焦虑症是临床常见的精神障碍性疾病，部分患者使用临床常用药物治疗效果不佳且易发生药物耐受。焦虑症发病机制复杂，因此一直是临床研究热点。胆汁酸是胆汁的重要成分，在外周调控糖脂及能量代谢，其受体TGR5在中枢杏仁核、前额叶皮层和下丘脑中均有表达，参与炎症及可塑性调节。我们前期研究发现，束缚应激可以显著增加杏仁核TGR5表达，免疫荧光染色发现其主要表达于星形胶质细胞；正常动物杏仁核内注射shRNA腺相关病毒降低TGR5表达可诱发焦虑样行为。据此，本项目提出胆汁酸TGR5受体调节功能异常可能参与焦虑行为的发生发展，束缚应激引起的TGR5升高可能是一种代偿性行为。本项目利用电生理、基因修饰及行为学方法，探讨杏仁核TGR5调节星形胶质细胞功能，参与焦虑症的病理发生过程的分子机制，为焦虑症发掘治疗新策略与药物新靶点提供理论依据。

Anxiety disorder is a common psychiatric disorder in clinic. Some patients often receive poor therapeutic effect with drugs and are prone to drug tolerance. The pathogenesis of anxiety disorder is complex, so it is a hot topic in clinical research. Bile acid is an important component of bile, and it regulates glycolipid and energy metabolism in periphery. Bile acid receptor TGR5 is expressed in the amygdala, prefrontal cortex, and hypothalamus, and is involved in inflammation and plasticity regulation in the central nervous system. Our previous studies found that restraint stress could significantly increase the expression of TGR5 in the amygdala, and immunofluorescence staining showed that it was mainly expressed in astrocytes. Injection of shRNA adeno-associated virus into the amygdala of normal animals could induce anxiety-like behavior. The results suggest that abnormal function of bile acid TGR5 receptor may be involved in the pathogenesis and development of anxiety behavior, and the increase of TGR5 induced by restraint stress may be a compensatory effect. Using electrophysiological, gene modification, and holistic animal research methods, this project aims to explore the molecular mechanisms of amygdala TGR5 regulating astrocyte function and participating in the pathological process of anxiety disorder. It is helpful to provide theoretical basis for revealing the pathogenesis of anxiety disorders and discovering new therapeutic strategies and new drug targets for anxiety.