[R01] Stressor controllability: Prefrontal circuits that produce resilience and dominance
Ente: National Institute of Mental Health
Scadenza: 2029-01-31
Importo max: 629.980 EUR
Paese: US
Descrizione
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.
Istituzione: UNIVERSITY OF COLORADO
PI: MICHAEL V BARATTA, STEVEN F MAIER
Progetto: 5R01MH050479-32
Settori: National Institute of Mental Health
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