Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.

中文翻译：

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内源性大麻素信号崩溃介导压力诱导的杏仁核-皮质增强。

杏仁核和背侧前额叶皮层（dmPFC）之间的功能耦合已牵涉到负面的情感状态的生成；然而，应激增加杏仁核-dmPFC突触强度并产生焦虑样行为的机制尚不清楚。在这里，我们显示，小鼠基底外侧杏仁核（BLA）-前缘前额叶皮层（plPFC）电路是由压力和此通路在血管生成中的激活所参与的。此外，我们证明了急性应力暴露会在相互的BLA-plPFC-BLA子电路中导致突触强度的持久增加。重要的，我们确定2-花生四烯酸甘油酯（2-AG）介导的内源性大麻素信号传导是限制谷氨酸在BLA-plPFC突触中释放的关键机制，而多峰2-AG信号传导的功能崩溃是导致持久性电路特异性突触增强和焦虑的分子机制。压力暴露后的类似行为。这些数据表明2-AG信号传导中的特定于电路的损伤可以促进BLA和pIPFC之间的功能偶联以及环境压力向情感病理学的转化。