Fig. 2

Aged DKI mouse learning and memory impairment at 9 months requires Prnp expression. A 9‐month‐old WT (blue), Prnp^−/− (red), DKI (green) and DKI; Prnp^−/− (purple) mice repeated the MWM to assess the onset of spatial memory deficit. Latency is defined as the average time of 4 trials to find a hidden platform across 6 acquisition sessions. DKI mice took significantly longer to reach the platform during the final acquisition session compared to WT, Prnp^−/− and DKI; Prnp^−/−. The DKI; Prnp^−/− mice showed learning equal to WT levels. To rule out the contribution of visual or motor impairments, latency to a visible platform was measured and no significant difference was observed in any genotype compared to WT. Data are graphed as mean ± SEM, analyzed by two‐way ANOVA with Dunnett’s multiple comparisons test, *P < 0.05, n = 18 for WT, n = 19 for Prnp^−/−, n = 19 for DKI, and n = 19 for DKI; Prnp^−/−. B 24 h after completing the final acquisition session, all 4 genotypes completed a probe trial. The percent permanence is defined as the fraction of 60 s spent in the quadrant where the platform was during acquisition trials. DKI mice spent significantly less time in the target quadrant compared to WT, Prnp^−/− and DKI; Prnp^−/− mice. The DKI; Prnp^−/− mice showed rescue equal to WT levels. Data are graphed as mean ± SEM, analyzed by ordinary one-way ANOVA with Dunnett’s multiple comparisons test, *P < 0.05, ***P < 0.001, n = 18 for WT, n = 19 for Prnp^−/−, n = 19 for DKI, and n = 19 for DKI; Prnp^−/−. C 9-month-old WT, Prnp^−/−, DKI and DKI; Prnp^−/− mice repeated the NOR test. All 4 genotypes preferred to interact with the novel object compared to the familiar object, though DKI; Prnp^−/− mice exhibited a trend towards less novel object recognition. Data are graphed as mean ± SEM, analyzed by two‐way ANOVA with Sidak's multiple comparisons test, * P < 0.05, ***P < 0.001, ****P < 0.0001, n = 12 for WT, n = 17 for Prnp^−/−, n = 16 for DKI, and n = 16 for DKI; Prnp^−/−