(A) Animals underwent 1P or 10P fear conditioning training, were sacrificed 90 min later and slices were collected to verify c-fos expression. Training resulted in greater LC c-fos expression in the 10P group than in the 1P group (N = 3 per group). (B) Animals were infused in the LC with pAAV-hM4Di-mCHerry or the control pAAV-tdTomato. Terminal projections in the BLA were silenced with local infusion of the DREADD agonist C21 (2 μg/μL, 0.5 uL/side). (C) Top: after 3 months from the viral injections, it was observed robust somatic expression in locus coeruleus neurons (right) and terminal expression in the BLA (left). Bottom: Light red represents the maximal, and dark red the minimum viral expression spread observed in the LC included in the analysis. (D) After 3 months from viral infusions, animals were infused in the BLA with C21 to block LC-BLA projections and were and trained in the 10P training protocol 5 min later. One day after training a reconsolidation-blockade procedure was conducted with intra-BLA post-reactivation anisomycin. The next day a retention test was conducted. Left: representation of infusion sites in the BLA. Right: the reconsolidation blockade procedure was effective in disrupting fear memory only in animals infused with the hM4Di virus (N = 7/9 per group). Graphs show the mean ± s.e.m. Individual values are represented with circles. *p<0.05. The full statistics are available in the Supplementary file 4 and individual values in Figure 5—source data 1.