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

Paired-associate learning is often used to examine episodic memory in humans1. Animal models include the recall of food-cache locations by scrub jays2 and sequential memory3,4. 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 plasticity5,6—impaired memory encoding but had no effect on recall. Inactivating hippocampal neural activity by blocking α-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 space7,8, with consolidation of the memory traces representing repeated paired associates in circuits elsewhere.