杏仁核在慢性应激加重神经病理痛中的作用及局部微环路机制，我们实验室前期已经有多篇相关的研究报道。在此基础上，本项目拟通过以下研究阐明前边缘皮层(PL)-基底外侧杏仁核(BLA)环路在慢性应激加重神经病理痛中的作用及机制：1）确定PL脑区锥体神经元结构和功能的损害、以及由此引起的BLA脑区输出神经元的功能活动增强，在慢性应激加重神经病理痛中的作用。2）确定在慢性应激或神经病理痛状态下，由PL驱动的对BLA输出神经元的前馈抑制降低，是导致杏仁核输出增强的重要原因；这种前馈抑制由SOM阳性GABA能神经元所介导。3）确定在慢性应激或神经病理痛状态下，由BLA驱动的对PL输出神经元的前馈抑制增强，增强的前馈抑制促进PL输出神经元的功能活动进一步降低；PV阳性GABA能神经元介导这种前馈抑制。综上以期证明：PL和BLA输出神经元之间相互驱动的前馈抑制调节，在慢性应激加重神经病理痛中的作用及分子机制。

The role and the local microcircuit mechanism for the amygdala in chronic stress-induced exacerbation of neuropathic pain have been examined detailedly in our previous studies. In this research project, we will further investigate the role and the mechanisms for the prelimbic cortex (PL)-basolateral amygdala (BLA) circuit in chronic stress-induced exacerbation of neuropathic pain. First, to determine whether the damage of PL projection neurons structure and functional activity and the resulting enhancement of BLA projection neurons functional activity are involved in chronic stress-induced exacerbation of neuropathic pain. Second, to determine that in the state of chronic stress or neuropathic pain, whether the loss of the feedforward inhibition to BLA projection neurons driven by PL will result in the enhancement of amygdala output, and that this PL-driven feedforward inhibition is mediated by somatostatin (SOM)-positive GABAergic interneuron. Last, to determine that in the state of chronic stress or neuropathic pain, whether the feedforward inhibition to PL projection neurons driven by BLA is increased; also, to examine whether this BLA-driven feedforward inhibition is mediated by parvalbumin (PV)-positive GABAergic interneuron. Moreover, we also explored whether the enhanced feedforward inhibition driven by BLA will further impair the functional activity of PL projection neurons. This study will clarify the role and molecular mechanism for the mutual driven feedforward inhibition between PL and BLA projection neurons in chronic stress-induced exacerbation of neuropathic pain.