Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/44672 |
| _version_ | 1828380223617368064 |
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| author | Jessie R Scheimann Rachel D Moloney Parinaz Mahbod Rachel L Morano Maureen Fitzgerald Olivia Hoskins Benjamin A Packard Evelin M Cotella Yueh-Chiang Hu James P Herman |
| author_facet | Jessie R Scheimann Rachel D Moloney Parinaz Mahbod Rachel L Morano Maureen Fitzgerald Olivia Hoskins Benjamin A Packard Evelin M Cotella Yueh-Chiang Hu James P Herman |
| author_sort | Jessie R Scheimann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:53:08Z |
| format | Article |
| id | doaj.art-f9a00f4e02414ddb96a45b0f09742316 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:53:08Z |
| publishDate | 2019-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f9a00f4e02414ddb96a45b0f097423162022-12-22T02:03:12ZengeLife Sciences Publications LtdeLife2050-084X2019-07-01810.7554/eLife.44672Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviorsJessie R Scheimann0https://orcid.org/0000-0001-7912-4898Rachel D Moloney1https://orcid.org/0000-0001-7111-3414Parinaz Mahbod2Rachel L Morano3Maureen Fitzgerald4Olivia Hoskins5Benjamin A Packard6Evelin M Cotella7Yueh-Chiang Hu8James P Herman9Department Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesDivision of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, United States; Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United StatesDepartment Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, United StatesGlucocorticoid 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.https://elifesciences.org/articles/44672CRISPR/Cas9glucocorticoid receptorSprague Dawleyprefrontal cortexsex difference |
| spellingShingle | Jessie R Scheimann Rachel D Moloney Parinaz Mahbod Rachel L Morano Maureen Fitzgerald Olivia Hoskins Benjamin A Packard Evelin M Cotella Yueh-Chiang Hu James P Herman Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors eLife CRISPR/Cas9 glucocorticoid receptor Sprague Dawley prefrontal cortex sex difference |
| title | Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors |
| title_full | Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors |
| title_fullStr | Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors |
| title_full_unstemmed | Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors |
| title_short | Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors |
| title_sort | conditional deletion of glucocorticoid receptors in rat brain results in sex specific deficits in fear and coping behaviors |
| topic | CRISPR/Cas9 glucocorticoid receptor Sprague Dawley prefrontal cortex sex difference |
| url | https://elifesciences.org/articles/44672 |
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