Fig. 2: Valence matters: Artificial reactivation of a neutral home cage experience during reconsolidation is not sufficient to disrupt a  fear memory.

a Viral strategy and experimental design. dDG cells encoding positive, neutral, and negatively-valenced behavioral epochs were tagged off-DOX (orange). b Negative groups were initially FC in an alternate context (Context C). These mice showed greater freezing post-shock (two-way RM ANOVA: F(1,10) = 168.4, P < 0.0001). c The next day all mice were FC. While all mice showed increased freezing post-shock (three-way RM ANOVA: F(1,37) = 295, P < 0.0001), mice in the negative groups demonstrated higher freezing pre-shock (Negative: vs. Positive P < 0.0001, vs. Neutral P < 0.0001) (two way RM ANOVA: F(2,40) = 27.55, P < 0.0001), and post-shock (three-way RM ANOVA: F(2,37) = 25.25, P < 0.0001). d During recall, negative groups continued to exhibit increased freezing (three-way RM ANOVA: F(2,37) = 3.286, P < 0.0486, Valence × Virus × Time). Negative-ChR2 mice froze more than neutral-ChR2 mice in the first (P = 0.0086) and last 10 min (P < 0.0001) and more than positive-ChR2 mice at both time points (P = 0.255, P < 0.0001). Positive (P = 0.0072) and neutral (P = 0.0002) ChR2 mice showed faster decline in freezing compared to eYFP controls. e During EXT1, positive and neutral-ChR2 mice froze less than other groups (three-way ANOVA: F(2,37) = 4.107, P = 0.0245, Valence × Day; F(2,37) = 6.841, P = 0.0128, Virus × Day). f No group differences observed during IS. g During RE, positive ChR2-mice showed reduced fear compared to eYFP controls (P = 0.0249) and both negative-ChR2 (P = 0.0147) and eYFP (P = 0.0498) groups (two-way ANOVA: F(1,37) = 5.923, P = 0.0199, Virus; F(2,37) = 3.440, P = 0.0426). h Positive-ChR2 mice froze less than other groups except neutral-ChR2 mice at RE compared to IS (three-way RM ANOVA: F(1,37) = 5.912, P = 0.0200, Day × Virus). i Viral strategy and experimental design. dDG cells encoding acute cocaine-exposure (positive) were tagged off-DOX (orange) and 24 h later mice were placed in the OF (10 min) where tagged dDG cells were reactivated in the last 5 min. No group differences in locomotor j line crossings k distance traveled and l speed m or anxiety measures (percentage time spent in center). Data represented as means ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.00. dDG dorsal dentate gyrus, DOX doxycycline, EXT extinction, OF open field, IS immediate shock, RE reinstatement. Source data provided as a Source Data file.