# Efferent vagal modulation of neuropod cells in the small intestine

> **NIH NIH K01** · DUKE UNIVERSITY · 2022 · $120,270

## Abstract

ABSTRACT
 Functional gastrointestinal (GI) diseases are the most common diagnoses in gastroenterology. Such
disorders, like irritable bowel syndrome or functional dyspepsia, are recognized by altered GI sensitivity and
motility. Though the pathophysiology is complex, a conserved feature is the bidirectional alteration in brain-
gut signaling. Thus, these are classified as disorders of brain-gut interaction. While the vagus nerve is the
main brain-gut link, how the brain relays neural signals that modulate GI epithelial sensory function is
unknown. My long-term career goal is to document how neural circuits originating from the brain alter the
gut’s ability to sense nutrients. With the support of the NIH Mentored Research Scientist Development
Award — K01, the objective of this proposal is to delineate a brain-to-gut neural circuit that could be used to
alter sensory transduction at the gut epithelium. This will be accomplished in three aims:
 Aim 1. Determine the neurotransmitters and hormones released by intestinal sensory cells in
response to excitatory neurotransmitter stimulation. An in vitro organoid and sorted single cell assay will be
used to measure release in culture. This aim will demonstrate that an excitatory neurotransmitter can
stimulate vesicular release in enteroendocrine cells.
 Aim 2. Pair vagal stimulation with sensory epithelial cell calcium imaging and electrophysiology to
evaluate the functional connectivity of vagal neurons synapsing onto intestinal sensory cells. This aim will
demonstrate a functional connection where neurons increase the excitability of sensory cells in the proximal
small intestine.
 Aim 3. Utilize both retrograde (post- to pre-synapse) rabies virus and anterograde (pre- to post-
synapse) herpes simplex virus to trace a mono-synaptic connection between the brainstem and intestinal
sensory epithelial cells. This aim will establish an anatomical map for how the brainstem is connected to
neuropod cells.
 Identifying functional neural circuits connecting the brain and the gut will enable the understanding of
the mechanisms behind visceral hypersensitivity. Together with my mentoring team, we have designed this
project to provide me with the necessary research and professional training for me to excel as an
independent investigator in the field of sensory neurogastroenterology.

## Key facts

- **NIH application ID:** 10524799
- **Project number:** 1K01DK131403-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Melanie Maya Kaelberer
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $120,270
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524799

## Citation

> US National Institutes of Health, RePORTER application 10524799, Efferent vagal modulation of neuropod cells in the small intestine (1K01DK131403-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10524799. Licensed CC0.

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