负面情绪是在动物界中普遍存在的、原始的情绪。一般认为，长期处于负面情绪下可能导致一系列的人类神经和精神类疾病，包括抑郁症和焦虑症等。由于实验手段所限，至今我们对负面情绪的神经环路所知甚少；在认知层面，负面情绪如何影响学习记忆功能也尚未明了。我们前期的实验发现打架失败的果蝇和求偶失败的果蝇有失败行为表现；被雄性果蝇追逐求偶的雄性果蝇会有厌恶的行为表现。受这些类负面情绪影响的行为变化在时间上具有持续性，在作用模式上具有广泛性。由此，在果蝇中建立起来的类负面情绪模型将为深入研究上面两个问题提供了突破口。本申请将在前期工作的基础上，结合分子遗传学和定量行为学的方法，系统地研究在实验室条件下诱发的果蝇类负面情绪反应，并确立类负面情绪对学习记忆的影响。同时，探索负面情绪的物质基础，在基因、突触、细胞、神经环路多种水平上了解情感和记忆的相互作用，并为理解临床精神疾病提供初步的理论基础。

Negative emotions are ubiquitous in the animal kingdom. In human, persistent negative emotions could cause a series of mental disorder and diseases, such as depression and anxiety disorders. Limited by experimental approaches, both the neural circuitry of negative emotions and their effects on cognation are elusive. Our preliminary data suggested that male fruit flies exhibit loser effects after defeated in a combat, and the male flies showed disgust behavior to other flies after being courted mistakenly by other males. In both cases, the negative effects last for hours and exhibit suppressive influences over a broad range of behaviors. Therefore, our paradigms provide a long-sought-after entry point to study negative emotions on their neural circuits and effects on learning and memory. We propose to use molecular genetics and quantitative behavioral analysis to systematically investigate the negative emotions. Our study would lead to better understanding on the interactions of emotion and cognation at multiple levels, and provide basic knowledge for understanding neurological and psychological disorders in human.