Research Paper Volume 15, Issue 13 pp 6031—6072

MSK1 is required for the beneficial synaptic and cognitive effects of enriched experience across the lifespan

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Figure 6. Environmental enrichment improves cognitive flexibility in adult mice via MSK1. No differences were observed across groups in the visual cue version of the test (Genotype: F(1,59) = 0.09, p = 0.760; Housing: F(1,59) = 1.17, p = 0.280; Genotype x Housing: F(1,59) = 2.57, p = 0.110; data not shown) suggesting comparable levels of visual acuity, swimming ability and motivation to navigate to the platform. (A) All four Adult groups showed learning over the first stage of training (Days (D) 1–4). The RM-ANOVA on distance swum to reach the escape platform showed a significant effect of Session F(3,177) = 52.38, p < 0.0001. It also showed a main effect of Genotype F(1,59) = 7.19 p = 0.010 where WT mice performed better than MSK1 KD mutant mice. Although there was no significant interaction of Genotype x Housing, the enriched WT mice were significantly better than standard-housed WT mice (F(1,59) = 4.09 p = 0.048) while no significant difference was seen between standard-housed or enriched MSK1 KD mice (F(1,59) = 0.32, p = 0.570). On the Reversal (R) learning stage (2 days) the RM-ANOVA on the distance swum to reach the new escape platform location showed an effect of session F(1,59) = 36.53 p < 0.0001 and Genotype F(1,59) = 16.97, p = 0.0001 indicating that all groups learned over the time but WT mice performed better than MSK1 KD mice. Although there was no significant interaction, the WT mice performed much better than the MSK1 KD mice in both standard and enriched housing (F(1,59) = 6.77, p = 0.012 and F(1,59) = 10.37, p = 0.002, respectively). Data are presented as mean ± SEM. (B) On the probe trial 24 hours later WT mice showed the best goal directed behaviour for the reversed location of the escape platform (south west quadrant) and the standard-housed MSK1 KD mutant mice showed the worst performance. The Univariate ANOVA on the total time spent in the reversal quadrant (where the platform had been last) showed a strong effect for Genotype (F(1,59) = 9.15, p = 0.004; not shown). The effect of genotype was also significant for latency to enter the Reversal platform area (F = 7.91 p = 0.007). Although the interaction did not reach significance, the Simple Main effects showed a significant difference on the time spent in the reversal platform quadrant between enriched WT mice and enriched MSK1 KD mice (F(1,59) = 9.28, p = 0.003) and between standard-housed WT and MSK1 KD mice on the latency to reach the reversal platform location (F(1,59) = 6.07, p = 0.017). Heatmaps below the graphs depict the arena occupancy for the mice of each group during the last day of reversal learning and the Probe trial. Individual data points are presented for each animal, with the bar graph representing the mean ± SEM of the data.