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 10. The enrichment-induced facilitation of LTP in stratum radiatum of area CA1 is dependent upon the kinase activity of MSK1. Dual pathway fEPSP recordings from stratum radiatum in area CA1 of WT and MSK1 KD mouse hippocampal slices. Filled symbols represent the pathway to which theta-burst stimulation (TBS) was delivered at time zero and denoted by the filled black triangle. Open symbols reflect synaptic transmission in the control, non-TBS, pathway, which served as a control for the viability of the slice over the recording period. Inset fEPSPs show baseline fEPSPs (broken lines) and fEPSPs 150 min after TBS (solid lines) from representative experiments. fEPSPs were stimulus-matched for amplitude prior to TBS delivery, and normalised with respect to average fEPSP slope measurements over the 30 min prior to TBS. (A) In the Adult groups the LTP analysis was calculated for the area under the curve (AUC) in the late phase (last 60 minutes) and showed a main effect of Genotype (F(1,20) = 6.20, p = 0.022). While there was no Genotype x Housing interaction (F(1,20) = 3.44, p = 0.078), a direct comparison between WTEE and KDEE showed a pronounced significant difference F(1,20) = 9.44, p = 0.006 while the same comparison between standard-housed mice was not significant (F(1,20) = 0.22, p = 0.660). In addition, while the difference between WT SH vs. WT EE was significant (F(1,20) = 7.05, p = 0.015), the same comparison between the MSK1 mutant mice did not reach significance (F(1,20) = 0.001, p = 0.970). (B) Similarly in the Aged groups the LTP analysis was calculated for the AUC in the late phase (last 60 minutes) and showed an even stronger effect of Genotype (F(1,20) = 13.51, p = 0.001) where WT mice had greater LTP, and statistical significance for Housing (F(1,20) = 4.34, p = 0.050). A direct comparison between WTEE and KDEE showed again a pronounced significant difference (F(1,20) = 9.22, p = 0.007). The lack of late LTP in the aged standard-housed MSK1 KD mice contrasted with the appreciable LTP seen in similarly housed WT mice, and was not improved by enrichment (F(1,20) = 1.07, p = 0.312). Data are presented as mean ± SEM.