Glutamate-receptor-mediated encoding and retrieval of paired-associate learning

Paired-associate learning is often used to examine episodic memory in humans(1). Animal models include the recall of food-cache locations by scrub jays(2) and sequential memory(3,4). Here we report a model in which rats encode, during successive sample trials, two paired associates ( flavours of food and their spatial locations) and display better-than-chance recall of one item when cued by the other. In a first study, pairings of a particular foodstuff and its location were never repeated, so ensuring unique 'what-where' attributes. Blocking N-methyl-D-aspartate receptors in the hippocampus - crucial for the induction of certain forms of activity-dependent synaptic plasticity(5,6) impaired memory encoding but had no effect on recall. Inactivating hippocampal neural activity by blocking alpha-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid ( AMPA) receptors impaired both encoding and recall. In a second study, two paired associates were trained repeatedly over 8 weeks in new pairs, but blocking of hippocampal AMPA receptors did not affect their recall. Thus we conclude that unique what - where paired associates depend on encoding and retrieval within a hippocampal memory space(7,8), with consolidation of the memory traces representing repeated paired associates in circuits elsewhere.