Oxytocin Receptor Expression and Activation in Parasympathetic Brainstem Cardiac Vagal Neurons

Authors

Xin Wang, Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037.
Caitlin Ribeiro, Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037.
Anna Nilsson, Department of Cell and Molecular Biology, University of Hawaii, Honolulu, Hawaii 96813.
Joan B. Escobar, Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037.
Bridget R. Alber, Department of Biomedical Engineering, The George Washington University, Science & Engineering Hall, Washington, DC 20052.
John R. Bethea, Departments of Anatomy and Cell Biology, George Washington University, Washington, DC 20037.
Vsevolod Y. Polotsky, Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC 20037.
Matthew W. Kay, Department of Biomedical Engineering, The George Washington University, Science & Engineering Hall, Washington, DC 20052.
Kathryn Schunke, Department of Cell and Molecular Biology, University of Hawaii, Honolulu, Hawaii 96813.
David Mendelowitz, Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 dmendel@gwu.edu.

Document Type

Journal Article

Publication Date

8-1-2025

Journal

eNeuro

Volume

12

Issue

8

DOI

10.1523/ENEURO.0204-25.2025

Keywords

DMNX and NA; DREADDs; autonomic regulation; cardiac vagal neurons; chemogenetic; oxytocin receptors

Abstract

Autonomic imbalance-particularly reduced activity from brainstem parasympathetic cardiac vagal neurons (CVNs)-is a major characteristic of many cardiorespiratory diseases. Therapeutic approaches to selectively enhance CVN activity have been limited by the lack of defined, translationally relevant targets. Previous studies have identified an important excitatory synaptic pathway from oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus to brainstem CVNs, suggesting that OXT could provide a key selective excitation of CVNs. In clinical studies, intranasal OXT has been shown to increase parasympathetic cardiac activity, improve autonomic balance, and reduce obstructive event durations and oxygen desaturations in obstructive sleep apnea patients. However, the mechanisms by which activation of hypothalamic OXT neurons, or intranasal OXT, enhance brainstem parasympathetic cardiac activity remain unclear. CVNs are located in two cholinergic brainstem nuclei: nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). In this study, we characterize the colocalization of OXT receptors (OXTRs) in both CVNs and non-CVN cholinergic neurons in the male and female mouse NA and DMNX nuclei. We found that OXT receptors are highly expressed in CVNs in the DMNX, but not in the NA. OXT increases the firing of DMNX CVN, with no effect on NA CVNs. Selective chemogenetic excitation of OXTR+ CVNs in the DMNX-achieved by a combination of Cre- and flp-dependent DREADD expression-evoked a rapid and sustained bradycardia. These findings suggest that activation of DMNX CVNs expressing OXTR with oxytocin may represent a novel translational therapeutic target for restoring autonomic balance in cardiorespiratory disorders.

APA Citation

Wang, Xin; Ribeiro, Caitlin; Nilsson, Anna; Escobar, Joan B.; Alber, Bridget R.; Bethea, John R.; Polotsky, Vsevolod Y.; Kay, Matthew W.; Schunke, Kathryn; and Mendelowitz, David, "Oxytocin Receptor Expression and Activation in Parasympathetic Brainstem Cardiac Vagal Neurons" (2025). GW Authored Works. Paper 7730.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7730

Department

Pharmacology and Physiology