强烈的恐惧记忆与创伤后应激障碍（PTSD）的发病密切相关。促肾上腺皮质激素释放因子（CRF）是机体应激反应的中枢驱动力，在调控恐惧反应中扮演重要角色。前内侧丘脑（Anteromedial thalamus）调控恐惧记忆的研究较少，机制不清。申请人前期预实验结果显示CRF神经元在前内侧丘脑大量表达，提高CRF神经元的活性增强线索依赖的恐惧记忆。本项目将以CRF转基因小鼠为研究对象，利用在体钙离子成像、神经环路示踪、脑片膜片钳、光遗传学和化学遗传学技术，解析前内侧丘脑CRF神经元编码线索依赖的恐惧记忆的模式，揭示前内侧丘脑CRF神经元经内侧前额叶环路，增强线索依赖的恐惧记忆的机制；旨在进一步明确条件性恐惧记忆的内在神经环路基础，为包括PTSD在内的情感障碍的治疗提供新思路和可能干预位点。

Traumatic fear memory is closed involved in the development of posttraumatic stress disorder (PTSD). Corticotropin-releasing factor (CRF) is widely regarded as the central driving factor of stress response and plays a key role in the regulation of fear response. Less attention has been paid to the role of anteromedial thalamus (AM) in fear memory and the mechanism remains unclear. Preliminary data showed that CRF neurons were distributed in the anteromedial thalamus, and increasing CRF neuronal activity enhanced cued-dependent fear memory. Here, this project intends to combine calcium imaging in vivo, neural circuit tracing, patch-clamp recording in vitro, optogenetics and chemogenetics to identify the mechanism of CRF neurons in the AM coding cued-dependent fear memory in the CRF transgenic mice. Furthermore, this work will elucidate the structural and functional bases of CRF neurons in the AM involved in the increase of cued-dependent fear response via modulating the activity of medial prefrontal cortex. The project aims to further uncover the intrinsic neural circuit mechanism underlying conditioned fear memory and to provide the new theoretical basis and potential interventional target for the treatment of stress-related affective disorders including PTSD.