Neural System of Fear and Stress

恐惧和压力的神经系统

• 批准号: 7490651
• 负责人: JOSEPH E LEDOUX
• 金额: $ 45.71万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490651
• 关键词: Acute; Amygdaloid structure; Animals; Anxiety; Anxiety Disorders; Brain; Cells; Fright; Glucocorticoids; Grant; HPSE gene; Hippocampus (Brain); Hormones; Human; Individual; Medial; Mediating; Mediation; Memory; Molecular; Morphology; Patients; Pattern; Physiology; Post-Traumatic Stress Disorders; Prefrontal Cortex; Rattus; Retrieval; Role; Sex Characteristics; Stress; Structure of terminal stria nuclei of preoptic region; Symptoms; System; Vertebral column; conditioned fear; coping; design; feeding; human study; hypothalamic-pituitary-adrenal axis; member; memory retrieval; relating to nervous system; response; trait

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.

授权= P50 MH 58911 -06-0005 项目1的重点是恐惧的正常机制，以及压力对大鼠和人类的影响。所有研究都涉及与中心其他成员的互动，如下所述。提出了6项大鼠研究。研究1探讨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评估了压力对恐惧的影响是否是由于杏仁核或条件恐惧回路的其他区域（内侧前额叶皮层、海马、终纹床核）中的压力激素的作用。研究3评估了压力和压力激素对杏仁核细胞生理及其可塑性的影响。 研究4探讨了压力和/或恐惧条件反射在杏仁核树突形态或棘组织中产生结构变化的程度，并探讨了介导结构变化的分子机制。研究5继续进行中的项目，研究SSRIs等中介调节条件性恐惧的机制。研究6探讨了恐惧的再巩固，通过动物研究，试图确定在记忆提取过程中安全实用的药理学药物，以阻止以后的生存和/或创伤记忆的访问。人类研究由纽约大学的伊丽莎白·菲尔普斯领导。这些结果将用于项目2的新患者研究设计。研究1建立在上述大鼠研究的基础上，研究了在恐惧条件反射和积极应对过程中，高焦虑和低焦虑个体之间在特质焦虑、HPA反应或对急性脑激活模式的反应方面是否存在个体或性别差异。研究3探讨了焦虑症患者的积极应对。研究4和5探讨了在提取过程中对记忆进行药理学操作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中的创伤性记忆症状。