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

Aryeh Routtenberg, Jerome L. Rekart

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)12-19
Number of pages8
JournalTrends in Neurosciences
Issue number1
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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