title: Delay-dependent impairment of spatial working memory with inhibition of NR2B-containing NMDA receptors in hippocampal CA1 region of rats.
abstract: 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.
authors.affiliation: Institute of Neurobiology, and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China. xuehanzhang@fudan.edu.cn
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Zhang
authors.forename: Shu-Su
authors.initials: SS
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Yi
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Li
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate