene expression. Interestingly, the amygdala is required for memory reconsolidation and enhancement, whereas the hippocampus and mPFC are required for only memory enhancement. Furthermore, memory enhancement triggered by retrieval utilizes distinct mechanisms to strengthen IA memory by additional learning that depends only on the amygdala. Our findings indicate that reconsolidation functions to strengthen the original memory and show the dynamic nature of reactivated memory through protein degradation and gene expression in multiple brain regions.DOI: http://dx.doi.org/10.7554/eLife.02736.001.

Keywords: amygdala; cAMP responsive element binding protein; enhancement; fear memory; proteasome-dependent protein degradation; reconsolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Calcineurin / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Fear / physiology*
  • Gene Expression
  • Hippocampus / metabolism
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Phosphorylation
  • Prefrontal Cortex / metabolism
  • Promoter Regions, Genetic
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-fos
  • Calcineurin
  • Proteasome Endopeptidase Complex

Grants and funding

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.