We found that Bdnf expression in the mPFC was decreased in CUS postpartum female mice, and the critical role of the mPFC in the pathophysiology of depression is well known [35]. Consequently, we hypothesized that BDNF in the mPFC modulates depression-like behaviors. We used Cre recombinase-expressing AAV vectors to selectively delete the loxP-flanked Bdnf gene. The region-specific BDNF knockdown in the mPFC was achieved by bilateral intra-mPFC injection of AAV-Cre into adult female Bdnfflox/flox mice (Fig. 4a). Three weeks later, we confirmed the injection site and transfection of AAV in the mPFC (Fig. 4b). We first evaluated the basal depression behaviors of these mPFC-specific BDNF knockout (Bdnfflox/flox;AAV-Cre) and control mice (Bdnfflox/flox;AAV-GFP) under none stress conditions (Additional file 2: Supplementary Fig. 2a), and the results showed that mice injected with AAV-Cre showed no difference in preference for the 1% sucrose solution compared with AAV-GFP injected control mice (Additional file 2: Supplementary Fig. 2b, P = 0.784). The immobility of the AAV-Cre injected mice in the FST is comparable to the AAV-GFP injected mice (Additional file 2: Supplementary Fig. 2c, P =