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Elife. 2019 Jul 22;8. pii: e44672. doi: 10.7554/eLife.44672.

Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors.

Author information

1
Department Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United States.
2
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
3
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, United States.
4
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
#
Contributed equally

Abstract

Glucocorticoid receptors (GR) have diverse functions relevant to maintenance of homeostasis and adaptation to environmental challenges. Understanding the importance of tissue-specific GR function in physiology and behavior has been hampered by near-ubiquitous localization in brain and body. Here we use CRISPR/Cas9 gene editing to create a conditional GR knockdown in Sprague Dawley rats. To test the impact of cell- and region-specific GR knockdown on physiology and behavior, we targeted GR knockdown to output neurons of the prelimbic cortex. Prelimbic knockdown of GR in females caused deficits in acquisition and extinction of fear memory during auditory fear conditioning, whereas males exhibited enhanced active-coping behavior during forced swim. Our data support the utility of this conditional knockdown rat to afford high-precision knockdown of GR across a variety of contexts, ranging from neuronal depletion to circuit-wide manipulations, leveraging the behavioral tractability and enhanced brain size of the rat as a model organism.

KEYWORDS:

CRISPR/Cas9; Sprague Dawley; glucocorticoid receptor; neuroscience; prefrontal cortex; rat; sex difference

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