# Transcriptomic Identification of Vagal Motor Neurons That Differentially Regulate Gastric Function

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $38,810

## Abstract

Project Summary/Abstract
During normal digestion, the vagus nerve sends both relaxation signals to the stomach to accommodate
ingested food and contraction signals to triturate as well as passage food into the small intestines. These
opposing functions are mediated by the same brain region, the dorsal motor nucleus of the vagus (DMV), but
the mechanism by which vagal efferents deriving from the same anatomical brain structure exert different
effects is poorly understood. While previous studies have led to the well-accepted postulate that the DMV
contains separate functional units (i.e. labeled lines), these functional units have yet to be defined by gene
expression and consequently there are no known recombinase driver mice that allow for selective access to
the “labeled lines” of vagal motor communication. Thus, it is unknown how many DMV labeled lines exist and
what their respective roles are in digestion. By identifying genetically defined DMV subpopulations that control
gastric functions, we can test models for how the DMV subtypes exert different effects. One possibility is that
the DMV labeled lines exert different effects by engaging distinct postganglionic targets. In this model, the
DMV neurons that drive stomach contraction engage cholinergic enteric neurons and those that relax the
stomach activate enteric neurons that release nitric oxide. Evidence for this model, however, is inconclusive
due to the lack recombinase driver mice for genetic access to the DMV subtypes. To identify DMV subtypes by
their gene expression profiles, our lab has used single-nucleus RNA sequencing to transcriptionally profile, at
the single cell level, cholinergic (Chat+) parasympathetic preganglionic motor neurons in the DMV. The study
uncovered 9 subtypes of Chat+ DMV neurons and identified marker genes for genetic access. In Aim 1, we
will identify and obtain genetic access to the DMV subtypes that project to the stomach. We will assemble or
generate recombinase driver mice for each DMV subtype and use a recombinase-dependent adeno-
associated virus expressing an anterograde tracer to map axon projections. In Aim 2, we will characterize the
function of stomach-projecting DMV subtypes using optogenetics to manipulate the activity of each DMV
subtype and assays to measure physiological responses (e.g. gastric pressure, acid secretion, gastrin
secretion). In Aim 3, we will determine the downstream targets of the DMV subtypes that project to the
stomach using channelrhodopsin-2-assisted circuit mapping (CRACM). We will visualize cholinergic enteric
neurons using the existing Chat-GFP transgenic mouse line and nitrergic enteric neurons using Nos1-GFP
mice that we will generate. In summary, this proposal will parse out the DMV “labeled lines” that control gastric
function and provide recombinase driver mice for genetic access to each DMV subtype. Importantly, having
recombinase driver mice that provide selective access to each DMV “labeled line” will allow for un...

## Key facts

- **NIH application ID:** 9976721
- **Project number:** 1F31DK122620-01A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jenkang Tao
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,810
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976721

## Citation

> US National Institutes of Health, RePORTER application 9976721, Transcriptomic Identification of Vagal Motor Neurons That Differentially Regulate Gastric Function (1F31DK122620-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9976721. Licensed CC0.

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