Post-translational protein modification as the substrate for long-lasting memory

Trends Neurosci. 2005 Jan;28(1):12-9. doi: 10.1016/j.tins.2004.11.006.

Abstract

Prevailing models of memory identify mRNA translation as necessary for long-lasting information storage. However, there are enough instances of memory storage in the virtual absence of protein synthesis to prompt consideration of alternative models. A comprehensive review of the protein synthesis literature leads us to conclude that the translational mechanism is exclusively a permissive, replenishment step. Therefore, we propose that post-translational modification (PTM) of proteins already at the synapse is the crucial instructive mechanism underlying long-lasting memory. A novel feature of this model is that non-random spontaneous (or endogenous) brain activity operates as a regulated positive-feedback rehearsal mechanism, updating network configurations by fine-tuning the PTM state of previously modified proteins. Synapses participating in memory storage are therefore supple, a feature required for networks to alter complexity and update continuously. In analogy with codons for amino acids, a long-lasting memory is represented by a 'degenerate code' - a set of pseudo-redundant networks that can ensure its longevity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Memory / physiology*
  • Models, Neurological
  • Nerve Tissue Proteins / metabolism*
  • Protein Biosynthesis / physiology
  • Protein Processing, Post-Translational / physiology*
  • Synaptic Transmission / physiology*

Substances

  • Nerve Tissue Proteins