α 2A -adrenergic receptor activation decreases parabrachial nucleus excitatory drive onto BNST CRF neurons and reduces their activity in Vivo

Tracy L. Fetterly, Aakash Basu, Brett P. Nabit, Elias Awad, Kellie M. Williford, Samuel W. Centanni, Robert T. Matthews, Yuval Silberman, Danny G. Winder

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Stress contributes to numerous psychiatric disorders. Corticotropin releasing factor (CRF) signaling and CRF neurons in the bed nucleus of the stria terminalis (BNST) drive negative affective behaviors, thus agents that decrease activity of these cells may be of therapeutic interest. Here, we show that acute restraint stress increases cFos expression in CRF neurons in the mouse dorsal BNST, consistent with a role for these neurons in stress-related behaviors. We find that activation of α 2A -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 α 2A -ARs specifically reduce excitatory drive from parabrachial nucleus (PBN) afferents onto CRF neurons. Given that the α 2A -AR is a G i -linked GPCR, we assessed the impact of activating the G i -coupled DREADD hM4Di in the PBN on restraint stress regulation of BNST CRF neurons. CNO activation of PBN hM4Di reduced stress-induced Fos in BNST Crh neurons. Further, using Prkcd as an additional marker of BNST neuronal identity, we uncovered a female-specific upregulation of the coexpression of Prkcd/Crh in BNST neurons following stress, which was prevented by ovariectomy. These findings show that stress activates BNST CRF neurons, and that α 2A -AR activation suppresses the in vivo activity of these cells, at least in part by suppressing excitatory drive from PBN inputs onto CRF neurons.

Original languageEnglish (US)
Pages (from-to)472-484
Number of pages13
JournalJournal of Neuroscience
Volume39
Issue number3
DOIs
StatePublished - Jan 16 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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