[An animal model of human declarative (relational) memory and of its dysfunction]

The present work was aimed at determining, both at the psychological and at the neurobiological levels, aspects of rodent memory that fall into line with human declarative memory which is known to be selectively impaired in amnesic subjects and during the course of ageing. The ability to compare and to contrast items in memory, and to support inferential use of memories in novel situations (flexibility), were considered to be the two key psychological features of human declarative memory that were altered by both hippocampal lesions and hippocampal dysfunction. Adult and aged mice were trained on learning tasks using two-stage paradigms, the aim of which was to assess memory performance through these two psychological aspects in the same subjects. Results suggest that ageing specifically impairs the ability to both compare and contrast items in memory (declarative/relational memory based on complex associations), without altering memory based on simple S-R associations (procedural memory). Hippocampal lesions in adult mice produced the same dissociation between relational memory (impaired) and procedural memory (spared). Pharmacological experiments showed that, depending on the drug used, the relational memory deficit of aged mice may be selectively reversed (i.e. without changes in procedural memory) and that the behavioural efficacy of certain treatments was shown to parallel their potency in re-establishing normal (i.e. adult) levels of hippocampal plasticity-related mechanisms. Together with previous findings, these results suggest that the storage and use of relational representations would critically depend on the plasticity of hippocampal synapses, which via their connections with cortical areas, would support the storage of associations between perceptual, behavioral and cognitive events.