Figure 7. Enrichment of aged mice improves hippocampus-dependent reference memory via MSK1. No differences were observed across groups in the visual cue version of the test (Genotype: F(1,51) = 0.001, p = 0.970; Housing: F(1,51) = 0.37, p = 0.570; Genotype x Housing F(1,51) = 2.26, p = 0.140; data not shown) suggesting comparable levels of visual acuity, swimming ability and motivation to navigate to the platform. (A) In the Aged groups the enriched WT mice were the best performers and did not show the age-related impairment seen in standard-housed WT mice. The RM-ANOVA analysis on the distance travelled to reach the escape platform showed a significant effect of Session F(3,153) = 12.63, p < 0.0001. Importantly the standard-housed WT mice did not show any significant learning improvement in this period F(3,42) = 1.95, p = 0.136. The analysis also showed a main effect of the Housing (F(1,51) = 15.23 p = 0.0003) where enriched mice performed better than standard-housed mice, and of Genotype (F(1,51) = 6.00 p = 0.018) where WT mice performed better than MSK1 KD mice. Although there was no significant interaction, on training day 3 and 4 the WT enriched mice clearly outperformed all the other groups. Data are presented as mean ± SEM. (B) On the probe trial the enriched WT mice had the best performance. The ANOVA showed a significant effect of Housing (F(1,51) = 8.84, p = 0.004), indicating a better performance of enriched mice, but the significant Genotype x Housing interaction (F(1,51) = 4.98, p = 0.030) and the Simple Main effects analysis showed that the difference between standard-housed mice and enriched mice was only significant in the WT mice (F(1,51) = 13.26, p = 0.001). Heatmaps below the graphs depict the arena occupancy for the mice of each group during the last day of training and the Probe trial. Individual data points are presented for each animal, with the bar graph representing the mean ± SEM of the data. Abbreviation: ns: not significant.