Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning

被引:112
作者
Kolber, Benedict J. [1 ,2 ,3 ]
Roberts, Marie S. [4 ,5 ]
Howell, Maureen P. [1 ,2 ,3 ]
Wozniak, David F. [6 ]
Sands, Mark S. [4 ,5 ]
Muglia, Louis J. [1 ,2 ,3 ]
机构
[1] Washington Univ, Dept Pediat, St Louis, MO 63110 USA
[2] Washington Univ, Dept Dev Biol, St Louis, MO 63110 USA
[3] Washington Univ, Program Neurosci, St Louis, MO 63110 USA
[4] Washington Univ, Dept Internal Med, St Louis, MO 63110 USA
[5] Washington Univ, Dept Genet, St Louis, MO 63110 USA
[6] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
adrenal; animal behavior; knockout mice; lentivirus; stress;
D O I
10.1073/pnas.0803216105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 11 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.
引用
收藏
页码:12004 / 12009
页数:6
相关论文
共 33 条
[1]   Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus [J].
Amorapanth, P ;
LeDoux, JE ;
Nader, K .
NATURE NEUROSCIENCE, 2000, 3 (01) :74-79
[2]  
Blomer U, 1997, J VIROL, V71, P6641
[3]   Forebrain glucocorticoid receptors modulate anxiety-associated locomotor activation and adrenal responsiveness [J].
Boyle, MP ;
Kolber, BJ ;
Vogt, SK ;
Wozniak, DF ;
Muglia, LJ .
JOURNAL OF NEUROSCIENCE, 2006, 26 (07) :1971-1978
[4]   Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior [J].
Boyle, MP ;
Brewer, JA ;
Funatsu, M ;
Wozniak, DF ;
Tsien, JZ ;
Izumi, Y ;
Muglia, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (02) :473-478
[5]   T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation [J].
Brewer, JA ;
Khor, B ;
Vogt, SK ;
Muglia, LM ;
Fujiwara, H ;
Haegele, KE ;
Sleckman, BP ;
Muglia, LJ .
NATURE MEDICINE, 2003, 9 (10) :1318-1322
[6]   INVOLVEMENT OF THE CENTRAL NUCLEUS AND BASOLATERAL COMPLEX OF THE AMYGDALA IN FEAR CONDITIONING MEASURED WITH FEAR-POTENTIATED STARTLE IN RATS TRAINED CONCURRENTLY WITH AUDITORY AND VISUAL CONDITIONED-STIMULI [J].
CAMPEAU, S ;
DAVIS, M .
JOURNAL OF NEUROSCIENCE, 1995, 15 (03) :2301-2311
[7]   Glucocorticoid receptor antagonism in the basolateral amygdala and ventral hippocampus interferes with long-term memory of contextual fear [J].
Donley, MP ;
Schulkin, J ;
Rosen, JB .
BEHAVIOURAL BRAIN RESEARCH, 2005, 164 (02) :197-205
[8]   PHARMACOLOGICAL EFFECTS PRODUCED BY INTRACEREBRAL INJECTION OF DRUGS IN THE CONSCIOUS MOUSE [J].
HALEY, TJ ;
MCCORMICK, WG .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1957, 12 (01) :12-15
[9]   Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice [J].
Ho, N ;
Liauw, JA ;
Blaeser, F ;
Wei, F ;
Hanissian, S ;
Muglia, LM ;
Wozniak, DF ;
Nardi, A ;
Arvin, KL ;
Holtzman, DM ;
Linden, DJ ;
Zhuo, M ;
Muglia, LJ ;
Chatila, TA .
JOURNAL OF NEUROSCIENCE, 2000, 20 (17) :6459-6472
[10]   Human CD34+ hematopoietic progenitor cell-directed lentiviral-mediated gene therapy in a xenotransplantation model of lysosomal storage disease [J].
Hofling, AA ;
Devine, S ;
Vogler, C ;
Sands, MS .
MOLECULAR THERAPY, 2004, 9 (06) :856-865