# Neurobiology of Intrinsic Primary Afferent Neurons

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $317,957

## Abstract

Project Summary / Abstract
The gastrointestinal (GI) tract is the only organ system that is capable of intrinsic neural reflexes. These are
initiated by a unique neuron type called intrinsic primary afferent neurons (IPANs). IPANs are key to
orchestrating neural reflexes that allow efficient processing of meals for nutrient uptake by rapidly adapting to
changing luminal content to alter vascular, secretory and motor function. In the guinea pig, IPANs use multiple
mechanisms of neuroplasticity to adapt to inflammatory, hormonal and neural stimuli. From these studies it is
clear that IPAN neuroplasticity mediates digestive disease. Even though the mouse has become the vertebrate
animal model of choice for digestive disease, murine IPANs have lacked consensus markers making precise
studies of mouse IPANs inconceivable. These issues are now resolved by our recent transcriptome and
morphological analysis of the ENS, which challenges the dogma that IPANs are a single class of neuron, and
suggest that rather there are four classes of IPANs. In combination with recent advances in morphological (i.e.
tissue clearing) and physiological approaches (i.e. genetically-encoded markers and activity indicators) we are
now able to study mouse IPANs in a relatively high throughput manner. The objective of this proposal is to test
the overall hypothesis that different classes of IPANs possess morphologies and physiology that uniquely
contribute to intestinal function. This hypothesis will be tested in a series of experiments designed to address
three specific aims: Specific Aim 1: determine the structure of receptive fields and connectivity of murine
IPANs; Specific Aim 2: determine responses of murine IPANs to mechanical and chemical stimuli; Specific Aim
3: determine the role of IPANs in gastrointestinal physiology. Collectively, these studies address a critical gap
in our knowledge on the basic neural control of gut functions. Deciphering sensory capabilities and functional
responses of molecularly defined IPANs are likely to pave the way for future improvements in diagnostic and
therapeutic strategies of digestive disease.

## Key facts

- **NIH application ID:** 10680037
- **Project number:** 3R01DK129315-02S1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** David R. Linden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $317,957
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10680037

## Citation

> US National Institutes of Health, RePORTER application 10680037, Neurobiology of Intrinsic Primary Afferent Neurons (3R01DK129315-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10680037. Licensed CC0.

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