(A) CCR5 transgenic (Tg) mice showed a memory deficit with multi-day fear conditioning. WT and CCR5 Tg mice were subjected to daily weak training (25 s baseline, followed by a 0.4 mA (1 s) shock, followed by a 5 s post-shock, and then the mice were removed from the training chamber) for 5 days. The contextual memory was measured by the freezing% during the 25 s baseline exposure. Compared to WT mice, CCR5 Tg mice showed a contextual memory deficit between day 3 and day 5 (WT n = 18, CCR5 Tg n = 17, *p<0.05, overall (genotype × training days) interaction: F(2,66) = 1.15; Main effect of genotype: F(1,66) = 4.48, Two-way ANOVA with repeated measure). (B) In the probe test given after 3 days of training in water maze, CCR5 Tg mice showed significantly higher average proximity values (i.e., searched further away from the training platform site) than WT mice (WT n = 18, CCR5 Tg n = 18, *p<0.05, Student’s t-test). In the probe test, WT mice crossed the platform zone located in the target quadrant more than in the other three quadrants; In contrast, CCR5 Tg mice did not (WT n = 18, CCR5 Tg n = 18, *p<0.05, Student’s t-test; ***p<0.001, Bonferroni posttests, Two-way ANOVA with repeated measure). (C) In the water maze task, in probe test 2 after 5 days of training, both WT mice and CCR5 Tg mice spent more time in the target quadrant than the other three quadrants. Heat maps below the bar graphs show the combined traces of the mice from each group during the probe test (WT n = 18, CCR5 Tg n = 18, ***p<0.001, Two-way ANOVA with repeated measure). Error bars indicate SEM.