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 (NR2BNMDARs) in spatial working memory, it remains unclear whether or not the requirement of hippocampal NR2BNMDARs 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 NR2BNMDAR 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. [ABSTRACT FROM AUTHOR]