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 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.
Kolber
Benedict J
BJ
Department of Pediatrics, Washington University, St. Louis, MO 63110, USA.
Roberts
Marie S
MS
Howell
Maureen P
MP
Wozniak
David F
DF
Sands
Mark S
MS
Muglia
Louis J
LJ
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003346:Corticotropin-Releasing Hormone