Effects of chronic stress on amygdala physiology

慢性压力对杏仁核生理的影响

• 批准号: 8067177
• 负责人: Jeremy E Rosenkranz
• 金额: $ 34.3万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-07 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8067177
• 关键词: Adolescence; Adolescent; Adult; Affect; Affective; Age; Amygdaloid structure; Anxiety; Behavior; Behavioral; Brain region; Calcium; Cells; Child; Chronic stress; Conflict (Psychology); Data; Dependency; Emotional; Emotions; Endocrine; Environment; Exposure to; Goals; Image; In Vitro; Ion Channel; Ions; Lead; Learning; Measurement; Measures; Membrane; Mental Depression; Mental disorders; Modeling; Modification; Morphology; Neurons; Physiology; Production; Property; Rattus; Research; Schizophrenia; Stress; Synapses; Testing; Whole-Cell Recordings; age group; age related; behavior measurement; classical conditioning; conditioned fear; disability; in vivo; indexing; insight; juvenile animal; neuronal excitability; novel; prevent; restraint stress; therapy development

DESCRIPTION (provided by applicant): Stress influences a wide range of behaviors, and prolonged stress can induce or exacerbate psychiatric disorders. Stress is believed to exert a greater impact in adolescents than adults. One target for the effects of stress on behavior is the amygdala, a brain region involved with the production of emotion. The goal of this research is to understand the impact of prolonged stress on behavior. Specifically, the short term goal is to understand how chronic stress affects behavior through actions on amygdala neurons, and how this relates to age-dependent effects of stress. This proposal examines the hypothesis that chronic stress exaggerates affective behavior by increasing the excitability of amygdala neurons, and that this effect is greater in adolescence. This hypothesis will be tested by 1) quantifying the effects of chonic stress on amygdala neuronal excitability in vivo and in vitro, 2) determining the underlying disruption of ion channels, 3) quantifying the effects of chronic stress on amygdala neuronal integration and amygdala-dependent behaviors, such as Pavlovian conditioning, and 4) comparing these effects of chronic stress between adolescence and adulthood. This will be studied using a combination of in vivo and in vitro electrophysiological recordings and single-cell calcium imaging of amygdala neurons in a chronic stress model. Measures of membrane excitability and behavioral measures of Pavlovian fear conditioning will be quantified, and compared between groups with a 2-way ANOVA and appropriate post-hoc comparisons. It is expected that chronic stress will increase the excitability of amygdala neurons by a specific chennelopathy, and exaggerate amygdala-dependent behaviors, and this effect will be greater in adolescence than adulthood. This study can demonstrate a mechanism whereby stress increases affective behaviors in an age-dependent manner. By understanding the effects of chronic stress, and its age-dependency, one can potentially gain insight into a means to prevent or reverse stress-induced deficiencies in different age groups. Chronic stress, such as abuse and conflict, can contribute to psychiatric disorders, and can be particularly harmful in children. This study will examine if chronic stress exerts a bigger effect in young animals on a brain region involved with emotional behavior, the amygdala. This would provide an understanding of why adolescents are more vulnerable to some effects of stress, which can lead to age-appropriate preventative or curative measures.

描述（由申请人提供）：压力会影响多种行为，长期压力会诱发或加剧精神疾病。人们认为压力对青少年的影响比成年人更大。压力对行为影响的一个目标是杏仁核，这是一个与情绪产生有关的大脑区域。这项研究的目的是了解长期压力对行为的影响。具体来说，短期目标是了解慢性压力如何通过杏仁核神经元的作用影响行为，以及这与压力的年龄依赖性影响有何关系。该提案检验了这样的假设：慢性压力通过增加杏仁核神经元的兴奋性来夸大情感行为，并且这种影响在青春期更大。该假设将通过以下方式进行检验：1) 量化慢性应激对体内和体外杏仁核神经元兴奋性的影响，2) 确定离子通道的潜在破坏，3) 量化慢性应激对杏仁核神经元整合和杏仁核依赖性行为（如巴甫洛夫条件反射）的影响，4) 比较慢性应激的这些影响 青春期和成年之间的压力。将在慢性应激模型中结合体内和体外电生理记录以及杏仁核神经元的单细胞钙成像来研究这一点。膜兴奋性的测量和巴甫洛夫恐惧调节的行为测量将被量化，并通过双向方差分析和适当的事后比较在组之间进行比较。预计慢性压力会通过特定的陈氏病增加杏仁核神经元的兴奋性，并夸大杏仁核依赖性行为，并且这种影响在青春期会比成年期更大。这项研究可以证明压力以与年龄相关的方式增加情感行为的机制。通过了解慢性压力的影响及其年龄依赖性，人们有可能深入了解一种预防或扭转不同年龄组压力引起的缺陷的方法。虐待和冲突等慢性压力可能导致精神疾病，对儿童尤其有害。这项研究将检查慢性压力是否对幼年动物大脑中与情绪行为有关的区域——杏仁核——产生更大的影响。这将有助于理解为什么青少年更容易受到某些压力的影响，从而可以采取适合年龄的预防或治疗措施。