VNS enhancement of extinction depends on LC activation. (A) Behavioral timeline for AFC, conditioned fear response testing, and extinction training. (B) Stimulation parameters for extinction training of VNS groups. (C) Pre-Ext freezing (%) is shown with males as circles and females as triangles. Post-Ext and Remote Testing are reported as a change in percent freezing compared to Pre-Ext freezing +/− SEM (Pre-Ext normalized to 0%). Solid bars represent animals with eYFP control virus in the LC, while empty bars are rats expressing the ArchT inhibitory virus. Only VNS-treated animals infused with control virus showed a significant reduction in freezing 24 h after extinction training. Sham animals and VNS-treated animals expressing the inhibitory opsin in the LC did not show a significant reduction in freezing. These effects were observed again 14 days later during Remote Testing. Data were analyzed using a priori contrasts. (*) P < 0.05, (**) P < 0.001, (***) P < 0.0001.