Neural System of Fear and Stress

恐惧和压力的神经系统

• 批准号: 6850590
• 负责人: JOSEPH E LEDOUX
• 金额: $ 38.37万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6850590
• 关键词: amygdala; behavioral /social science research tag; brain electrical activity; brain mapping; clinical research; conditioning; coping; dendrites; fear; gender difference; glucocorticoids; hormone regulation /control mechanism; human subject; hypothalamic pituitary adrenal axis; laboratory rat; memory; neural plasticity; neuropsychology; patient oriented research; posttraumatic stress disorder; psychopharmacology; stress

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.

授予=P50MH58911-06-0005 项目 1 的重点是老鼠和人类的正常恐惧机制，以及压力对这些机制的影响。所有研究都涉及与中心其他成员的互动，如下所述。提出了六项大鼠研究。研究 1 研究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中的作用将被确定。研究2评估压力对恐惧的影响是否是由于杏仁核或条件性恐惧回路的其他区域（内侧前额叶皮层、海马体、终纹床核）中压力激素的作用所致。研究 3 评估了压力和压力激素对杏仁核细胞生理学及其可塑性的影响。 研究 4 检查压力和/或恐惧调节在多大程度上引起杏仁核树突形态或脊柱组织的结构变化，并检查介导结构变化的分子机制。研究 5 继续开展有关 SSRI 等中介调节条件性恐惧机制的项目。研究 6 探讨了恐惧的重新巩固，试图通过动物研究来确定在记忆检索过程中安全实用的药物制剂，以阻止以后的生存和/或获取创伤性记忆。人体研究由纽约大学的伊丽莎白·菲尔普斯领导。这些结果将纳入项目 2 的新患者研究设计中。研究 1 基于上述大鼠研究的想法，并检查特质焦虑、HPA 反应或对急性大脑激活模式的反应是否存在个体或性别差异。高焦虑个体和低焦虑个体在恐惧调节和积极应对过程中存在差异。研究 3 检查了焦虑症患者的积极应对方式。研究 4 和 5 探讨了在检索过程中对记忆进行药物操纵可能会改变记忆的存活或可访问性的可能性，因此可能有助于治疗 PTSD 的创伤性记忆症状。