Effects of chronic stress on amygdala physiology

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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.