# Functional mapping of peripheral and central circuits for airway protection and breathing

> **NIH NIH OT2** · UNIVERSITY OF FLORIDA · 2020 · $837,497

## Abstract

The peripheral and central elements of the respiratory control system are not “fixed,” but undergo sustained
(neuroplastic) circuit reorganization to optimize function. This system can selectively utilize unique afferent
modalities and brainstem neural pathways to elicit episodic, coordinated airway protective behaviors (e.g.
cough, laryngeal adduction). Neuroplasticity is induced and undermined by inflammation, transient afferent
feedback, or CNS injury. As a result, breathing responses and airway protective behaviors are altered in ways
that can be adaptive or maladaptive. Existing models of the brainstem network and sensory control system
regulating breathing and airway protection do not explain changes in responses caused by neuroplasticity in
sensory, central integrating and efferent motor elements of the control system. This knowledge gap concerning
peripheral and central circuit-based processes increases the risk of inappropriate depression in breathing or
airway protective mechanisms by the neuromodulatory approaches being investigated in the SPARC initiative.
In this project, our goal is to understand fundamental principles of modulation and plasticity in afferent
pathways, brain networks and efferent systems controlling breathing and airway defense. The proposed
research will advance our understanding of circuits underlying respiratory control, laying the foundation for
future neuromodulatory strategies to normalize lung function in vulnerable clinical populations. We have
assembled a multidisciplinary team to utilize cutting edge genetic, neuroanatomical, neurophysiological and
computational modeling approaches to interrogate sensory, central and motor pathways of the respiratory
control system. Complementary studies will be performed in human patient populations with various forms of
sensory or motor dysfunction, including those with laryngectomy, double lung transplants and unilateral vocal
fold paralysis. Through these parallel studies, we will reveal fundamental mechanisms of respiratory
neuroplasticity resulting from injury, disease and/or afferent activation. New knowledge from peripheral and
central circuits in animal models and humans with pathologies will be used to create an iterative, computational
neuromechanical model that incorporates key elements of neuroplasticity. This model will enable predictions
as we develop neuromodulatory approaches to inform novel treatments for respiratory dysfunction. The project
is separated into four encompassing aims. Aim 1: Identify neuroanatomical and functional plasticity of lung
sensory mechanisms that regulate brainstem pathways for airway protective reflexes. Aim 2: Identify short
time-scale and sustained, circuit-based plasticity in airway motor, brainstem and spinal respiratory motor
pathways induced by sensory feedback (airway and diaphragm) and/or injury/disease. Aim 3: Investigate key
features of neuroplasticity in human respiratory behaviors. Aim 4: Develop a neuromechanical com...

## Key facts

- **NIH application ID:** 10233687
- **Project number:** 3OT2OD023854-01S4
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** DONALD C BOLSER
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $837,497
- **Award type:** 3
- **Project period:** 2016-09-25 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233687

## Citation

> US National Institutes of Health, RePORTER application 10233687, Functional mapping of peripheral and central circuits for airway protection and breathing (3OT2OD023854-01S4). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233687. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*