果蝇获得性无助行为的神经回路及其相关神经递质研究

Recent years, depression becomes one of the most common mental disorders in the world. Therefore, more and more researches are invested in this area. Learned helplessness phenomenon was found in 1960s using dogs as animal model and since then considered as an important research model for human depression..Many studies have revealed that uncontrollable pressures could lead to learned helplessness in kinds of animals, such as dogs, rats, mice, gold fishes. In our previous study, we established a brand new research model using Drosophila for learned helplessness phenomenon. The helpless flies showed reduced activity and slower escape behavior in compare with control group. .In this project, a new setup of experimental apparatus will be first completed; Imaging technique will be utilized to obtain the brain areas and neuron clusters which involved in this behavior; next step is using Gal4-UAS system to manipulate neuron transmitter system, aimed to find the functions of neuron transmitters on learned helplessness in flies. .The accomplishment of this project will provide insight into understanding learned helplessness phenomenon and also into exploration of pathogenesis of human depression.

获得性无助行为是对类抑郁症疾病研究的一种有效的研究范式。在许多动物中，不可控制的刺激可以导致获得性无助行为。我们此前的研究利用果蝇建立了获得性无助行为的研究模型，发现“无助果蝇”在活跃度，以及逃离刺激次数和时间方面与对照组有显著差别。.在本项目中，将首先在原平台基础上建立新的实验平台，并从软硬件两方面完善该平台；然后通过成像技术，对影响果蝇获得性无助行为的脑区和神经元从广泛到局限地进行定位；再利用果蝇丰富且成熟的转基因技术，在定位的脑区和神经元中改变果蝇神经递质和多肽分子的表达水平，确定其对果蝇获得性无助行为的影响；并探讨获得性无助行为的发生机制。本项目的完成，将加深对获得性无助行为的理解，并为探索类抑郁症的发病机制提供重要参考。

习得性无助行为是针对人类抑郁症研究的一种有效的、广泛使用的研究范式。在此类研究中，模式生物经过不可控制惩罚性刺激之后，均可表现出习得性无助行为。我们此前的研究利用果蝇建立了习得性无助行为的研究模型，发现“无助果蝇”在活跃度，以及逃离刺激次数和时间方面与对照组均有显著差别。在前期搭建试验平台的基础上，本课题对果蝇的习得性无助行为进行了更加深入到研究。研究发现，“被动果蝇”的习得性无助行为并不一定需要“主动果蝇”来诱导；仅仅利用随机刺激亦可使果蝇表现出相应的习得性无助行为。此外，多种抗抑郁类药物对果蝇的习得性无助行为有减弱作用。通过筛选神经递质突变品系，发现章胺，五羟色胺和多巴胺对果蝇习得性无助行为具有重要影响；而后利用RNAi阻断不同脑区章胺表达发现，中央复合体在此过程中起重要作用。