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Title page for ETD etd-09162018-191654


Type of Document Dissertation
Author Fetterly, Tracy Lynne
URN etd-09162018-191654
Title Dissecting the Stress Recruitment of BNST CRF Neurons: Regulation of Glutamatergic Inputs via Gi-coupled GPCR Signaling
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Sachin Patel Committee Chair
Brad A. Grueter Committee Member
Danny G. Winder Committee Member
David H. Wasserman Committee Member
Keywords
  • bed nucleus
  • stress
  • CRF
  • norepinephrine
Date of Defense 2018-09-13
Availability restricted
Abstract
Stress contributes to numerous psychiatric disorders. CRF signaling in the bed nucleus of the stria terminalis (BNST) drives negative affective behaviors, thus agents that decrease activity of these cells may be of therapeutic interest. We show that acute restraint stress increases cFos expression in CRF neurons in the BNST, consistent with a role for these neurons in stress-related behaviors. We find that activation of α2A-adrenergic receptors (ARs) by the agonist guanfacine reduced cFos expression in these neurons both in stressed and unstressed conditions. Further, we find that α- and β-ARs differentially regulate excitatory drive onto these neurons. Pharmacological and channelrhodopsin-assisted mapping experiments suggest that α2A-ARs specifically reduce excitatory drive from parabrachial nucleus (PBN) afferents onto CRF neurons. We assessed the impact of activating the Gi-coupled DREADD hM4Di in the PBN on restraint stress regulation of BNST CRF neurons. CNO administration reduced stress-induced Fos only in female BNST Crh neurons. Further, utilizing Prkcd as an additional marker of BNST neuronal identity, we uncovered a female-specific upregulation of the co-expression of Prkcd/Crh in BNST neurons following stress, which was prevented by ovariectomy. These findings show that stress activates BNST CRF neurons, and that α2A-AR activation suppresses the in vivo activity of these cells, at least in part by suppressing excitatory drive from PBN inputs onto CRF neurons.
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