Oxytocin Receptor Expression and Activation in Parasympathetic Brainstem Cardiac Vagal Neurons

Area of Science:

• Neuroscience
• Cardiology
• Endocrinology

Background:

• Autonomic imbalance, marked by reduced parasympathetic cardiac vagal neuron (CVN) activity, is common in cardiorespiratory diseases.
• Oxytocin (OXT) neurons in the hypothalamus form an excitatory pathway to CVNs, suggesting OXT as a potential therapeutic agent.
• Intranasal OXT has shown promise in improving autonomic balance and reducing symptoms in obstructive sleep apnea patients, but mechanisms are unclear.

Purpose of the Study:

• To investigate the localization of oxytocin receptors (OXTRs) in cardiac vagal neurons (CVNs) within the mouse nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX).
• To determine the effect of OXT on the activity of CVNs in the NA and DMNX.
• To explore the potential of targeting OXTR-expressing CVNs for therapeutic interventions.

Main Methods:

• Characterization of OXTR colocalization in CVNs and non-CVN cholinergic neurons in male and female mouse NA and DMNX.
• Electrophysiological recording to assess the effect of OXT on CVN firing rates.
• Selective chemogenetic activation of OXTR+ CVNs in the DMNX using DREADDs.

Main Results:

• OXTRs were highly expressed in CVNs within the DMNX, but not in the NA.
• OXT selectively increased the firing rate of DMNX CVNs, with no effect on NA CVNs.
• Chemogenetic excitation of OXTR+ DMNX CVNs induced rapid and sustained bradycardia.

Conclusions:

• Cardiac vagal neurons in the DMNX express functional oxytocin receptors.
• Activation of DMNX CVNs expressing OXTR with oxytocin offers a potential therapeutic strategy for restoring autonomic balance in cardiorespiratory disorders.
• This study identifies a specific neural pathway for OXT's effects on cardiac autonomic control.