Effect of butyrolactone I on context- and tone-dependent fear conditioning. A, Experimental design of pretraining injections. B, Effect of butyrolactone I injected intracerebroventricularly (i.c.v.), into the intermediate septum (i.s.), or into the mediodorsal hippocampus (i.h.) before training on freezing during the context-dependent memory test. Statistically significant differences were observed after injections given intracerebroventricularly (t_(1,23) = 2.538), into the intermediate septum (t_(1,12) = 3.888), and into the mediodorsal hippocampus (t_(1,15) = 3.403). Group comparisons: ^ap < 0.05 versus vehicle administered intracerebroventricularly;^bp < 0.01 versus vehicle administered to the intermediate septum; ^cp < 0.001 versus vehicle administered to the mediodorsal hippocampus. Autoradiograms above the bars obtained from mice injected into the intermediate septum or mediodorsal hippocampus indicate decreased phosphorylation of histone H1 (HH1) within the septum and hippocampus of mice injected with butyrolactone I in these areas. C, Effect of butyrolactone I injected into the intermediate septum (i.s.) before training on freezing in a novel context and during the tone- dependent memory test. The treatment did not affect freezing in a novel context (t_(1,31) = 1.003; p = 0.337) or the tone (t_(1,31) = 0.529; p= 0.4809). D, Effect of butyrolactone I injected into the mediodorsal hippocampus (i.h.) before training on freezing in a novel context and during the tone-dependent memory test. The treatment did not affect freezing in a novel context (t_(1,23) = 0.553; p= 0.4645) or the tone (t_(1,23) = 1.74;p = 0.2001). E, Experimental design of post-training injections. F, Effect of butyrolactone I injected into the intermediate septum (i.s.) immediately or 3 hr after the training on freezing during the context-dependent memory test. Butyrolactone I injected into the intermediate septum impaired fear conditioning (t_(1,11) = 3.182) when applied immediately but not 3 hr after the training (t_(1,12) = 0.027). Group comparisons:^ap < 0.01 versus vehicle administered into the intermediate septum. G, Effect of butyrolactone I injected into the mediodorsal hippocampus (i.h.) immediately or 3 hr after the training on freezing during the context-dependent memory test. Butyrolactone I injected into the mediodorsal hippocampus impaired fear conditioning (t_(1,14) = 5.958) when applied immediately but not 3 hr after the training (t_(1,14) = 0.033). Group comparisons:^ap < 0.01 versus vehicle administered into the intermediate septum.