Extended Data Fig. 6: Sex stratified analysis of behavior showing improvements in associative, but not spatial learning and memory.

a-d, Percent time freezing measured during conditioning in 4s2A/FAD vs. 4s2/FAD stratified by sex. Analyses showed only one significant sex difference where 4s2/FAD males froze more than 4s2/FAD females. (n4s2A/FAD = 8 females; 8 males, n4s2/FAD = 8 females; 8 males; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; Repeated measures ANOVA with multiple comparisons; symbols denote significance by sex(es). e, Latency to platform measured in 4s2A/FAD compared to tamoxifen treated, Cre-negative 4s2/FAD controls over the 5-day hidden platform training trials (n4s2A/FAD = 10, n4s2/FAD = 10; two-tailed, paired t-test). f, Thigmotaxis (defined by 30 s of swimming around perimeter) in 4s2A/FAD and 4s2/FAD controls during hidden platform trials (n4s2A/FAD = 10, n4s2/FAD = 10; two-tailed, paired t-test). g, Latency to platform by sex showing no sex differences in 4s2A/FAD or 4s2/FAD controls. (n4s2A/FAD = 5 females; 5 males, n4s2/FAD = 5 females; 5 males; 2way ANOVA with repeated measures and multiple comparisons). h, There were no significant sex-based differences in thigmotaxis (n4s2A/FAD = 5 females; 5 males, n4s2/FAD = 5 females; 5 males 2way ANOVA with repeated measures and multiple comparisons). i-k, Number of platform crosses (i), occupancy of target quadrant (j), and occupancy of target quadrant compared to other quadrants (k) in the 72-hour memory probe. (n4s2A/FAD = 5 females; 5 males, n4s2/FAD = 5 females; 5 males; **p < 0.01, ***p < 0.001, ****p < 0.0001; two-tailed, unpaired t-test (I,k); 2way ANOVA with multiple comparisons (k)). l-n, Sex-based analyses of platform crosses (l), time in target quadrant (m), and frequency in quadrants relative to other quadrants (n) showed no sex differences (n4s2A/FAD = 5 females; 5 males, n4s2/FAD = 5 females; 5 males; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; 2way ANOVA with multiple comparisons. a-n. For detailed statistical information, see supplementary table 3. Data represent mean ± s.e.m. of biological replicates. Individual data points plotted. Sex is denoted by symbol shape: females (circle), males (triangle). Box plots show center line, median; box limits, upper and lower quartiles; whiskers, minimum and maximum.