# Role of serotonin in cardiorespiratory homeostasis in sleep and during severe hypoxia

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $381,823

## Abstract

The Sudden Infant Death Syndrome (SIDS) remains the leading cause of death between 1 month and
1 year of age. SIDS cases display more apnea as well as sleep abnormalities, including increased amounts of
active sleep (“AS”; i.e. rapid eye movement sleep), a state characterized by unstable breathing. Ultimately,
many SIDS cases die from cardiorespiratory collapse during an episode of severe hypoxia (failed
autoresuscitation). The underlying pathophysiology of these abnormalities is unclear.
 Most SIDS victims have defects in the brainstem 5-HT system, including reduced serotonin (5-HT) and
inhibitory 5-HT1A receptors. Neonatal rodents lacking central 5-HT have phenotypes reminiscent of SIDS,
including apnea and failed autoresuscitation. Our long-term goal is to illuminate the mechanisms by which 5-
HT prevents apnea during AS and facilitates autoresuscitation. The overarching hypothesis driving our
research is that brainstem 5-HT acts as a negative regulator of acetylcholine neurons in the pons and
GABAergic neurons in the medulla, leading to apnea during prolonged periods of AS and
compromised autoresuscitation, respectively.
 These hypotheses will be explored with the following Specific Aims:
Specific Aim 1: To determine the mechanisms by which a loss of central 5-HT leads to apnea during
prolonged periods of AS. Our working hypothesis is that signaling through 5-HT1A receptors located in the
LDT and/or PPT reduces drive to cholinoreceptive regions of the pons, including the Kolliker Fuse (KF)
nucleus, thereby terminating AS and mitigating apnea and respiratory instability in AS.
Specific Aim 2 (SA2): To determine mechanistically how a loss of central 5-HT compromises
autoresuscitation. Our working hypothesis is that signaling through 5-HT1A receptors helps to promote
autoresuscitation by reducing GABAergic drive within the ventrolateral medulla (VLM).
 Our research will reveal that 5-HT maintains cardiorespiratory homeostasis in infancy through
cholinergic and GABAergic pathways. It will be impactful as it will show how 5-HT signaling can 1) reduce the
chances of an infant becoming hypoxic during sleep, and 2) facilitate cardiorespiratory recovery when hypoxia
becomes severe. This mechanistic insight will be crucial for developing new pharmacological,
prophylactic strategies aimed at reducing SIDS incidence within at-risk populations.

## Key facts

- **NIH application ID:** 9869033
- **Project number:** 5R01HL136710-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Kevin James Cummings
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,823
- **Award type:** 5
- **Project period:** 2018-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869033

## Citation

> US National Institutes of Health, RePORTER application 9869033, Role of serotonin in cardiorespiratory homeostasis in sleep and during severe hypoxia (5R01HL136710-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869033. Licensed CC0.

---

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