α2A-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis

Stephanie A. Flavin, Robert T. Matthews, Qin Wang, E. Chris Muly, Danny G. Winder

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α2A-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α2A-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α2A-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α2A-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α2A-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs.

Original languageEnglish (US)
Pages (from-to)9319-9331
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number28
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Adrenergic receptors
  • Bed nucleus of the stria terminalis
  • Excitatory transmission
  • Extended amygdala
  • Norephinephrine
  • Optogenetics

ASJC Scopus subject areas

  • General Neuroscience

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