Impaired contextual fear extinction in GCV-treated Nestin-tk transgenic mice. A, Experimental scheme for B–D. B, Contextual fear conditioning (CFC) is similar in tg-GCV and wt-GCV mice, as indicated by pre-CFC (t(25) = 0.751, p > 0.46; for tg-GCV, n = 14, for wt-GCV, n = 13) and CFC (t(25) = 0.0485, p > 0.96) freezings. C, tg-GCV mice were impaired in the extinction of conditioned contextual fear response as compared to wt-GCV mice when extinction training occurred 24 h after conditioning (ANOVA, F(1,25) = 4.429, p < 0.046). D, tg-GCV mice demonstrated significantly higher levels of freezing in training context A (ctx A) than wt-GCV mice (t(25) = 2.74, p < 0.011). In a considerably different context B (ctx B), tg-GCV and wt-GCV mice showed similar levels of freezing (t(25) = 0.109, p > 0.91). E, Experimental scheme for F–H. F, CFC is similar in tg-GCV and wt-GCV mice, as indicated by pre-CFC (t(18) = 1.09, p > 0.28; n = 10 for each group) and CFC (t(18) = 0.120, p > 0.90) freezings. G, tg-GCV mice displayed extinction behavior similar to that of wt-GCV mice when extinction training occurred 4 weeks after conditioning (ANOVA, F(1,18) = 0.9315, p > 0.34). H, tg-GCV mice demonstrated similar levels of freezing in both ctx A (t(18) = 0.229, p > 0.82) and ctx B (t(18) = 1.50, p > 0.15). I, Experimental scheme for J–L. J, CFC is similar in tg-GCV and wt-GCV mice, as indicated by pre-CFC (t(18) = 0.163, p > 0.87; for tg-GCV, n = 9, for wt-GCV, n = 11) and CFC (t(18) = 0.467, p > 0.64) freezings. K, tg-GCV mice displayed extinction behavior similar to that of wt-GCV mice (ANOVA, F(1,18) = 7.359 × 10−5, p > 0.99). L, tg-GCV mice demonstrated similar levels of freezing in both ctx A (t(18) = 1.42, p > 0.17) and ctx B (t(18) = 0.0761, p > 0.94). #Data for ctx A in D, H, and L are the same data for the last time point (test) in C, G, and K, respectively. ext, Extinction trial. *p < 0.05. Error bars represent ± SEM.