# Leveraging vagal oxytocin receptors to understand cardiometabolic interoception

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2022 · $588,044

## Abstract

Project Summary
Oxytocin is a hypothalamus-derived neuropeptide well-known for shaping the perception of social stimuli and
recognized for its actions at the oxytocin receptor (Oxtr) within the brain, where it orchestrates emotional and
homeostatic responses to social stimuli. As a result, oxytocin is considered a mediator of exteroception and is in
clinical trials for diseases ranging from autism to obesity. While less-studied, Oxtr(s) are also expressed in the
peripheral nervous system, and we propose that investigation of these Oxtr(s) is critical to unraveling the
intricacies of interoception. Our preliminary studies in mice revealed that within the nodose ganglia (NDG),
Oxtr(s) demarcate specific neurons innervating the aortic arch, stomach and duodenum. Fascinatingly,
excitation of Oxtr-expressing neurons in the NDG (referred to as NDGOxtr) elicits a robust cardiometabolic
response typified by lowered blood pressure and food intake. Our interpretation of these results is that NDGOxtr
can be studied to understand how signals from the vasculature or gastrointestinal (GI) tract are relayed to the
brain and could lead to novel insights for developing mind-body interventions to alleviate diseases that impact
multiple organs in the cardiometabolic axis. In human fMRI studies, perturbations in blood pressure or GI
distension change the activity of the prefrontal cortex (PFC), and intriguingly, we found that excitation of NDGOxtr
also alters the activity of a subset of PFC neurons. These results suggest that NDGOxtr influence cortical neurons
encoding interoception of the vasculature or GI tract to orient behavior toward restoring homeostasis. Finally,
the presence of the Oxtr within the NDG, in conjunction with reports that oxytocin depolarizes NDG neurons,
suggests that Oxtr(s) promote excitation of vagal afferents to increase the sensitivity by which the vasculature
or GI tract are perceived. These observations have led to the hypothesis that distinct NDGOxtr shape
interoception through separate neural circuits that relay signals from the vasculature or GI tract to the
PFC. We further hypothesize that oxytocin enhances this interoception by increasing the sensitivity of
vagal afferents to cardiometabolic alterations. We will pursue the following Specific Aims. Aim 1 uses
neuroanatomical tracing, intravital imaging of NDG and in vivo optogenetics with physiological and behavioral
recordings to determine whether separate populations of NDGOxtr respond to stimulation of the vasculature or GI
tract to elicit distinct compensatory responses. Aim 2 uses intravital imaging of the PFC and in vivo optogenetics
with physiological and behavioral recordings to evaluate whether NDGOxtr innervating the vasculature or GI tract
affect the excitation-inhibition balance of PFC neurons to orient behavior toward rectification of homeostatic
need. Aim 3 uses tissue specific gene deletion, intravital imaging and pharmacology to investigate how Oxtr(s)
expressed by th...

## Key facts

- **NIH application ID:** 10698525
- **Project number:** 1R56AT012142-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** CHARLES J FRAZIER
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $588,044
- **Award type:** 1
- **Project period:** 2022-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698525

## Citation

> US National Institutes of Health, RePORTER application 10698525, Leveraging vagal oxytocin receptors to understand cardiometabolic interoception (1R56AT012142-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10698525. Licensed CC0.

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