Fig. 3.

Adult Wnt5a mutant mice show a progressive decline in hippocampus-mediated behaviors. (A and B) WT mice show a significant preference for exploring a new object in the novel-object recognition task, whereas Wnt5a KO mice spent similar amounts of time with familiar and new objects. Deficits in recognition memory were evident in both 3- and 6-mo-old mutants. Dashed line indicates equal amount of time spent exploring new and familiar objects. Results are mean ± SEM from n = 21 WT mice and n = 19 KO mice at 3 mo, and n = 16 WT mice and n = 23 KO mice at 6 mo. *P < 0.05, **P < 0.01 significantly different from 50% time spent with the novel-object, two-tailed t test. (C) Timeline for the Morris water maze (MWM) tasks. (D) Three-month-old KO mice show impaired spatial learning in the Morris water maze test. Results are mean ± SEM from n = 20 WT and n = 19 KO mice. *P < 0.05, **P < 0.01, two-way ANOVA with Fisher’s least-significant difference (LSD) post hoc test. (E) Six-month-old KO mice exhibit more severe deficits in learning and fail to acquire the latency of control animals even on day 12. Results are mean ± SEM from n = 18 WT and n = 20 KO mice. *P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA with Fisher’s LSD post hoc test. (F and G) During probe trials, 3- and 6-mo-old KO mice showed less preference for the target quadrant compared with WT mice. Results are mean ± SEM, *P < 0.05, **P < 0.01, two-tailed t test. (H and I) During the memory retention test, both 3- and 6-mo-old KO mice spent less time in the target quadrant compared with control littermates. However, older mutant mice exhibited a marked decay in memory retrieval by the fifth day of the probe trial. White dashed line indicates 25% of time that mice spent in the target quadrant. Results are mean ± SEM; *P < 0.05, **P < 0.01, ***P < 0.001 significantly different from control littermates; ^#P < 0.05 significantly different from 25% line, two-tailed t test.