Figure 2

BACEi treatment does not alter spatial memory or cognitive flexibility in mice. (A) In the Morris water maze (MWM), WT and Sez6 TKO mice swam an equivalent distance to reach the hidden platform during acquisition training (from day 2) and reversal training (i) and Sez6 TKOs took a longer time than WT mice to find the hidden platform during reversal training (ii). 30 mg/kg/day BACEi treatment did not significantly affect pathlength or latency within genotypes (i–ii), or the ability of mice to successfully learn the hidden platform location in the acquisition and reversal probe trials (iii) although a tendency for BACEi treated WT mice to take longer to find the platform than vehicle treated WT mice on the first day of reversal training is noted (ii). n = 15–16 per group. (Ai) Log₁₀ of pathlength (mm) and (Aii) Log₁₀ of latency (seconds): 2-way RM ANOVA with acquisition and reversal analysed separately. (Ai) Acquisition: genotype p = 0.015, day p < 0.0001, treatment p = 0.73. (Ai) Reversal: genotype p = 0.891, day p < 0.0001, treatment p = 0.206. (Aii) Acquisition: genotype p = 0.091, day p < 0.0001, treatment p = 0.855. (Aii) Reversal: genotype p = 0.0004, day p < 0.0001, treatment p = 0.095. No significant interactions observed. Stars indicate a significant Bonferroni post-hoc at the level of genotype × day effect (treatment groups pooled). Aiii: 95% CI did not overlap with chance (7.5 s) for any group. (B) Sez6 TKO mice had enhanced fear learning at the 24 h context fear conditioning (CFC) retention test and delayed fear extinction compared to WT mice, but behaviour within each genotype was unaffected by 30 mg/kg/day BACEi treatment. n = 15–16 per group. 2-way RM ANOVA: genotype p < 0.0001, timepoint p < 0.0001, treatment p = 0.96, genotype × timepoint p < 0.0001, no other significant interactions. Stars indicate a significant Bonferroni post-hoc at the level of genotype × timepoint effect. (C) In the light/dark box test of anxiety, WT and Sez6 triple KO mice treated with 30 mg/kg/day BACEi spent an equivalent amount of time in the light zone (i) and made an equivalent number of entries into the light zone (ii). n = 15–16 per group. 2-way ANOVA. (Ci) genotype p = 0.62, treatment p = 0.16. (Cii) genotype p = 0.79, treatment p = 0.72. No significant interactions. All graphs show mean ± SEM except (Aiii) which shows mean ± 95% CI. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.