Effects of chronic stress on amygdala physiology

描述（由申请人提供）：压力影响广泛的行为，长时间的压力会诱发或加剧精神疾病。据信，压力对青少年的影响比成年人大。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对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的关系。这项提议检验了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的假设，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）定量体内和体外慢性应激对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）定量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，以及4）比较青春期和成年期慢性应激的这些影响。这将使用在体内和体外的电生理记录和单细胞钙成像的杏仁核神经元在慢性应激模型的组合进行研究。将对膜兴奋性的测量和巴甫洛夫恐惧条件反射的行为测量进行量化，并采用双因素ANOVA和适当的事后比较在组间进行比较。慢性应激可通过一种特殊的神经病理机制使杏仁核神经元兴奋性增加，并使杏仁核依赖性行为加重，且这种作用在青春期比成年期更明显。这项研究可以证明一种机制，即压力增加情感行为的年龄依赖性的方式。通过了解慢性压力的影响及其年龄依赖性，人们可以潜在地了解一种预防或逆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会导致精神疾病，对儿童尤其有害。这项研究将检验慢性压力是否会对幼年动物大脑中与情绪行为有关的杏仁核区域产生更大的影响。这将有助于了解为什么青少年更容易受到压力的影响，从而采取适合其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.