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.
journal_name
Elifejournal_title
eLifeauthors
Scheimann JR,Moloney RD,Mahbod P,Morano RL,Fitzgerald M,Hoskins O,Packard BA,Cotella EM,Hu YC,Herman JPdoi
10.7554/eLife.44672subject
Has Abstractpub_date
2019-07-22 00:00:00issn
2050-084Xpii
44672journal_volume
8pub_type
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