# Interactions of the Noradrenergic and Serotonergic Systems in Autoresuscitation

> **NIH NIH F32** · BAYLOR COLLEGE OF MEDICINE · 2024 · $84,364

## Abstract

Project Summary/ Abstract
The noradrenergic (NA) and serotonergic (5-HT) networks of the brainstem are highly regulated and necessary
components of the respiratory homeostatic network. Dysfunction of these systems has been linked to many
congenital respiratory disorders including Sudden Infant Death Syndrome (SIDS). SIDS is a leading cause of
neonate death and is thought to occur, in part, by the failure of the neonate autoresuscitation reflex. Previous
data have informed our understanding of how these systems modulate protective respiratory responses to life
threatening challenges independently, but limited information is available on the potential interplay between
these two key systems while previous studies lack a more finessed manipulation provided by our methodology.
In the following aims, I will test the hypothesis that the 5-HT and NA systems are integrally linked in regulating
the autoresuscitation reflex and that different combinations of 5-HT and NA perturbation and stimulation will
result in additive positive and negative outcomes in autoresuscitation. Aim 1. Determine the separate and
combined functional and cellular effects of serotonergic activation and noradrenergic inhibition on the
autoresuscitation reflex and respiratory network dynamics in response to hypercapnic anoxia. Aim 2. Determine
the effect of serotonergic inhibition and noradrenergic activation on the autoresuscitation reflex. Aim 3.
Determine the effect of serotonergic inhibition and noradrenergic inhibition or serotonergic activation and
noradrenergic activation on the autoresuscitation reflex. To test these aims, I will utilize compounded
recombinase and effector lines to access and manipulate the activity of the 5-HT and NA systems. For example,
the Pet1::Cre; F_hM4D line bred to a DBH_FLPo; P_hM3D line will produce mice that, upon clozapine-N-oxide
(CNO) application, will concurrently excite the 5-HT system (Pet1::Cre + P_hM3D) while inhibiting the NA system
(DBH_FLPo + F_hM4D). For functional characterizations, the mice will be challenged with repeated bouts of
hypercapnic anoxia to test their autoresuscitation reflex. For network activity characterization, cFos staining will
be carried out on brainstem tissue in mice that have been challenged with sublethal hypercapnic anoxic
exposures after excitation or inhibition of the 5-HT or NA systems. Understanding if these systems are
independently regulating autoresuscitation will provide valuable information for future therapeutic investigations.
This study will progress the field by expanding our understanding of interplay between the 5-HT and NA systems
in health and disease as well as informing on the use of intricate genetic manipulations in the study of these two
key respiratory systems. This work will significantly advance our understanding of the neural networks involved
in respiratory regulation and disease. The training plan and environment that accompany this proposal will
provide a solid foundation for a t...

## Key facts

- **NIH application ID:** 10899753
- **Project number:** 5F32HL160073-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Savannah J Lusk
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $84,364
- **Award type:** 5
- **Project period:** 2022-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899753

## Citation

> US National Institutes of Health, RePORTER application 10899753, Interactions of the Noradrenergic and Serotonergic Systems in Autoresuscitation (5F32HL160073-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899753. Licensed CC0.

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