Central Amygdala Glucocorticoid Receptor Action Promotes Fear-Associated CRH Activation and Conditioning

The amygdala is a key limbic area involved in fear responses and pavlovian conditioning with the potential to directly respond to endocrine signals associated with fear or stress. To gain insights into the molecular mechanisms and subregional specificity of fear conditioning, we disrupted type II gl...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (33), p.12004-12009
Main Authors: Kolber, Benedict J., Roberts, Marie S., Howell, Maureen P., Wozniak, David F., Sands, Mark S., Muglia, Louis J.
Format: Article
Language:English
Subjects:
Amygdala
Amygdala - drug effects
Amygdala - metabolism
Animals
Behavioral neuroscience
Biological Sciences
Brain
Corticosterone
Corticotropin-Releasing Hormone - pharmacology
Fear
Fear & phobias
Freezing
Gene Deletion
Glucocorticoid receptors
Glucocorticoids
Hormones
Lesions
Memory
Messenger RNA
Mice
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Proteins c-fos - metabolism
Receptors, Glucocorticoid - deficiency
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - metabolism
RNA, Messenger - genetics
Rodents
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Summary:The amygdala is a key limbic area involved in fear responses and pavlovian conditioning with the potential to directly respond to endocrine signals associated with fear or stress. To gain insights into the molecular mechanisms and subregional specificity of fear conditioning, we disrupted type II glucocorticoid receptors (GRs) in the central nucleus of the amygdala (CeA) by delivering lentiviral vectors containing Cre-recombinase into floxed-GR mice. GR deletion in the CeA (CeAGRKO mice) prevented conditioned fear behavior. In contrast, forebrain disruption of GRs excluding the CeA did not. The conditioned fear deficit in CeAGRKO mice was associated with decreases in cFos and corticotropin-releasing hormone (CRH) expression. Moreover, intracerebroventricular delivery of CRH rescued the conditioned fear deficit in CeAGRKO mice. We conclude that fear conditioning involves a neuroendocrine circuit by using GR activation in the CeA for acute CRH induction and long-lasting behavioral modulation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0803216105