Thy1-hAPPLond/Swe+ mice showed a deficit in spontaneous alternation both in the T-maze (Fig. 4a; P = 0.026) and the Y-maze (Fig. 4b; P = 0.04). However, no difference was revealed between genotypes in the

number of entries made in the Y-maze (Fig. 4c; P = 0.95). Figure 4 T-maze and Y-maze. (a) T-maze: Thy1-hAPPLond/Swe+ showed significantly (P < 0.05, t-test) less spontaneous alterations than control mice. n(each genotype) = 12. (b) Y-maze: Thy1-hAPPLond/Swe+ showed significantly (P < 0.05, t-test) less ... Morris water maze During the training phase of the MWM, both Thy1-hAPPLond/Swe+ and control mice acquired the location of the hidden platform equally well, as indicated by a significant effect of training day on escape Inhibitors,research,lifescience,medical latency (Fig. 5a and

b; effect of day, F3, 63 = 44.92, P < 0.0001; genotype × day interaction, F3, 63 = 1.21, P = 0.32) and distance moved to find the hidden platform (Fig. Inhibitors,research,lifescience,medical 5c; effect of day, F3, 63 = 26.62, P < 0.0001; genotype × day interaction, F3, 63 = 0.85, P = 0.47) and a lack of Inhibitors,research,lifescience,medical a genotype × day interaction in both cases. For velocity, we did not find a genotype difference (Fig. 5d; effect of genotype, P = 0.34). During the probe trial, Thy1-hAPPLond/Swe+ mice and control littermates spent significantly more time in the target quadrant, indicating normal memory retrieval (Fig. 5e; effect of genotype, F1, 21 = 0.56, P = 0.462; effect of quadrant, F3, 63 = 19.05, P < 0.0001; genotype × quadrant interaction, F3, 63 = 0.19, P = 0.90). No genotype difference was revealed in the visible platform test Inhibitors,research,lifescience,medical (Fig. 5f; effect of genotype, F1, 21 = 1.99, P = 0.173; effect of trial, F3, 63 = 5.65, P = 0.0017; genotype × trial interaction, F3, 63 = 0.71, P = 0.55). Figure 5 Morris water maze. (a) Display of median tracks of Thy1-hAPPLond/Swe+ and control mice during trial 16. Acquisition of the hidden Inhibitors,research,lifescience,medical platform location did not differ between genotypes as shown by escape latency (b), and distance moved (c). (d) For velocity, ... DMP dry maze Since Thy1-hAPPLond/Swe+ mice did not

display a deficit in the water maze tests, we developed a new DMP task using a dry maze (modified Barnes maze) in an attempt to enhance detection of buy SB202190 deficits by eliminating the water and swimming factor (Fig. 6a). Before testing Thy1-hAPPLond/Swe+ and their control littermates, a validation experiment was conducted using C57BL/6J Adenosine mice and scopolamine to induce experimental memory impairment. Scopolamine-injected mice exhibited decreased learning as indicated by a significant trial effect for escape latency in combination with a significant treatment × trial interaction (Fig. 6b; effect of treatment, F1, 18 = 51.58, P < 0.0001; effect of trial, F15, 270 = 10.00, P < 0.0001; treatment × trial interaction, F15, 270 = 3.15, P < 0.0001). Calculation of the averages of escape latencies per trial confirmed this finding (Fig. 6c; effect of treatment, F1, 18 = 51.58, P < 0.