Data were then analyzed separately for each sex using selleck kinase inhibitor two-way ANOVAs. When appropriate, post-hoc comparisons were carried out using the Newman�CKeuls test. Nonparametric tests (exact Fisher��s test) were used to compare the percentage of mice using the spatial strategy. All values are expressed as mean �� SEM. Differences were considered statistically significant at p < .05. Results Cognitive Function in ��4+/+ and ��4?/? mice Y maze Spontaneous alternation behavior did not differ between ��4+/+ and ��4?/? mice (data not shown). Analyses of the percentage of spontaneous alternations and total number of arm entries revealed no effect of Genotype or Genotype by Sex interaction. Barnes Maze Task acquisition. Both ��4+/+ and ��4?/? mice acquired the Barnes maze task during 12 daily training trials (Supplementary Figure 1).

The ANOVA revealed that the number of errors (Supplementary Figure 1a; main effect of Trials: F(11, 913) = 21.15, p < .00001) and time to find the escape tunnel (Supplementary Figure 1B; main effect of Trials; F(11, 913) = 19.80, p < .0001) were significantly decreased across training trials. There was a significant interaction between the factors Trial and Sex for the number of errors (F(11, 913) = 3.42, p < .01) and time to find the escape tunnel (F(11, 913) = 2.77, p < .01), with females learning faster than males (data not shown). There was no significant main effect of the factors Sex or Genotype and no interaction effects. A comparison of strategies used by ��4+/+ and ��4?/? mice during task acquisition revealed no Genotype differences (Supplementary Figure 2 in Supplementary material online).

Across three 4-trial blocks, all mice progressively increased the use of spatial (main effect of Block; F(2, 166) = 34.7, p < .0001; Supplementary Figure 1C) and serial (main effect of Block; F(2, 166) = 7.3, Anacetrapib p < .001; Supplementary Figure 1B) strategies and decreased the use of the random strategy (main effect of Block; F(2, 166) = 62.17, p < .0001; Supplementary Figure 1a). By the end of task acquisition (Block 3), independent of genotype, female mice were using the random search strategy significantly less (main effect of Sex; F(3, 83) = 5.8, p < .05) and the serial strategy significantly more (Block by Sex interaction; F(2, 166) = 4.72, p < .01) compared with male mice (data not shown). Additional analyses were performed to compare the use of a spatial strategy to find the target defined as the percentage of mice using spatial memory in at least three of the four last training trials in Block 3. Male ��4?/? mice tended to use the spatial strategy less than ��4+/+ males or females of either genotype (Figure 1A). Figure 1. Use of spatial strategy to find the escape tunnel in the Barnes maze.