伏隔核Tac1神经元调节抑郁症神经环路的机制研究

抑郁症，是一种和神经系统功能紊乱相关的疾病。抑郁症的症状包括：情绪低落、快感消失和焦虑等。这些症状的发生提示着我们在大脑中存在着不同的神经环路对应调节着抑郁症的不同症状。对于抑郁症的研究表明，伏隔核及其参与的神经环路在抑郁症的形成过程中起着重要的作用。在本课题的前期工作中，我们发现特异性敲减伏隔核侧壳Tac1基因的表达可以导致小鼠出现抑郁样，尤其是快感消失的行为；在慢性社交击败压力之后，伏隔核侧壳的Tac1神经元的兴奋性降低；通过化学遗传学手段，我们特异性的抑制伏隔核侧壳Tac1神经元的兴奋性，可以导致小鼠出现抑郁样的行为。本课题计划通过光遗传学、化学遗传学、药理学、电生理、神经环路示踪和动物行为学等技术手段，深入研究伏隔核Tac1神经元在抑郁症发生神经环路中的调节作用，为抑郁症的理论研究提供新的基础，为抑郁症的治疗寻找新的靶点。

Major depressive disorder (MDD) is associated with neuronal deterioration in the brain. MDD presented with multiple symptoms: depressed mood, anhedonia and anxiety. This suggest that MDD may be regulated by distinct neuronal circuits in the brain. Previous study suggested that the nucleus accumbens (NAc) is a crucial to the regulation of depression. Our data indicated that knock of Tac1 in the NAc lateral shell induced depressin, especially anhedonia; Chronic social defeat stress inhibited neuronal excitability of Tac1 neurons; Inactivation of Tac1 neurons lead mice to exhibit depressive-like behaviors. In this project, we plan to use a varity of techniques, including, behavioral testing, pathc clamping, chemogenetics, neuronal circuits tracing, optogenetics and pharmacology. With these techniques, we will investigate the underlying mechanisms that NAc tac1 neurons regulate neuronal circuits in depression and to explore new avenues for therapy.