Effects of chronic stress on amygdala physiology

描述(由申请人提供)：压力会影响广泛的行为，长期的压力会导致或加剧精神障碍。据信，压力对青少年的影响比成年人更大。压力对行为的影响的一个目标是杏仁核，这是大脑中参与情绪产生的区域。这项研究的目的是了解长期应激对行为的影响。具体地说，短期目标是了解慢性应激如何通过对杏仁核神经元的作用影响行为，以及这与应激的年龄相关效应如何相关。这项建议检验了一种假说，即慢性应激通过增加杏仁核神经元的兴奋性来夸大情感行为，而且这种影响在青春期更大。这一假说将通过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)确定离子通道潜在的干扰，3)量化慢性应激对杏仁核神经元整合和杏仁核依赖行为的影响，如巴甫洛夫条件反射，以及4)比较青春期和成年期慢性应激的影响。这将结合体内和体外的电生理记录和慢性应激模型中杏仁核神经元的单细胞钙成像进行研究。膜兴奋性的测量和巴甫洛夫恐惧条件反射的行为测量将被量化，并用双因素方差分析和适当的组后比较进行组间比较。预计慢性应激会通过一种特定的脑病增加杏仁核神经元的兴奋性，并夸大杏仁核依赖行为，而且这种影响在青春期比成年期更大。这项研究可以证明压力以一种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相关性，人们可以潜在地洞察到一种方法，以防止或扭转不同年龄段的压力诱导的缺陷。长期的压力，如虐待和冲突，可能会导致精神障碍，对儿童的伤害尤其严重。这项研究将研究慢性压力是否会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压力的某些影响，这可能导致适合年龄的预防或治疗措施。

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.