Delay-dependent impairment of spatial working memory with inhibition of NR2B-containing NMDA receptors in hippocampal CA1 region of rats.

Hippocampal N-methyl-D-aspartate receptor (NMDAR) is required for spatial working memory. Although evidence from genetic manipulation mice suggests an important role of hippocampal NMDAR NR2B subunits (NR2B-NMDARs) in spatial working memory, it remains unclear whether or not the requirement of hippocampal NR2B-NMDARs for spatial working memory depends on the time of spatial information maintained. Here, we investigate the contribution of hippocampal NR2B-NMDARs to spatial working memory on delayed alternation task in T-maze (DAT task) and delayed matched-to-place task in water maze (DMP task). Our data show that infusions of the NR2B-NMDAR selective antagonists, Ro25-6981 or ifenprodil, directly into the CA1 region, impair spatial working memory in DAT task with 30-s delay (not 5-s delay), but severely impair error-correction capability in both 5-s and 30-s delay task. Furthermore, intra-CA1 inhibition of NR2B-NMDARs impairs spatial working memory in DMP task with 10-min delay (not 30-s delay). Our results suggest that hippocampal NR2B-NMDARs are required for spatial working memory in long-delay task, whereas spare for spatial working memory in short-delay task. We conclude that the requirement of NR2B-NMDARs for spatial working memory is delay-dependent in the CA1 region.