Fig. 2: Mirdametinib high dose (25 mg/kg) and positive control SL327 (50 mg/kg), when given with prediction error at the time of memory reactivation, blocked the reconsolidation of fear memory and reduced pERK activity in LA.

A Schematic representation of experimental protocol used. B Mean percentage of freezing in C57BL/6 mice with vehicle (n = 6), mirdametinib (25 mg/kg, n = 6), SL327 (50 mg/kg, n = 6) in experiment 3. Two-way repeated measures ANOVA. * p < 0.05, ** p < 0.01 vs vehicle. Data Mean ± SE. C Quantitative topographical analysis revealed a reduced number of pERK positive neurons in LA in mirdametinib and SL327 groups compared to vehicle control. D Bin matrix used for dividing the LA superimposed on pERK immunolabeled brain section. E Microanatomical neuron density map depicting the mean spatial distribution of activated neurons in the LA from all study groups at −1.82 Bregma. G Below each map is its coefficient of variance (CV) map, generated by dividing the standard deviation by the mean. F A visual representation of the q value matrix. q < 0.1 were depicted in color for visualization purposes. Multiple comparisons (one-way ANOVA) revealed that 10 out of 63 were statistically different (q < 0.1) between experimental conditions. Subsequently planned comparisons demonstrated that mirdametinib and SL327 reduced a comparable number of neurons (red bins) that were lower than vehicle group in 8/10 bins. In bin 61, mirdametinib was associated with lower neurons (blue bins) than vehicle and SL327 control. Bin 18 was unique to SL327, with a smaller number of pERK positive neurons (yellow bins) in comparison to vehicle and mirdametinib groups. H Representative pictures of each group. IHC Immunohistochemistry.