Stressor controllability: Prefrontal circuits that produce resilience and dominance

Project Summary/Abstract The degree of behavioral control that an organism (rodent to human) can exert over an adverse event is arguably the most potent variable yet discovered that modulates the 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, that is, control produces future resilience in the face of adversity. Research over the past grant period has indicated that control does so by activating distinct circuits within the prelimbic (PL) region of the medial prefrontal cortex that process separable features of control. One, a corticostriatal circuit that detects the contingency between the instrumental controlling response (action) and stressor termination (outcome) and another, a prefrontal-to-brainstem projection, that subsequently uses control information to inhibit stress-responsive structures, thereby blunting the impact of the stressor. Data also suggest a potential role for the mediodorsal thalamus (MDT) in detecting control and serving as a substrate for communication between the above circuits. Moreover, we have found that the experiences of behavioral control and social dominance engage similar PL circuitry in producing resilience to future nonsocial stressors. Thus, the present proposal focuses on the mechanisms by which behavioral control (Aim 1) and social dominance (Aim II) produce resilience/resistance against future stressors. Finally, the protective effects of behavioral control and winning are completely absent in females and Aim III seeks to determine exactly how PL circuitry may respond differently between the sexes.