期刊
PSYCHONEUROENDOCRINOLOGY
卷 41, 期 -, 页码 75-88出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2013.12.011
关键词
GABA; Tonic inhibition; CRH neurons; Paraventricular nucleus; Hypothalamus; HPA axis; Stress; Corticosterone; Depression; Anxiety
资金
- Charles H. Hood Foundation Child Health Research Award
- National Institute of Neurological Disorders and Stroke (NINDS) [NS073574, F31 NS078815]
- Tufts Medical Scientist Training Program [T32 GM008448]
The hypothalamic pituitary adrenal (HPA) axis is under tight regulation by strong GABAergic inhibition onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus. CRH neurons receive two forms of GABAergic inhibition, phasic and tonic, but the specific roles of these two types of signaling have not yet been studied in this cell type. Our lab recently demonstrated a role for the GABA(A)R delta subunit in the tonic GABAergic regulation of CRH neurons. Using a floxed Gabrd mouse model established in our laboratory, we generated mice in which the GABA(A)R delta subunit is selectively removed from CRH neurons (Gabrd/Crh mice), resulting in a loss of tonic GABAergic inhibition in these neurons. Interestingly, the loss of this tonic GABAergic constraint did not significantly alter basal levels of corticosterone (CORT). However, the loss of the GABA(A)R delta subunit in CRH neurons blunted the CORT response to stress, likely due to the loss of the disinhibitory effect of GABA following acute stress. This blunting of HPA axis reactivity was associated with a decrease in depression-like and anxiety-like behaviors. Exogenous CORT was sufficient to increase anxiety-like and depressionlike behaviors in Gabrd/Crh mice. Together, these results show the importance of the GABA(A)R delta subunit in the regulation of CRH neurons, and thus the HPA axis, and demonstrate that dysregulation of CRH neurons alters stress-related behaviors. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据