Neural System of Fear and Stress

格兰特=P50MH58911-06-0005 项目1的重点是恐惧的正常机制，以及压力对这些机制的影响，无论是对大鼠还是对人类。所有研究都涉及与中心其他成员的互动，如下所述。有六项老鼠研究被提出。研究1考察了压力对条件性恐惧的影响，包括对个体和性别差异的分析。糖皮质激素在调节压力对恐惧的影响方面的作用将被确定。研究2评估了压力对恐惧的影响是否源于杏仁核或条件恐惧回路的其他区域(内侧前额叶皮质、海马体、终纹床核)的压力荷尔蒙的作用。研究3评估了应激和应激激素对杏仁核细胞的生理及其可塑性的影响。研究4考察了应激和/或恐惧条件作用在多大程度上导致杏仁核树突状细胞形态或棘突组织的结构变化，并研究了调节结构变化的分子机制。研究5继续进行关于SSRI等调节条件性恐惧的中介机制的项目。研究6探讨了恐惧的再巩固，试图通过动物实验确定在记忆恢复过程中使用的安全和实用的药理学药物，以努力阻止以后的存活和/或获得创伤记忆。这项人体研究由纽约大学的伊丽莎白·菲尔普斯领导。这些结果将提供给项目2的新患者研究的设计。研究1建立在上述大鼠研究的思想基础上，并考察在恐惧条件反射和积极应对期间，高焦虑和低焦虑个体在特质焦虑、HPA反应或对急性大脑激活模式的反应方面是否存在个体或性别差异。研究3考察焦虑症患者的积极应对方式。研究4和5探索了在提取过程中对记忆的药物操作可能会改变记忆的存活率或可获得性，从而可能对治疗创伤后应激障碍的创伤性记忆症状有用。

GRANT=P50MH58911-06-0005 The focus of Project 1 is on the normal mechanisms of fear, and the effects of stress on these in both rats and humans. All studies involve interactions with other members of the Center, as described below. Six rat studies are proposed. Study 1 examines the effects of stress on conditioned fear, including an analysis of individual and sex differences. The role of glucocorticoids in mediating effects of stress on fear will be determined. Study 2 assesses whether the effects of stress on fear are due to actions of stress hormones in the amygdala or other regions of the conditioned fear circuitry (medial prefrontal cortex, hippocampus, bed nucleus of the stria terminalis). Study 3 evaluates the effects of stress and stress hormones on the physiology of the amygdala cells and their plasticity. Study 4 examines the extent to which stress and/or fear conditioning produce structural changes in dendritic morphology or spine organization in the amygdala, and examines the molecular mechanisms mediating structural changes. Study 5 continues on-going projects on the mechanisms by which mediations like SSRIs regulate conditioned fear. Study 6 explores reconsolidation of fear in an effort to identify, though animal studies, pharmacological agents that are safe and practical to use during memory retrieval in an effort to block the later survival and/or access to traumatic memories. The human studies are led by Elizabeth Phelps of NYU. Results of these will feed into the design of new patient studies for Project 2. Study 1 builds upon the ideas from the rat studies above and examines whether individual or sex differences in trait anxiety, HPA response, or in the response to acute brain activation patterns different between high and low anxious individuals during fear conditioning and active coping. Study 3 examines active coping in patients with anxiety disorders. Studies 4 and 5 explore the possibility that pharmacological manipulation of memory during retrieval might alter the survival or accessibility of memory and thus might be useful in treating traumatic memory symptoms in PTSD.