青少期应激抑郁下前额叶皮质兴奋/抑制性失衡介导中缝背核环路谷氨酸投射机制及调肝治法干预作用研究

神经元兴奋性/抑制性（E/I）平衡是维持大脑中枢稳态与信号传输的重要基础。新近研究表明，前额叶皮质作为调控情绪认知功能的关键脑区，其E/I平衡可能在青少期抑郁发病中扮演重要角色，并通过谷氨酸受体投射至中缝背核形成环路连接。基于调肝解郁治法的临床确切疗效，课题组探索其中枢机制已初步证实调肝解郁方四逆散具有防治青少期抑郁的作用，且最新发现四逆散能改善前额叶皮质E/I平衡。立足E/I失衡的关键脑区与环路投射，探求E/I平衡对抑郁样行为的中枢调控，成为揭示调肝解郁治法治疗青少期抑郁中枢机制的关键。本研究采用在体电生理、光遗传学、钙成像等先进技术，对前额叶皮质E/I平衡、前额叶皮质-中缝背核环路进行动态监测，深入研究四逆散调节E/I平衡防治青少期抑郁行为的作用及电生理机制；并进一步针对下游中缝背核谷氨酸受体进行环路操纵，初步揭示四逆散调肝解郁治法调控神经电生理信号对抑郁行为编码的神经环路机制。

The excitatory/inhibitory (E/I) balance of neurons is an important basis for maintaining the homeostasis and signal transmission in central nervous system (CNS). Recent studies have shown that prefrontal cortex is a key brain region that regulates emotional and cognitive functions, and its E/I balance may play an important role in adolescent depression, and projects to dorsal raphe nucleus through glutamate receptors. Based on the exact clinical effect of regulating liver qi and regulating emotions, our research group has confirmed that Sinisan, a classic prescription for regulating stagnated liver qi for relieving qi stagnation, can prevent and treat depression in adolescence. The latest experiment found that Sinisan can enhance E/I ratio in prefrontal cortex. Based on E/I imbalance brain region and circuit projections, exploring the E/I balance on depression-like behaviors is the key to study the CNS mechanism of Sinisan regulating liver therapy in adolescent depression. To further study electrophysiological mechanism of Sinisan regulates E/I balance and prevent adolescent depression, we use in vivo single unit recoding, optogenetics, calcium imaging and other advanced technologies to dynamically monitor prefrontal cortex E/I balance and prefrontal cortex - dorsal raphe nucleus circuit. We further manipulate the glutamate receptor projection in dorsal raphe nucleus to initially reveal the neural circuit mechanism of Sinisan's regulating stagnated liver qi for relieving qi stagnation therapy in regulating neuroelectrophysiological signals to encode depressive behaviors.