Glucocorticoid receptor regulation of action selection and prefrontal cortical dendritic spines

• Type of Material: Article
• Authors: Andrew M. Swanson, Emory University; Lauren P Shapiro, Emory University; Alonzo J Whyte, Emory University; Shannon L Gourley, Emory University
• Language: English
• Date: 2013-11-01
• Publisher: Landes Bioscience: OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Landes Bioscience
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): https://www.landesbioscience.com/journals/cib/article/26068/
• Title of Journal or Parent Work: Communicative and Integrative Biology
• ISSN: 1942-0889
• Volume: 6
• Issue: 6
• Start Page: e26068
• End Page: e26068
• Grant/Funding Information: This work was supported by Children’s Healthcare of Atlanta, the Emory Egleston Children’s Research Center, and the Brain and Behavior Research Foundation (Dr. Gourley is the Foundation’s Katherine Deschner Family New Investigator).; The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD11132.
• Keywords: outcome; habit; RU486; mifepristone; stress; corticosterone
• Research Categories: Health Sciences, General; Biology, Cell; Psychology, Psychobiology

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.