恐惧和应激密不可分，室旁核的肾上腺皮质激素释放激素(CRH)神经元在应激过程中起关键作用，但在恐惧记忆中的作用尚不清楚。前期研究发现室旁核投射到基底外侧核（BLA）的CRH神经纤维，光激活CRH神经元影响恐惧行为。我们假设：在习得性恐惧反应中下丘脑室旁核CRH神经元激活，其投射到BLA的神经纤维末梢释放出CRH，通过其受体CRHR1兴奋BLA的谷氨酸能神经元，进而兴奋杏仁核中央外侧核 的I型神经元，增强僵立等恐惧行为反应，促进恐惧记忆的形成和表达。本实验拟采用光敏通道调控的 CRH 转基因鼠，描绘下丘脑室旁核与杏仁核的CRH神经环路连接并阐述其对习得性恐惧记忆过程的影响；揭示下丘脑室旁核CRH神经元对基底外侧杏仁核突触传递的影响及其机制；确定CRH通过其表达于BLA的受体CRHR1对谷氨酸合成和释放的影响及其分子机制；期望阐述下丘脑室旁核CRH神经元通过调控杏仁核参与恐惧记忆的作用和机制。

Fear and stress are inseparable. Corticotropin-releasing hormone (CRH) neurons are mainly distributed in the paraventricular nucleus (PVN) and play a key role in the stress response. But it is unclear about the role in fear memory. Preliminary data showed that CRH neural fibers in BLA orginated from PVN to and by using optogenetic tools to activate CRH neurons in PVN it affected fear response in mice. Thus we hypothesize that CRH neural circuit between hypothalamus and amygdala play an important role in conditioned fear. Basically, in conditioned fear response, CRH neurons projecting from PVN to basolateral nucleus of amygdala are activated and CRH was released from the terminals to act on glutamatergic neurons in BLA via CRHR1, then excite type I neurons in lateral central amygdala (CEl) and enhance freezing behavior, and promote the formation and expression of conditioned fear. By using CRH transgenic model animals which express ChR2 or NpHR, we aim to depict CRH neural circuits between PVN and amygdala and investigate the role in conditioned fear, to investigate the effect of CRH neurons in PVN on the synaptic transmission in BLA and its mechanism, to determine its effect on glutamate synthesis and release via CRHR1, to elucidate the role of CRH neurons in PVN involved in the regulation of conditioned fear via modulating amygdala.