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.
Exposure to major adverse events has profound effects on organismic functioning, and is an important etiological factor in the development of psychiatric disorders. Thus, it is critical to identify factors that leas to resilience in the face of such events, and the brain mechanisms by which resilience is produced. The proposed research is directed a these issues.
|Baratta, Michael V; Leslie, Nathan R; Fallon, Isabella P et al. (2018) Behavioural and neural sequelae of stressor exposure are not modulated by controllability in females. Eur J Neurosci 47:959-967|
|Dolzani, S D; Baratta, M V; Moss, J M et al. (2018) Inhibition of a Descending Prefrontal Circuit Prevents Ketamine-Induced Stress Resilience in Females. eNeuro 5:|
|Amat, Jose; Dolzani, Samuel D; Tilden, Scott et al. (2016) Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress. J Neurosci 36:153-61|
|Fonken, Laura K; Weber, Michael D; Daut, Rachel A et al. (2016) Stress-induced neuroinflammatory priming is time of day dependent. Psychoneuroendocrinology 66:82-90|
|Maier, Steven F; Seligman, Martin E P (2016) Learned helplessness at fifty: Insights from neuroscience. Psychol Rev 123:349-67|
|Maier, Steven F (2015) Behavioral control blunts reactions to contemporaneous and future adverse events: medial prefrontal cortex plasticity and a corticostriatal network. Neurobiol Stress 1:12-22|
|Amat, Jose; Christianson, John P; Aleksejev, Roman M et al. (2014) Control over a stressor involves the posterior dorsal striatum and the act/outcome circuit. Eur J Neurosci 40:2352-8|
|Christianson, John P; Flyer-Adams, Johanna G; Drugan, Robert C et al. (2014) Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex. Front Behav Neurosci 8:348|
|Christianson, John P; Drugan, Robert C; Flyer, Johanna G et al. (2013) Anxiogenic effects of brief swim stress are sensitive to stress history. Prog Neuropsychopharmacol Biol Psychiatry 44:17-22|
|Rozeske, Robert R; Der-Avakian, Andre; Watkins, Linda R et al. (2012) Activation of the medial prefrontal cortex by escapable stress is necessary for protection against subsequent inescapable stress-induced potentiation of morphine conditioned place preference. Eur J Neurosci 35:160-5|
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