Egocentric working memory impairment and dendritic spine plastic changes in prefrontal neurons after NMDA receptor blockade in rats.

Working memory may involve context-dependent allocentric or own movement-dependent egocentric strategies. While allocentric working memory can be disrupted by N-methyl-D-aspartate (NMDA) blockage, the possible effects of NMDA receptor manipulation on the egocentric strategy have not been studied. Because dendritic spine plasticity in part underlies working memory-related behavioral efficiency, egocentric working memory performance was evaluated in adult rats following NMDA receptor blockade with 10mg/kg of the NMDA-receptor antagonist CPP, i.p. Dendritic spine density and the proportion of different spine types (thin, stubby, mushroom, wide, branched and double) were assessed in third-layer pyramidal neurons of the dorsomedial prefrontal cortex, after behavioral testing. Working memory was evaluated by challenging the rats to resolve twelve trials per day in a single-day session over five consecutive days, in a "cross-arm" maze and according to a delayed match-to-sample procedure. In control animals, the dendritic spine density remained unchanged after behavioral testing, although the proportion of mushroom spines decreased while that of the branched spines increased. NMDA receptor blockade impaired the behavioral performance of rats and resulted in a decrease in dendritic spine density when compared to the control animals, and dendritic spine types were unchanged. These results suggest that behavioral efficiency of egocentric working memory is dependent on NMDA receptor activation, and that plastic changes in spine cytoarchitecture may play a key role in behavioral performance.