# Elucidating Central Neural Mechanisms in an Apnea Model

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,036

## Abstract

Project summary:
Central apnea plays a predominant role in death in a range of disorders including congestive heart failure, opioid
addiction, sudden infant death syndrome, and epilepsy; however, robust preclinical animal models to study
central apnea and the underlying neural circuitry are lacking. We found that upon exposure to a synthetic
predator odor, mice exhibit a unique breathing pattern consisting of increased apnea frequency. This proposal
will establish this novel apnea model through predator odor exposure and uncover a neural circuit for central
apnea generation in mice. Aim 1 will rigorously determine how the stimulus intensity (i.e., dose of the predator
odor) affects both central apnea and behavioral output such as freezing. In addition to olfactory activation,
odorants activate the somatosensory system in a concentration dependent manner which may initiate protective
apnea; thus, we will probe the olfactory requirement for predator odor apnea induction. We will then evaluate
whether an odor with similar aversive quality, that fails to induce freezing, also induces apnea in a concentration-
dependent manner. These fundamental experiments will further develop our understanding of how apnea relates
to various stimulus qualities of predator odor. Furthermore, existing literature in animal models focuses on the
brainstem central pattern generator that coordinates the motor output for breathing, but currently research lacks
investigation of top-down modulation of breathing from circuits involved in behavior. Clinical data consistently
show that the amygdala drives apnea in humans and likely contributes to sudden death in epilepsy in temporal
seizures; however, the amygdala’s role in apnea is unknown in mice. The central amygdala is involved in
behavioral responses to fearful stimuli such as predator odor and sends direct projections to ponto-medullary
respiratory regions. Aim 2 will isolate the functional role of neurons in the central amygdala that are activated
and genetically tagged by predator odor to determine their involvement in apnea generation. Given the
advantages of a genetically tractable mouse model, we will elaborate this mechanism by identifying the
predominant cell type(s) responsible in the central amygdala and their downstream targets. Completion of these
aims will enrich our understanding of apnea induced by predator odor while providing a novel limbic mechanism
for a central apnea model in mice.

## Key facts

- **NIH application ID:** 10232885
- **Project number:** 1F31MH124372-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Emma Catherine Janke
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232885

## Citation

> US National Institutes of Health, RePORTER application 10232885, Elucidating Central Neural Mechanisms in an Apnea Model (1F31MH124372-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10232885. Licensed CC0.

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