title: Glucocorticoid receptor regulation of action selection and prefrontal cortical dendritic spines.
abstract: We recently reported that prolonged exposure to the glucocorticoid receptor (GR) ligand corticosterone impairs decision-making that is dependent on the predictive relationship between an action and its outcome (Gourley et al.; Proceedings of the National Academy of Sciences, 2012). Additionally, acute GR blockade, when paired with action-outcome conditioning, also blocks new learning. We then showed that dendritic spines in the prelimbic prefrontal cortex remodeled under both conditions. Nonetheless, the relationship between deep-layer dendritic spines and outcome-based decision-making remains opaque. We report here that a history of prolonged corticosterone exposure increases dendritic spine density in deep-layer prelimbic cortex. When spines are imaged simultaneously with corticosteroid exposure (i.e., without a washout period), dendritic spine densities are, however, reduced. Thus, the morphological response of deep-layer prelimbic cortical neurons to prolonged corticosteroid exposure may be quite dynamic, with spine elimination during a period of chronic exposure and spine proliferation during a subsequent washout period. We provide evidence, using a Rho-kinase inhibitor, that GR-mediated dendritic spine remodeling is causally related to complex decision-making. Finally, we conclude this report with evidence that a history of early-life (adolescent) GR blockade, unlike acute blockade in adulthood, enhances subsequent outcome-based decision-making. Together, our findings suggest that physiological levels of GR binding enable an organism to learn about the predictive relationship between an action and its outcome, but a history of GR blockade may, under some circumstances, also have beneficial consequences.
authors.affiliation: Department of Pediatrics; Emory School of Medicine; Atlanta, GA USA ; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA ; Graduate Program in Neuroscience; Emory University; Atlanta, GA USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Swanson
authors.affiliation: Department of Pediatrics; Emory School of Medicine; Atlanta, GA USA ; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA ; Molecular and Systems Pharmacology; Emory University; Atlanta, GA USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shapiro
authors.affiliation: Department of Pediatrics; Emory School of Medicine; Atlanta, GA USA ; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA.
authors.forename: Alonzo J
authors.initials: AJ
authors.lastname: Whyte
authors.affiliation: Department of Pediatrics; Emory School of Medicine; Atlanta, GA USA ; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA ; Graduate Program in Neuroscience; Emory University; Atlanta, GA USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Gourley
keywords: RU486; corticosterone; habit; mifepristone; outcome; stress