# A molecular and functional dissection of the vagal heart-to-brain physiological circuits

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $418,750

## Abstract

Project Summary/Abstract
The heart is extensively innervated by the vagus nerve, and numerous vital heart-derived cues are
actively sensed, including pressure fluctuations associated with every heartbeat, secreted peptides and
signaling molecules, and pathological changes such as tissue damage, ischemia, and inflammation.
Appropriate detection of heart signals is a first and key process in cardiovascular reflexes; however,
the mechanisms by which the brain receives messages from the heart via the vagus nerve are still
mysterious, and many essential questions about this heart-to-brain interface remain to be answered.
Are different heart signals detected by different sensory neurons? What are the anatomical and
molecular basis for sensing diverse cardiac inputs? How do distinct heart changes differentially regulate
cardiovascular physiology? Here, we propose to bring knowledge and innovative technologies in
neuroscience, physiology, genetics, and computational biology to this important interdisciplinary area
to better understand the neural mechanisms that control cardiovascular functions. In preliminary studies,
we identified two genetically distinct vagal sensory neurons subtypes marked by Npy2r and Piezo2 that
both innervate the heart. Vagal Npy2r and Piezo2 neurons have fundamentally different gene
expression patterns, electrical properties, and anatomical features and physiological roles in visceral
organs other than the heart, suggesting they represent two distinct heart-to-brain pathways. Previously,
we have developed a number of novel molecular and genetic techniques in the vagus nerve to enable
cell-type specific studies for anatomy, neuronal activity, and physiological function of genetically defined
vagal neuron populations. Here we will employ these powerful tools to determine, through three specific
aims, whether vagal Npy2r and Piezo2 heart-to-brain neurons display distinct anatomical architectures,
respond to different cardiac inputs, and differentially regulate a diversity of cardiovascular functions.
We expect that studies proposed here will reveal many important details for two distinct vagal heart-to-
brain circuits. We believe the proposed project will provide not only a critical foundation for delineating
the underlying sensory mechanisms but also genetic access for charting distinct heart-to-brain neural
circuits and precise modulation of cardiovascular functions. A molecular and functional dissection of
the heart-to-brain axis will open up new vistas in this important area of neural control of the
cardiovascular system and may bring novel concepts and therapeutic targets into the field of
cardiovascular disease intervention and prevention.

## Key facts

- **NIH application ID:** 10526423
- **Project number:** 5R01HL150449-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** RUI CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2019-12-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526423

## Citation

> US National Institutes of Health, RePORTER application 10526423, A molecular and functional dissection of the vagal heart-to-brain physiological circuits (5R01HL150449-04). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10526423. Licensed CC0.

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