Fig. 2
Depletion in neurogenesis enhances impairments in contextual fear conditioning. a Schematic presentation of the experimental paradigm used. A (shock) and C (no shock) are distinct contexts. Mice were fed with either vehicle or valganciclovir chow after weaning for 1.5 months prior to the contextual fear conditioning task. b, d, f, g Based on anticipatory freezing behavior nontransgenic (N = 11) b), APPswePS1ΔE9 (N = 14) (d), vehicle-fed Nestin-δ-HSV-TK [((f), N = 12)] and valganciclovir-fed Nestin-δ-HSV-TK [(g), (N = 8)] mice are able to distinguish context A from C (repeated measures two-way ANOVA, b. Context: F1,20 = 46.64, P < 0.0001; d. Context: F1,26 = 6.36, P = 0.0182; f. Context: F1,22 = 31.40, P < 0.0001; g. Context: F1,14 = 19.72, P = 0.0006). i vehicle- treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK (N = 7) are able to distinguish between the contexts (repeated measures two-way ANOVA, i. Context: F1,12 = 7.90, P = 0.0157). j valganciclovir-treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK (N = 9) mice are unable to distinguish between the two contexts (repeated measures two-way ANOVA, j. Context: F1,16 = 2.82, P = 0.1125) .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 differences in the animal’s ability to discriminate between contexts between days; however, (h) Nestin-δ-HSV-TK mice had a significant Context x Days interaction (repeated measures two-way ANOVA, Context x Days: F2,36 = 3.56 P = 0.0388). l Valganciclovir-fed Nestin-δ-HSV-TK exhibited significantly better abilities to discriminate between contexts A and C compared to valganciclovir-fed APPswe/PS1ΔE9 and APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice (repeated measures two-way ANOVA, *Nestin-δ-HSV-TK vs. APPswe/PS1ΔE9;, #Nestin-δ-HSV-TK vs. APPswe/PS1ΔE9;Nestin-δ-HSV-TK) with the genotype having a significant influence on discrimination between contexts A and C (repeated measures two-way ANOVA, Genotype: F2,22 = 7.00 P = 0.0044). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; # P < 0.05; ## P < 0.01