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.

赠款= P50MH58911-06-0005 项目1的重点是恐惧的正常机制，以及在大鼠和人类中压力的影响。如下所述，所有研究都涉及与中心其他成员的互动。提出了六项大鼠研究。研究1研究了压力对条件恐惧的影响，包括对个体和性别差异的分析。糖皮质激素在压力对恐惧的介导作用中的作用将得到确定。研究2评估压力对恐惧的影响是否是由于应激激素在杏仁核或条件恐惧回路的其他区域（内侧前额叶皮层，海马，海马，骨膜的床核）的作用。研究3评估应力和应激激素对杏仁核细胞生理的影响及其可塑性。 研究4研究了压力和/或恐惧调节的程度在杏仁核中的树突形态或脊柱组织中导致结构性变化，并研究了介导结构变化的分子机制。研究5继续开展有关SSRIS等调解调节条件恐惧的机制的持续项目。研究6探讨了恐惧的重新整合，以确定动物研究，这些药理学药物在记忆检索过程中安全且可实用，以阻止后来的生存和/或获得创伤性记忆。人类研究由纽约大学的伊丽莎白·菲尔普斯（Elizabeth Phelps）领导。这些结果将带入项目2的新患者研究的设计。研究1基于上面的大鼠研究的思想，并检查特质焦虑，HPA反应或对急性焦虑症患者在恐惧条件和主动应对过程中对急性脑激活模式的反应中的个人或性别差异。研究3检查焦虑症患者的主动应对。研究4和5探讨了在检索过程中对记忆的药理操作可能会改变记忆的生存或可及性的可能性，因此可能有助于治疗PTSD中的创伤性记忆症状。