Fig. 3.

Ablation of neurogenesis compromises pattern separation in APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice. a Schematic presentation of the experimental paradigm used to test pattern separation. Two very similar contexts, A (shock) and B (no shock). Nontransgenic [N = 11, (b)], APPswe/PS1ΔE9 [N = 13, (d)], vehicle- treated Nestin-δ-HSV-TK [N = 12, (f)] and valganciclovir- treated Nestin-δ-HSV-TK [N = 7, (g)] mice are able to distinguish context A from B (repeated measures two-way ANOVA, b. Context: F_1,20 = 18.20, P = 0.0004; d. Context: F_1,16 = 7.06, P = 0.0172; f. Context: F_1,22 = 13.24, P = 0.0014; g. Context: F_1,12 = 22.87, P = 0.0004). i vehicle-treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice (N = 7) exhibit similar but not identical learning patterns to APPswe/PS1ΔE9 mice (repeated measures, two-way ANOVA, F_1,10 = 18.09, P = 0.0017). j Valganciclovir-treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK (N = 8) mice are unable to distinguish between the two contexts for the first three days (repeated measures, two-way ANOVA, F_1,14 = 4.45, P = 0.0534). c, e, h, k Discrimination ratios in (c) nontransgenic, (e) APPswe/PS1ΔE9, (h) Nestin-δ-HSV-TK, and (k) APPswe/PS1ΔE9;Nestin-δ-HSV-TK revealed no significant difference in the animal’s ability to discriminate between contexts between days. l There were no significant differences in discrimination ratios between days for valganciclovir-fed Nestin-δ-HSV-TK, APPswe/PS1ΔE9, and APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice but there was a significant effect overall across days (repeated measures two-way ANOVA, Days: F_5,100 = 10.50 P < 0.0001). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001