BDNF-TrkB信号参与调控焦虑样行为。预实验结果显示敲除/敲减Gαi显著抑制BDNF诱导下游信号通路传导。慢性温和应激（CMS）焦虑模型小鼠海马区Gαi表达显著下调；而海马区shRNA敲减Gαi则诱导小鼠焦虑样行为。机制方面，BDNF诱导Gαi耦联TrkB-PSD95。而PSD95结合肽CN2097易化TrkB-PSD95-Gαi耦联，并强化BDNF下游信号活化。我们提出Gαi耦联TrkB-PSD95介导BDNF信号转导，参与调控小鼠焦虑样行为。本项目中，我们将检测CMS焦虑模型小鼠海马区BDNF，TrkB，Gαi，PSD95等表达情况。解析Gαi介导TrkB-PSD95下游信号转导的机制和其在海马神经元功能中的作用。运用海马区定位注射慢病毒等方法，在体研究Gαi调控小鼠焦虑样行为的作用。最后观察注射CN2097对小鼠焦虑样行为的影响及机制。为焦虑致病分子机制解析及干预进行新的探索。

BDNF-TrkB signaling plays a pivotal role in regulating anxiogenic behaviors. Our preliminary results showed that Gαi protein silence or knockout significantly inhibited BDNF-induced downstream signaling activation. Chronic mild stress (CMS)-induced anxiety in mice caused Gαi protein downregulation in hippocampus. Meanwhile, Gαi knockdown by lentiviral shRNA in mice hippocampus induced anxiogenic behaviors. At the molecular level, Gαi protein formed a complex with TrkB-PSD95, which presumably mediated downstream signaling transduction. CN2097, a PSD95-binding peptide, promoted TrkB-PSD95-Gαi binding and significantly enhanced BDNF-induced downstream signaling activation. We propose that Gαi mediates BDNF-TrkB signaling and regulates anxiogenic behaviors in mice. In the current proposal, we will test expressions of BDNF, TrkB, Gαi, PSD95 in the hippocampus of CMS-treated mice. The research focus will be on how Gαi protein mediates TrkB-PSD95 signaling and affects hippocampal neuronal functions. In vivo experiments will also be performed to test the role of Gαi protein in regulating anxiogenic behaviors in mice. Methods including stereotactic lentivirus plasmid injection will be applied to alter Gαi protein expression/function in hippocampus. We will also examine whether CN2097 injection would affect anxiogenic behaviors in mice. The results of this study will help to further understand the underlying mechanisms of anxiety-associated behaviors. Hippocampal Gαi protein could be a novel target for treatment of anxiety or anxiety-related psychiatric disorders.