Figure 3.

Enhanced long-term memory in gadd45b^−/− mice. A, Mice were trained with mild, moderate and robust cue-plus-context fear conditioning paradigms and returned to the training chamber in the absence of a footshock after 24 h. Knock-outs exhibited significantly higher percentage freezing (p < 0.05) after mild and moderate but not robust training. B, Mice trained with the moderate paradigm were tested for contextual memory at 1 h. No significant effects of genotype were found during training (left) or testing (right). C, Mice trained with the robust paradigm underwent extinction training for 15 d. Both genotypes exhibited significant fear extinction (p < 0.05). No main effect of genotype was found (p > 0.05). D, Mice trained with a modified mild paradigm with 0.5 mA shock were tested for contextual memory at 28 d. Mutants showed significantly (p < 0.05) higher freezing. E, Backcrossed mice were trained with modified mild paradigm (0.5 or 0.3 mA shock) and tested after 1 or 24 h. Mutants exhibited normal short-term memory and significant (p < 0.05) enhancement in long-term memory only after 0.3 mA shock training. F, Hybrid-background mice were trained with the mild paradigm and tested 1 or 24 h later in a novel context for tone-shock association. No effect of genotype (p > 0.05) was found. G, Morris water maze. Hybrid-background knock-outs exhibited significant (p < 0.05) deficits in the cued visible platform task and similar (p > 0.05) performance to wild-types during hidden platform training. Probe trials, denoted by arrows, were given at the beginning of days 5 and 8. Mutants also demonstrated augmented performance in the first but not second probe trial (right, p < 0.05). H, Backcrossed mutants trained similarly showed enhanced performance to wild-types on the first but not second probe trial (p < 0.05) (n = 6–15/group).