Figure 2. Post-training reduction of adult neurogenesis prevents forgetting of water maze platform location.

(a) Nestin TK⁻ (n=12) and TK⁺ (n=12) mice were trained in the water maze and were then treated with vanganciclovir for 6 weeks. Spatial memory retention was probed, and then mice were trained on a reversed platform location. (b) Probe test performance in TK⁻ and TK⁺ mice before and after vanganciclovir treatment. Whereas TK⁻ mice searched the target zone less post-vanganciclovir (indicating forgetting of the platform location), TK⁺ searched target zone equivalently pre- versus post-vanganciclovir (indicating an absence of forgetting; Genotype × Delay interaction: F_1,22=4.07, P=0.056). (c) Discrimination of the platform zone (compared with the opposite zone) declined in vanganciclovir-treated TK⁻ but not TK⁺ mice in the 6-week retention delay (Genotype × Delay interaction: F_1,22=5.20, P<0.05). (d) Doublecortin⁺ neurons were reduced in TK⁺ mice (F_1,22=47.03, P<0.0001). (e) Examples of doublecortin⁺ neurons in the dentate gyrus of TK⁻ and TK⁺ mice. Scale bars, 50 μm. (f) Suppression of neurogenesis impaired reversal learning in TK⁺ mice (Genotype main effect: F_1,25=5.14, P<0.05). (g) TK⁺ mice spent less time in the target zone compared with TK⁻ mice (Genotype × Zone interaction: F_1,22=4.42, P<0.05). Data analysis used ANOVA (b,c,d,g) and repeated-measures ANOVA (f). *P<0.05 by Newman–Keuls post hoc tests for multiple comparisons. Data shown are mean±s.e.m.