适度的恐惧学习与消退促进生物体生存繁衍，过度的恐惧反应与创伤后应激障碍等精神疾病的发生密切相关，内侧前额叶皮层（mPFC）在其中发挥着重要作用，但分子机理尚不明确。小G蛋白Rap1（Rap1a和Rap1b）是调控恐惧学习与记忆的重要信号分子，这与其调节皮层神经元谷氨酸递质释放有关。我们的研究表明，前脑限制性敲除Rap1b特异性损害了小鼠的恐惧学习，而敲除Rap1a则促进小鼠的恐惧消退，提示两者对恐惧学习和消退产生差异化调控，但具体机制不清楚。本项目中，我们拟探究恐惧学习和消退过程中：1）mPFC内Rap1a和Rap1b表达和蛋白活性动态变化；2）Rap1a和Rap1b对mPFC神经元活动的调节作用；3）局部敲除和重表达Rap1a和Rap1b对恐惧学习和消退的可能影响；以期阐明Rap1a和Rap1b差异化调控恐惧学习及消退中作用机制。

Moderate fear learning and extinction is a survival mechanism of organisms, while excessive fear response leads to mental disorders. Medial prefrontal cortex (mPFC) is critical in fear learning and extinction. However, the underlying molecular mechanisms remain largely unknown. The small G protein Rap1 (Rap1a and Rap1b) plays important roles in fear learning and memory, via regulating presynaptic glutamate release of cortical neurons. We have recently identified that forebrain-specific deletion of Rap1b impairs fear learning, while deletion of Rap1a promotes fear extinction, suggesting differential roles of two members. However, the mechanisms underlying the distinct roles of Rap1a and Rap1b are not well understood. To address related questions, we will perform the following studies: 1) Dynamic changes of Rap1a and Rap1b expression and activity in mPFC during fear learning and extinction; 2) Regulatory effects of Rap1a and Rap1b on activity of mPFC neurons; 3) Changes in fear learning and extinction by knockout and re-expression of Rap1a and Rap1b in mPFC. The findings will benefit the understanding of how Rap1a and Rap1b differentially regulate fear learning and extinction.