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

Williams College, Williamstown MA

Investigators

Abstract

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.