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Author Notes:

Correspondence to: Shannon L Gourley; Email: shannon.l.gourley@emory.edu

Acknowledgments: Authors thank Ms. Amanda Allen for her assistance with processing dendritic spine images and data.

Disclosures: No potential conflicts of interest were disclosed.

Subjects:

Research Funding:

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:

  • RU486
  • mifepristone
  • stress
  • corticosterone
  • habit
  • outcome

Glucocorticoid receptor regulation of action selection and prefrontal cortical dendritic spines

Tools:

Journal Title:

Communicative and Integrative Biology

Volume:

Volume 6, Number 6

Publisher:

, Pages e26068-e26068

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2013 Landes Bioscience

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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