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

为什么有些人能在紧张的情况下迅速反应，冷静下来，清晰地思考，而另一些人却因恐惧和焦虑而动弹不得？幼儿时期的经历对这些情绪和认知应对行为的个体差异负有责任吗？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。虽然很明显，经历过创伤性事件的儿童在学习和应对方面有困难，但关于补偿机制和早期经历在组织这些途径中的作用的信息却很少。齐默尔伯格教授提出，“压力补偿”系统可能是由神经类固醇3- α -羟基，5- α -孕酮-20- 1（异孕酮）介导的，这是一种黄体酮代谢物，在男性和女性的大脑中合成，以应对压力。她已经证实，这种黄体酮代谢物可以减少年轻人和成年人在新的、紧张的情况下的恐惧行为。新生儿和成人异孕酮调节的应激反应的个体差异被证明受到产前和产后应激经历以及选择性育种的影响。这项资助将通过研究选定脑区域的神经类固醇/GABAa结合参数来阐明早期应激的短期和长期后果的可能机制。这项研究将使我们更好地理解我们在恐惧或压倒性情况下抑制生理反应的能力背后的神经机制，从而使我们能够适应并发展出更冷静、更有说服力的反应。在一个压力经常导致愤怒的社会中，了解对压力的基本生物反应及其控制将对教育者、父母和公共政策制定者有广泛的好处。齐默尔伯格博士即将辞去一所小型本科学院的主要行政和课程要求，在职业生涯的关键中期阶段，齐默尔伯格博士将延长对两所主办机构的访问时间，组织POWRE活动，以提升她的教学和研究水平。在埃默里大学（Emory University）的行为神经科学中心，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。

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.