Figure 4

Effect of the D664A mutation on behavior in PDAPP mice. (a and b) Morris water maze. (a) Learning curves. Mean latencies on 6 consecutive days of training (average of 4–6 trials per day ± SEM). Repeated-measures ANOVA revealed that all groups learned the cued task [F(11, 330) = 21.56, P < 0.0001, visible]. PDAPP(J20) animals (n = 8) showed deficits during acquisition in the hidden, hippocampal-dependent component of the task. ∗, significant difference from nontransgenic PDAPP(J20) (n = 6), nontransgenic PDAPP(D664A)(B21) (n = 10), and transgenic PDAPP(D664A)(B21) animals (n = 10) [F (3, 180) = 7.16; P < 0.0001, two-way ANOVA]. (b) Day 9 probe trial. Percentage of time spent in the target quadrant during the probe trial (corrected for thigmotaxis). ∗, significant difference from nontransgenic PDAPP(J20); P < 0.05. No significant difference in the time spent in the target quadrant was observed between PDAPP(D664A)(B21) transgenic and nontransgenic animals. (c) Day 9 probe trial. Number of target crossings during the posttraining probe trial. ∗, significant difference from nontransgenic PDAPP(J20); P < 0.02 by student's t test; means ± SEM are shown. (d) Spontaneous alternation in the Y maze. Spontaneous alternation was significantly reduced in PDAPP(J20) transgenics (P < 0.05; Tukey's post hoc test applied to a significant effect of genotype in ANOVA; n = 38). The dotted line shows chance levels of performance. (e) Spontaneous activity in the Y maze. B254 transgenic animals demonstrated an increase in spontaneous activity. (f) Novel object exploration. Transgenic PDAPP(J20) animals spent significantly less time exploring a novel object (nonrelated pup) in an 8-min period (Tukey's post hoc test applied to a significant effect of genotype in ANOVA; P < 0.01) than all other groups (n = 38).