The overall analysis of the experiment was done by a factorial analysis of variance (ANOVA) with genotype and age as between subject factors. Where appropriate, simple effects were http://www.selleckchem.com/products/MG132.html evaluated using one-way ANOVA. In analyses requiring multiple comparisons between means, the Bonferroni adjustment of ?? level minimizing Type I (family-wise) error rate was used [46]. A priori comparisons were performed using the Bonferroni t test (MODLSD), and post-hoc multiple pair-wise comparisons were done using the Student-Newman-Keuls (SNK) test [46]. All statistical analyses were done using the Statistical Package for Social Sciences (SPSS Inc. Chicago) version 19 for Macintosh. Comparisons between two independent groups were done using a Student t-test.

Spearman’s rank correlation was used to assess the associations between A?? burden and freezing behavior, and partial correlation was used to evaluate associations while controlling for the effect of genotype. Due to the nonparametric nature of the data obtained in the SHIRPA screen, these data were analyzed using the ??2 test [47]. The critical ?? level was set to 0.05 in all analyses. All values in the text and figures represent means ?? the standard error of the mean (SEM). Results Training: exploration and response to foot-shock There was no difference between the CRND8 and control nTg mice in the exploratory activity preceding the first CS-US presentation (data not shown). All mice spent, on average, less than 1% of the time on spontaneous pauses during the120 second exploration. Overall, older mice paused longer (F(2,73) = 4.

1, P < 0.05), mainly due to longer breaks in GSK-3 motor activity of 12-month-old CRND8 mice (F(2,73) = 5.8, P < 0.01, genotype by age interaction). Twelve-month-old CRND8 mice spent 2.6% ?? 0.9 of the time immobile, which was significantly longer than their younger counterparts (P < 0.01 and P < 0.05 for the comparisons with three- and six-month-old mice, respectively, Bonferroni t-test), but this amounted only to about three seconds of immobility during exploration. There was no difference in activity between the age cohorts of nTg mice. The immediate freezing response to foot-shock was significantly lower in CRND8 mice than in nTg littermates (F(1,73) = 29.1, P < 0.001, genotype effect, Figure ?Figure1A).1A). Also, the oldest mice of both genotypes tended to show less immediate freezing than younger mice (F(2,73) = 3.

0, P = 0.054, age effect, Figure ?Figure1A).1A). The examination of the effect of age on immediate freezing CHIR99021 GSK-3 within each genotype revealed no significant trends in the decrease of immediate freezing in nTg or CRND8 mice (F(1,41) = 2.1, NS and F(1,32) = 2.1, NS, respectively, ANOVA simple effects), confirming a weak effect of age on immediate freezing. Figure 1 Mean (?? SEM) percent of freezing by CRND8 mice and their non-transgenic (nTg) littermates at three, six, and 12 months of age.