The ubiquitin-proteasome system as a critical regulator of synaptic plasticity and long-term memory formation

Neurobiol Learn Mem. 2013 Oct:105:107-16. doi: 10.1016/j.nlm.2013.03.009. Epub 2013 Apr 25.


Numerous studies have supported the idea that de novo protein synthesis is critical for synaptic plasticity and normal long-term memory formation. This requirement for protein synthesis has been shown for several different types of fear memories, exists in multiple brain regions and circuits, and is necessary for different stages of memory creation and storage. However, evidence has recently begun to accumulate suggesting that protein degradation through the ubiquitin-proteasome system is an equally important regulator of memory formation. Here we review those recent findings on protein degradation and memory formation and stability and propose a model explaining how protein degradation may be contributing to various aspects of memory and synaptic plasticity. We conclude that protein degradation may be the major factor regulating many of the molecular processes that we know are important for fear memory formation and stability in the mammalian brain.

Keywords: Consolidation; Fear conditioning; Proteasome; Protein degradation; Reconsolidation; Ubiquitin.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Fear / physiology
  • Memory, Long-Term / physiology*
  • Mice
  • Neuronal Plasticity*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis*
  • Signal Transduction
  • Ubiquitin / metabolism*


  • Ubiquitin
  • Proteasome Endopeptidase Complex