Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.

与焦虑相关的疾病对认知行为疗法有反应，该疗法涉及内侧前额叶皮层（mPFC）。先前的研究表明，mPFC 的各个亚区域在调节先天焦虑方面具有不同甚至相反的作用。然而，它们在调节先天焦虑和压力引起的焦虑方面的下降预测的具体因果目标尚未完全阐明。在这里，我们发现，在前边缘皮层（PL）的各种下游通路中，mPFC的一个子区域、PL-丘脑内侧核（MD）投影和PL-腹侧被盖区（VTA）投影对焦虑表现出拮抗作用。类似的行为，而 PL-MD 投影而不是 PL-VTA 投影对于动物指导焦虑相关行为是必要的。此外，MD 投射的 PL 神经元双向调节远程而非最近的恐惧记忆检索。值得注意的是，束缚应激诱发高度焦虑状态，同时加强对 MD 投射 PL 神经元的兴奋性输入，而抑制 PL-MD 通路可挽救应激诱发的焦虑。我们的研究结果表明，PL-MD 通路的活性可能是维持一定程度焦虑的重要因素，而压力会增加该通路的兴奋性，导致不适当的情绪表达，并表明针对特定 PL 通路可能有助于焦虑的发展。用于治疗压力相关疾病的疗法。