Project Summary/Abstract The degree of behavioral control that an organism (rodent to human) can exert over an adverse event is one of the most potent variables yet discovered that modulates the behavioral and neurochemical impact of that event. When the organism does have an element of control, the behavioral and neurochemical sequelae of the adverse event are blunted or eliminated. Importantly, the experience of control not only blunts the impact of the stressor being controlled, but also blunts the impact of stressors experienced much later (at least two months in rat), that is, control produces future resilience in the face of adversity. The research to be conducted in this proposal will be directed at investigating the neural circuits by which the prefrontal cortex mediates the stress-buffering effects of coping/control. Specific Aims will examine the precise prefrontal circuits involved in the separable features of behavioral control: (a) the detection of control and (b) the subsequent use of that information to regulate stress-responsive systems accordingly. In addition, over the last grant period we have extended the study of controllability phenomena to females, and surprisingly, here control does not blunt the impact of stress. The proposed research focuses on the roles of specific prefrontal cortex circuits in mediating the effects of control on stress resilience, as well as a determination of exactly how critical prefrontal circuits may respond to stressors differently in males and females.