# An optogenetic approach to airway research

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $231,000

## Abstract

We have recently shown that there are substantial changes in airway innervation in patients with severe
asthma. In both these patients and in several mouse models of asthma, inflammatory changes lead to
significant changes in nerve structure and phenotype.
 We hypothesize that structural and phenotypic changes in airway innervation are central to
asthma pathophysiology. In order to characterize these changes functionally, we propose to develop an
optogenetic approach to stimulating or silencing two populations of airway neurons: 1) cholinergic efferents,
and 2) substance P containing afferents. We propose two specific aims:
SPECIFIC AIM #1: We will apply optogenetic methods to stimulate or silence specific populations of
airway neurons. We will express the light sensitive cation channel channelrhodopsin (ChR2) in two
populations of neurons, by driving expression of the ChR2 with the promoters for choline acetyltransferase
(for cholinergic parasympathetic neurons), and for substance P (Tac1, the promoter for the preprotachykinin
gene, for substance P containing sensory neurons). This will allow us to activate these neurons selectively,
and study the effects on airway function. Conversely, we will express halorhodopsin (a light-sensitive anion
channel that hyperpolarized cells) in the same populations of neurons, allowing us to silence these neurons
SPECIFIC AIM #2: We will apply these optogenetic methods to defining functional changes in the
sensory and parasympathetic control of airway smooth muscle in a mouse model of eosinophilic
asthma, using transgenic mice expressing IL5 in airway epithelial cells (causing intense airway
eosinophilia and hyperinnervation). These mice display markedly increased reflex bronchoconstriction in
response to inhaled serotonin. As both afferent (sensory) and efferent (parasympathetic) nerves are
abnormal in asthma and reflex bronchoconstriction is increased in these animals, we will test the effects of
selectively stimulating or silencing cholinergic neurons, and of stimulating or silencing substance P
containing sensory neurons.
At the completion of this project, we will have established a new method for investigating the neural control of
the airways, and for defining the role of subpopulations of neurons as well as their changes in models of
airway disease. Going forward, we will apply this method, as well as optogenetic stimulation or silencing of
other populations of neurons, to the study of other models of asthma, including viral infections, antigen
challenge, and ozone inhalation.

## Key facts

- **NIH application ID:** 9997568
- **Project number:** 1R21AI152498-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** David B Jacoby
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-03-09 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997568

## Citation

> US National Institutes of Health, RePORTER application 9997568, An optogenetic approach to airway research (1R21AI152498-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997568. Licensed CC0.

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