Figure 1. Running-induced neurogenesis promotes forgetting of previous information and consequently facilitates reversal learning.

(a) After water maze training mice were housed conventionally (n=24) or given running wheel access (n=24) for 4 weeks before testing and reversal training. (b) Running increased the number of doublecortin⁺ neurons in the dentate gyrus (F_1,18=142.03, P<0.001). (c) Examples of doublecortin⁺ immature neurons in the dentate gyrus of sedentary versus runner mice. Scale bars, 50 μm. (d) Running reduced retention of the platform location (Group × Zone interaction: F_1,46=9.56, P<0.005), and (e) facilitated reversal learning (Group × Day interaction: F_1,46=6.31, P<0.0001). (f) TK⁺ and TK⁻ mice were trained in the water maze and were then given oral vanganciclovir treatment for 4 weeks. During this period, roughly half of the mice received running wheels and the other half remained sedentary (TK⁻ sedentary n=14, TK⁺ sedentary n=17, TK⁻ runner n=20, TK⁺ runner n=23). (g) The running-induced increases in doublecortin⁺ cells were attenuated in TK⁺ mice (Genotype × Group interaction: F_1,43=7.08, P<0.05). (h) Examples of doublecortin⁺ immature neurons in the dentate gyrus of sedentary versus runner mice TK⁻ and TK⁺ mice. Scale bars, 50 μm. (i) Post-training running induced forgetting in TK⁻ (Zone_Target>Zone_Other; P<0.05) but not in TK⁺ mice (P>0.05; Group × Zone interaction: F_3,74=5.17, P<0.005). (j) Running facilitated reversal training in TK⁻ but not TK⁺ mice (Group × Day interaction: F_12,292=1.86, P<0.05; T, target platform zone, O, average of three equivalent platform zones in other quadrants). Data analysis used ANOVA (b,d,g,i) and repeated-measures ANOVA (e,j). *P<0.05 by Newman–Keuls post hoc tests for multiple comparisons. Data shown are mean±s.e.m.