# Modeling the role of the NTS in the neurogenesis of airway defensive behaviors

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $743,416

## Abstract

PROJECT SUMMARY
Various neuromuscular diseases result in impaired cough (dystussia). Disorders of these airway protective
behaviors increase pulmonary infection due to aspiration, the leading cause of death in neuromuscular
disease. Mortality rates of aspiration pneumonia - present in over half of long-term care residents - can
approach 40%. Defense of the airway is achieved through coordination of multiple protective behaviors by
brain circuits that remain incompletely understood. A contemporary data-driven computational model
incorporating the brainstem network for breathing can rapidly reconfigure to produce the three phases a cough
motor pattern: inspiration, compression, and expulsion. However, critical elements of airway protection cannot
be explained. Based on motivating preliminary data and network simulations, we propose that a circuit in the
nucleus of the solitary tract (NTS) and dorsal medulla regulates phase timing and respiratory muscle drive
during paroxysmal coughs and exerts a command function over the brainstem respiratory control system to
coordinate coughing and breathing. The project has 3 Specific Aims: (1) Determine dynamic behavior-
dependent organization of NTS circuits during the expression of airway protective behaviors. (2) Determine
functional connectivity between NTS and VRC neurons during expression of coughing. (3) Reconstruct our
respiratory system model to incorporate regulation of both airway protective reflexes and breathing. Our unique
approach, building upon experimental interrogation of the NTS region, incorporates multi-array recording
technologies in an animal model system that generates defensive behaviors in response to physiologically
relevant airway perturbations. We anticipate that the project will lead to: a) a new, predictive model of airway
protection will be produced, b) we will understand functional relationships between conditionally active cells
and t-E NTS neurons in producing cough, and c) we will identify critical NTS to parafacial/VRC functional
relationships that regulate cough and breathing. This new knowledge will provide a critical step in
understanding the neurogenesis of cough and how this behavior is controlled to protect the airway.

## Key facts

- **NIH application ID:** 9849788
- **Project number:** 5R01HL131716-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** DONALD C BOLSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $743,416
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849788

## Citation

> US National Institutes of Health, RePORTER application 9849788, Modeling the role of the NTS in the neurogenesis of airway defensive behaviors (5R01HL131716-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9849788. Licensed CC0.

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