Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory

N -methyl- d -aspartate (NMDA) receptor–dependent synaptic plasticity in the mammalian hippocampus is essential for learning and memory. Although computational models and anatomical studies have emphasized functional differences among hippocampal subregions, subregional specificity of NMDA receptor function is largely unknown. Here we present evidence that NMDA receptors in CA3 are required in a situation in which spatial representation needs to be reorganized, whereas the NMDA receptors in CA1 and/or the dentate gyrus are more involved in acquiring memory that needs to be retrieved after a delay period exceeding a short-term range. Our data, with data from CA1-specific knockout mice, suggest the possibility of heterogeneous mnemonic function of NMDA receptors in different subregions of the hippocampus.