Synaptic protein degradation underlies destabilization of retrieved fear memory

Science. 2008 Feb 29;319(5867):1253-6. doi: 10.1126/science.1150541. Epub 2008 Feb 7.

Abstract

Reactivated memory undergoes a rebuilding process that depends on de novo protein synthesis. This suggests that retrieval is dynamic and serves to incorporate new information into preexisting memories. However, little is known about whether or not protein degradation is involved in the reorganization of retrieved memory. We found that postsynaptic proteins were degraded in the hippocampus by polyubiquitination after retrieval of contextual fear memory. Moreover, the infusion of proteasome inhibitor into the CA1 region immediately after retrieval prevented anisomycin-induced memory impairment, as well as the extinction of fear memory. This suggests that ubiquitin- and proteasome-dependent protein degradation underlies destabilization processes after fear memory retrieval. It also provides strong evidence for the existence of reorganization processes whereby preexisting memory is disrupted by protein degradation, and updated memory is reconsolidated by protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisomycin / pharmacology
  • Conditioning, Psychological
  • Extinction, Psychological
  • Fear*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Lactones / pharmacology
  • Male
  • Memory*
  • Mental Recall*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Synapses / metabolism*
  • Ubiquitination

Substances

  • Lactones
  • Nerve Tissue Proteins
  • Protein Synthesis Inhibitors
  • postsynaptic density proteins
  • clasto-lactacystin beta-lactone
  • Anisomycin
  • Proteasome Endopeptidase Complex