TY - JOUR TI - Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors AU - Scheimann, Jessie R AU - Moloney, Rachel D AU - Mahbod, Parinaz AU - Morano, Rachel L AU - Fitzgerald, Maureen AU - Hoskins, Olivia AU - Packard, Benjamin A AU - Cotella, Evelin M AU - Hu, Yueh-Chiang AU - Herman, James P A2 - Schoenbaum, Geoffrey A2 - Dulac, Catherine A2 - Harvey, Brandon K A2 - Sandi, Carmen VL - 8 PY - 2019 DA - 2019/07/22 SP - e44672 C1 - eLife 2019;8:e44672 DO - 10.7554/eLife.44672 UR - https://doi.org/10.7554/eLife.44672 AB - 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. KW - CRISPR/Cas9 KW - glucocorticoid receptor KW - Sprague Dawley KW - prefrontal cortex KW - sex difference JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -