129S1 mice exhibit spatial learning and memory deficits and higher CORT levels in the Morris water maze.
(A) Prior to training, Visible Platform trials (Vis) revealed no differences between C57BL/6 (n = 38 [16M, 22F]) and 129S1 (n = 45 [23M, 22F]) mice (comprising Cohort 6) in the latency to swim to a marked platform (p = 0.1876). Analysis of training trials (Training Day 1–9) revealed that both C57BL/6 and 129S1 mice improved performance (decreased latency) with training (p < 0.0001), but that 129S1 mice were impaired relative to C57BL/6 mice (p < 0.0001). Arrows indicate the points at which a probe trial was given. (B) Analysis of probe trials revealed that memory for the platform location (percent time spent in the target quadrant, where the platform was previously located) improved over the course of training for both C57BL/6 and 129S1 mice (p < 0.0001), but that 129S1 mice exhibited memory deficits relative to C57BL/6 mice (p < 0.0001). Post-hoc analysis showed that 129S1 mice spent significantly less time in the target quadrant than C57BL/6 mice on Probe trials 1 and 2 (Probe 1, p = 0.0023; Probe 2, p < 0.0001) but exhibited equal performance by Probe 3 (p = 0.1035). The dashed line indicates “chance” performance level (25% time in the target quadrant). (C) 129S1 mice swam more slowly than C57BL/6 mice (average of all trials in each phase are shown; Visible Platform, p = 0.0004; Training Trials, p = 0.0123; Probe Trials, p = 0.0316). (D–E) Analysis using Gallagher's proximity measures (lower values reflect better performance) showed that, even when differences in swim speed are accounted for, both strains improved performance over the course of the experiment (Day of Training: D, p < 0.0001; Probe Number: E, p < 0.0001) but the 129S1 mice still exhibited impaired performance in both training trials (D, p = 0.0002) and probe trials (E, p < 0.0001). Further, post-hoc analysis showed that 129S1 mice exhibited significantly worse memory for the platform location compared to C57BL/6 mice on Probe trials 1 and 2 (Probe 1, p = 0.0084; Probe 2, p < 0.0001) but showed equal performance by Probe 3 (p = 0.0807). Arrows in D indicate the points at which a probe trial was given. (F) At the end of each probe trial, a pre-determined, randomized subset of animals (129S1: n = 10 [5 M, 5 F]; C57BL/6: n = 10 [5 M, 5 F] for Probe 1, Probe 2, and Probe 3) was removed from the experiment to measure CORT levels. Analysis showed that 129S1 mice exhibited higher CORT levels over the entire course of the water maze experiment compared to C57BL/6 mice (p < 0.0001). For all panels, asterisks indicate significant main effects and crosses indicate significant post-hoc tests.