POWRE: Early Experience and Neurosteroid Response to Stress: A Behavioral Neuroscience Laboratory Enhancement Project

为什么有些人在有压力的情况下能迅速做出反应，冷静下来并清晰地思考，而另一些人却因恐惧和焦虑而动弹不得？这些个体在情绪和认知应对行为上的差异是由童年早期的经历造成的吗？尽管人们对身体的生理应激反应了解很多，但关于大脑如何应对压力的证据却很少。虽然经历过创伤事件的儿童显然在学习和应对方面存在困难，但关于补偿机制和早期经验在组织这些途径中的作用的信息很少。齐默伯格教授提出，“压力补偿”系统可能是由神经类固醇3-α-羟基，5-α-孕酮-20-酮(别孕酮)介导的，这是一种在男性和女性大脑中合成的孕酮代谢物，对压力做出反应。她已经证实，这种黄体酮代谢物在年轻和成年受试者中都能减少在新的、有压力的情况下的恐惧行为。在新生儿和成人中，别孕酮调节的应激反应的个体差异被证明受到出生前和出生后的应激经历以及选择性繁殖的影响。这项资助将通过研究选定大脑区域中神经类固醇/GABAA结合参数，阐明早期应激短期和长期后果的一种可能机制。这项研究将有助于更好地理解我们抑制对恐惧或压倒性情况的生理反应的能力的神经机制，以便我们能够适应和发展更平静和更令人信服的反应。在一个压力经常导致愤怒的社会里，了解对压力的基本生物反应及其控制将对教育工作者、家长和公共政策制定者有广泛的好处。POWRE活动是围绕着对两所主办机构的长期访问而组织的，以便让齐默伯格博士能够在职业生涯中期的关键阶段提升她的教学和研究水平。齐默伯格博士即将辞去一所小型本科学院的主要行政和课程任务。在埃默里大学行为神经科学中心，她将掌握新的分子和成像方法，这些方法正在推动行为研究。第二，作为该项目的一部分，将与卡利亚里大学实验神经生物学实验室建立新的国际合作关系。

Why can some people respond quickly in stressful situations, calm down and think clearly, while others are immobilized with fear and anxiety? Are early childhood experiences responsible for these individual differences in emotional and cognitive coping behaviors? Although much is known about the physiological stress responses in the body, there is very little evidence about how the brain responds to stress. And while it is evident that children who experience traumatic events have trouble learning and coping, there is very little information about compensatory mechanisms and the role of early experience in organizing these pathways. Professor Zimmerberg proposes that a "stress compensatory" system may be mediated by the neurosteroid 3-alpha-hydroxy, 5-alpha-pregnan-20-one (allopregnanolone), a progesterone metabolite synthesized in the brains of both males and females in response to stress. She has established that this progesterone metabolite reduces fearful behavior in novel, stressful situations in both young and adult subjects. Individual differences in the allopregnanolone-modulated stress response in neonates and adults were demonstrated to be influenced by both pre- and post-natal stress experiences, as well as by selective breeding. This grant will elucidates one possible mechanism underlying the short and long-term consequences of early stress by studying neurosteroid/GABAa binding parameters in selected brain regions.This research will lead to a better understanding of the neural mechanisms underlying our ability to dampen the physiological responses to fearful or overwhelming situations so we can adapt and develop more calm and cogent reactions. In a society where stress leads too often to rage, understanding the basic biological responses to stress and their control will have broad benefits to educators, parents, and public policy makers.The POWRE activities are organized around extended visits to two host institutions to allow Dr. Zimmerberg, who is stepping down from major administrative and curricular demands at a small undergraduate college, to upgrade her teaching and research at a critical mid-career stage. At the Center for Behavioral Neuroscience at Emory University, she will gain mastery of new molecular and imaging approaches, which are advancing the study of behavior. Second, a new international collaboration with the Laboratory of Experimental Neurobiology at the University of Cagliari will be established as part of this project.