Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning
Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning
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DOI：
10.1073/pnas.0803216105
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发表时间：
2008-08-19
影响因子：
11.1
通讯作者：
Muglia, Louis J.
中科院分区：
文献类型：
--
作者：
Kolber, Benedict J.;Roberts, Marie S.;Muglia, Louis J.
杏仁核是参与恐惧反应和巴甫洛夫条件反射的关键边缘区域，有可能直接对与恐惧或压力相关的内分泌信号做出反应。为了深入了解恐惧条件作用的分子机制和亚区特异性，我们通过将含有Cre重组酶的慢病毒载体导入FLOXED-GR小鼠体内，破坏了杏仁中央核(CEA)中的11型糖皮质激素受体(GRs)。CEA(CeAGRKO小鼠)中的GR缺失阻止了条件性恐惧行为。相比之下，不包括CEA的GRs的前脑中断则没有。CeAGRKO小鼠的条件性恐惧缺陷与CFO和促肾上腺皮质激素释放激素(CRH)表达的减少有关。此外，脑室注射CRH挽救了CeAGRKO小鼠的条件性恐惧缺陷。我们得出结论，恐惧条件作用涉及神经内分泌回路，通过激活CEA中的GR来诱导急性CRH和持久的行为调节。
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.