Prefrontal Cortical NR2B-Containing NMDA Receptors are Essential for Spatial Working Memory Performance

Abstract NR2A and NR2B are the major GluR2 subunits of N-methyl-D-aspartate (NMDA) receptor. NR2B-containing NMDA receptor was found exclusively expressed in prefrontal cortical (PFC) layer III post-synapses of pyramidal neurons. Many studies have suggested the importance of PFC NR2B-containing NMDA receptor for working memory, especially for the persistent delay cell firing. However, direct evidence for the necessity of PFC NR2B-containing NMDA receptor on working memory is still absent, especially in non-human primates. Here, we directly evaluated the necessity of PFC synaptic NR2B in both rats and monkeys. We first examined the synaptosome expression ratio of NR2B/2A in the PFC, hippocampus and visual cortex and confirmed a relatively higher expression ratio in the PFC than in the hippocampus and visual cortex in both species. We then investigated the effect of intra-PFC blockade of NR2B on the performance of spatial working memory task and found that the spatial working memory, but not pattern discrimination, was robustly impaired in a delay length-dependent way upon NR2B blockade in both species. The present study provided behavioral and neuropharmacological evidence for the critical role of PFC NR2B-containing receptor in primate PFC.