Hippocampal N-methyl-D-aspartate receptor-mediated encoding and retrieval processes in spatial working memory: delay-interposed radial maze performance in rats.

In order to clarify the role of hippocampal N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in different stages of spatial working memory, we first assessed the rats' performance in a delay-interposed eight-arm radial maze task (experiment 1). When a delay was interposed after the first four correct choices, rats showed more errors in the second-half performance depending on the length of delay; however, they did not show any significant increase of error choices until the delay was beyond 2 h. We then tested the effect of 2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX)-disodium, an AMPA receptor antagonist, on a standard (no delay-interposed) radial maze task (experiment 2). The drug effect was maintained 15-30 min but it completely disappeared 60 min after dorsal hippocampal microinjection. Based on these findings we finally investigated the effects of hippocampal AP5 and NBQX administered at different stages of 2 h delay-interposed radial maze task on the second-half performance (experiment 3). AP5 immediately before the first-half and before the second-half performance significantly impaired the correct choices, but the treatment immediately after the first-half performance did not, while NBQX impaired them in all three conditions. Results suggest that hippocampal NMDA receptors play an important role in encoding and retrieval processes of spatial working memory, while AMPA receptor activation is necessary not only in these processes but also in consolidation/retention process.