Figure 2. ICI administration disrupts working memory in NonTg mice and impairs spatial memory in 3xTg-AD mice.

(A) During novel object recognition, 3xTg-AD/NaCl mice are not able to discriminate between objects, and ICI administration has no detectable effect on mouse performance. In contrast, NonTg/NaCl mice spend ~71% of their time exploring the new object, and ICI administration disrupts this form of working memory in the NonTg mice, as they perform at chance levels. These changes were statistically significant as indicated by one-way ANOVA with a Bonferroni’s post-hoc test (p = 0.017). (B) Learning curve of mice trained in the spatial reference version of the MWM. Mice were trained to swim to a hidden platform in a tank using extramazal visual cues. Each day represents the average of four training trials. All genotypes showed significant improvements over the 5 days of training. However, the 3xTg-AD/ICI mice performed significantly worse than the other three groups at day 3 and day 4 as indicated by a greater distance traveled to find the hidden platform (*; p < 0.05 and 0.01, respectively). Additionally, 3xTg-AD/ICI mice are significantly impaired compared to both NonTg groups at day 4 and 5 (#; p < 0.05). (C–D) Probe trials, indicative of spatial memory were conducted 24 hours after the last training trail. The latency to reach the platform location during a 60-second trial was significantly higher for the 3xTg-AD/ICI mice compared to the other three groups (p = 0.01). We also found a strong trend toward an exacerbation of performance in the 3xTg-AD/ICI mice when measuring the number of platform location crosses during the duration of the trial (p = 0.09; Fig. 2D). (E) Average swim speed during the probe trials was not statistically significant among the four groups (p = 0.11). Data are presented as means ± SEM.