Post-translational protein modification as the substrate for long-lasting memory.
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.
Routtenberg
Aryeh
A
Department of Psychology, Northwestern University, Evanston, IL 60208, USA. aryeh@northwestern.edu
Rekart
Jerome L
JL
D000818:Animals; D006801:Humans; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D009419:Nerve Tissue Proteins