DNA recombination as a possible mechanism in declarative memory: A hypothesis

The durability of declarative memory suggests that it has either a chemical or a structural basis. Current models of long-term memory are based on the general assumption that traces of memory are stored by structural modifica tions of synaptic connections, resulting in alterations in the patterns of neural activity. Changes in gene expression, regulated at both the transcri ptional and the translational levels, are considered essential for structur al synaptic modifications. Here we present an alternative hypothesis statin g that permanent memory has a chemical rather than a structural basis. We s uggest that the mechanism of memory coding in the brain is similar to that in the immune system so that the permanence of memories in the nervous syst em is ensured at the genomic level by a somatic recombination mechanism. Th us, we hypothesize that traces of permanent declarative memory might presen t within cerebral neurons in the form of novel proteins coded by the modifi ed genes. This discussion is intended to provide evidence in support of a D NA recombination mechanism for memory storage in the brain and to stimulate further research working toward the evaluation of this hypothesis. (C) 200 1 Wiley-Liss, Inc.