2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis
Year: 2014
Type: article
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 α(2A)-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 α(2A)-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 α(2A)-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 α(2A)-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 α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs.
Source: Journal of Neuroscience
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: Vanderbilt University, National Institutes of Health, School of Medicine, Vanderbilt University, National Institute on Drug Abuse, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1149166549, G2940777275, G35732448, G3722609264, G3744589275, Medical Scientist Training Program, G3865556588, G3989539122, Vanderbilt Mouse Metabolic Phenotyping Center, Input-specific Regulation of Transmission by Alpha2A Adrenergic Receptors, G4320917349, G4513176822, G5105175959, G5853943267, G7220527126, Support of Yerkes National Primate Research Center, G9000002043, G9000041349, G9000060478, G9000081609, G9000106052, G9000159340, Molecular and Cellular Basis for Digestive Diseases, Cancer Center Support Grant, Vanderbilt Diabetes Research Center, Core Grant in Vision Research
OpenAlex ID: W2075804464