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      Loss of Gabrd in CRH neurons blunts the corticosterone response to stress and diminishes stress-related behaviors.

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          Abstract

          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 GABAAR δ 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 GABAAR δ 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 GABAAR δ 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 depression-like behaviors in Gabrd/Crh mice. Together, these results show the importance of the GABAAR δ subunit in the regulation of CRH neurons, and thus the HPA axis, and demonstrate that dysregulation of CRH neurons alters stress-related behaviors.

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          Author and article information

          Journal
          Psychoneuroendocrinology
          Psychoneuroendocrinology
          1873-3360
          0306-4530
          Mar 2014
          : 41
          Affiliations
          [1 ] Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, United States.
          [2 ] Department of Neuroscience, Tufts University School of Medicine, Boston, MA, United States.
          [3 ] Department of Neuroscience, Tufts University School of Medicine, Boston, MA, United States. Electronic address: jamie.maguire@tufts.edu.
          Article
          S0306-4530(13)00447-2 NIHMS552189
          10.1016/j.psyneuen.2013.12.011
          3947777
          24495609
          Copyright © 2013 Elsevier Ltd. All rights reserved.

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