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 9. Experience-, age- and MSK1-dependent effects on CA1 stratum radiatum dendritic spine density. (A) In the Adult groups, when average CA1 stratum radiatum spine densities per animal are compared, there was a trend for enriched animals having greater spine density than standard-housed mice. (B) Representative Golgi images of secondary dendrites in stratum radiatum from CA1 pyramidal neurons across the four groups. Scale bars measure 10 μm. (C) Cumulative distribution of all spine density measurements across all groups showing rightward shifts of spine density in enriched groups. (D) In the Aged groups, when average CA1 stratum radiatum spine densities per animal are compared, there was a tendency for WT mice, but not MSK1 KD mice to show increased spine density after enrichment. (E) Representative Golgi images of secondary dendrites in stratum radiatum from CA1 pyramidal neurons across the four groups. Scale bars measure 10 μm. (F) Cumulative distribution of all CA1 stratum radiatum spine density measurements across all groups showing rightward shifts of spine density in enriched WT and standard-housed MSK1 KD mice. (G) Data from the Young groups are from Privitera et al., (2020) [36]. An across age group Univariate analysis with Genotype (WT or MSK1 KD), Treatment (SH or EE) and Age (Young, Adult and Aged) as independent variables revealed a main effect of Genotype (F(1,44) = 8.18, p: 0.006). A simple main Effects Analysis (Sidak correction) revealed a significant difference between standard-housed WT and MSK1 KD in the Young and Aged groups (F(1,44) = 4.96, p: 0.031 (G) and F(1,44) = 4.68, p: 0.036 (D), respectively confirming a previous report [34]. (H) A summary of CA1 stratum radiatum spine density changes across age, genotype and housing condition on a per animal basis (mean data from A, D, G). Enrichment consistently enhances spine density in WT mice. MSK1 KD mice typically have greater spine density, but the pattern over time, and the effects of enrichment are not correlated. In A, D, G, individual data points represent mean spine density values from individual animals (n = 4 (A, G) or 6 (D) mice), the horizontal line is the mean, and the box reflects ± 1 SD of the mean. In H data are presented as mean ± SEM. Additional CA1 stratum radiatum spine density data (per group and per animal) can be found in Supplementary Figure 3.