# Homeostatic Plasticity of the Respiratory Rhythm Generating Network

> **NIH NIH K99** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $104,687

## Abstract

PROJECT SUMMARY
This career development award will allow the Candidate, Dr. Nathan Baertsch, to establish an independent
research career focused on unravelling how the brain adapts to maintain breathing during disease. The
training plan outlined in this award combined with the Candidate’s background in motor plasticity, respiratory
physiology and rhythm generation make him ideally suited to successfully follow this career development path.
The breathing rhythm is generated by periodic synchronization of excitatory interneurons in the preBötzinger
Complex (preBötC). The search for the essential rhythmogenic mechanism has been a central question in the
control of breathing field for over two decades. Although this search has revealed many important discoveries,
it has overlooked perhaps one of the most fundamental characteristics of the network – its ability to adapt. The
amount of synchronization among preBötC neurons is not fixed, but depends on a dynamic interplay between
excitatory and inhibitory connections, and the intrinsic membrane properties of preBötC neurons. How this life-
sustaining neural network regulates this precise balance of synaptic and intrinsic properties to ensure
breathing remains robust is not well understood. Based on preliminary data, we hypothesize that the
distribution of the network generating inspiration is adaptable, and the balance between synaptic excitation,
inhibition, and intrinsic bursting properties can be homeostatically tuned to compensate for chronic
perturbations that threaten rhythmogenesis and breathing. This project will build on the candidate’s prior
training in electrophysiology, pharmacology, and optogenetics by introducing state-of-the-art chemogenetic,
imaging, and molecular techniques. Combining these strategies will allow the Candidate to use a multi-level
approach to characterize changes in the distribution of inspiratory activity (Aim1) and identify changes in
synaptic and intrinsic properties (Aim2) in the preBötC following chronic disruptions in neuronal activity. These
in vitro experiments using a novel brainstem slice preparation will be complemented with in vivo experiments to
explore how breathing adapts to chronic suppression of preBötC activity in the intact animal (Aim3). To help
the Candidate achieve the research and career development goals of this proposal, he will receive strong
mentorship from Dr. Nino Ramirez, a leader in respiratory rhythm generation with a successful mentoring track-
record. The Candidate will also receive research and career development support from an advisory committee
of established professors and former K-awardees that have transitioned to independence. These PIs all work
closely with the Candidate and are experts in the chemogenetic, imaging, and molecular techniques that will be
training components of this proposal. With full institutional support and the additional training, mentorship, and
experience that this K-award will provide, the Candidate will b...

## Key facts

- **NIH application ID:** 9843742
- **Project number:** 5K99HL145004-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Nathan Andrew Baertsch
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $104,687
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843742

## Citation

> US National Institutes of Health, RePORTER application 9843742, Homeostatic Plasticity of the Respiratory Rhythm Generating Network (5K99HL145004-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843742. Licensed CC0.

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