Sex differences in amygdala function

项目摘要 尽管情绪和焦虑症在女性中的发病率较高，但在性别表达上的差异 症状，情感行为性别差异的神经生物学基础不是很好 明白了。杏仁核功能障碍与这些疾病有关，但尚不清楚是否存在 杏仁核神经元功能的性别差异，或精神病理学中的杏仁核易感性。目标锁定 杏仁核病理的性别差异有望为临床治疗提供一种新的治疗途径。 情感障碍。该项目的目标是测试杏仁核的生理和功能是否存在差异 女性和男性的功能，以及与情绪障碍有共同特征的应激模型是否施加 对杏仁核的性别依赖效应。这个项目将检验中心假说，即基准面 女性的杏仁核(BLA)比男性的BLA反应更灵敏，这种差异是 BLA神经元的亚回路，这种应激降低了女性BLA神经元的兴奋性和功能， 但对男性的血乳酸功能有相反的影响。该项目将测试离子通道的贡献， 调节BLA神经元对性别差异的兴奋性，以及调节这些酶功能的关键酶 离子通道。此外，该项目还将测试这些新离子的药理操作是否 通道和酶靶标可以逆转压力对行为的影响。这些研究的基本原理是 杏仁核依赖行为性别差异的机制及应激对其的影响 行为尚不清楚。需要了解这些问题，才能确定杏仁核在性行为中的作用 情绪障碍症状的差异。这项提议的目的是测试血乳酸中的性别差异 如果重复应激对BLA功能的影响是性别的，那么神经元的兴奋性是BLA亚回路特有的 依赖，以及这种影响是否可以以性别依赖的方式逆转。这将在体内进行测试，并 体外电生理方法，结合生化和行为方法。这些目标 有望证明血乳酸的生理性别差异，反复应激对血乳酸的影响 生理和功能，而针对应激影响的药物靶向将逆转 一种性别依赖的方式。这可能导致对情绪和焦虑性别差异原因的新见解 并导致了一种新的性别依赖的治疗方法，用于快速治疗情绪障碍。

Project Summary Despite a higher incidence of mood and anxiety disorders in females, and sex differences in the expression of symptoms, the neurobiological underpinnings of sex differences in affective behaviors are not well understood. Dysfunction of the amygdala contributes to these disorders, yet it is unknown whether there are sex differences in amygdala neuronal function, or in amygdala susceptibility in psychopathology. Targeting of sex differences in amygdala pathology is expected to provide a novel therapeutic approach for the treatment of affective disorders. The objective of this project is to test whether differences exist in amygdala physiology and function in females and males, and whether a stress model that shares features with mood disorders exerts sex-dependent effects on the amygdala. This project will test the central hypothesis that the basolateral amygdala (BLA) in females is more responsive than the BLA in males, that this difference is specific for subcircuits of BLA neurons, and that stress decreases neuronal excitability and function of the BLA in females, but exerts opposite effects on BLA function in males. This project will test the contribution of ion channels that regulate BLA neuronal excitability to the sex differences, and key enzymes that modulate the function of these ion channels. In addition, this project will also test whether pharmacological manipulation of these novel ion channel and enzymatic targets reverses the behavioral impact of stress. The rationale for these studies is that the mechanism for sex differences in amygdala-dependent behaviors and the impact of stress on these behaviors is not known. These issues need to be understood to determine the role of the amygdala in sex differences in mood disorder symptomology. The Aims of this proposal are to test if sex differences in BLA neuronal excitability is specific for BLA subcircuits, if the effects of repeated stress on BLA function are sex dependent, and if the effects can be reversed in a sex-dependent manner. This will be tested using in vivo and in vitro electrophysiological approaches, combined with biochemical and behavioral approaches. These Aims are expected to demonstrate sex differences in the physiology of the BLA, the effects of repeated stress on BLA physiology and function, and that pharmacological targeting of the effects of stress will reverse impairments in a sex-dependent manner. This can lead to novel insight into the cause of sex differences in mood and anxiety disorders, and lead to a novel sex-dependent therapeutic approach for rapid treatment of mood disorders.