# Chemogenetic dissection of noradrenergic system and sleep apnea.

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2020 · $173,912

## Abstract

Abstract
 Obstructive sleep apnea (OSA) is a growing sleep-related breathing disorder affecting up to 10% of the
adult population compared to 2-4% in 1993. OSA patients undergo recurrent upper airway collapse due to
suppression of upper airway dilator muscle activity during sleep, and thus suffer from repeated hypoxia,
frequent stressful arousals sleep deprivation. OSA has a major clinical impact due to its cardiovascular,
metabolic and neurocognitive sequelae.
 Brainstem noradrenergic (NA) system plays a critical role in the pathology of OSA by maintaining the
tonus of upper airway (UA) muscles that keep airway open. The NA system is also a major contributor to the
neuronal mechanisms that lead to a loss of the UA muscle tone during rapid-eye-movement (REM) sleep.
However, there is limited information regarding functional relationship between particular groups of NA neurons
and UA muscles. Most importantly, there was no attempt to assess relative contribution of each of the
brainstem NA group in depression of UA muscle activity during NREM and REM sleep.
 In the proposed research project, we will use a combination of techniques: chronic intermittent hypoxia
(CIH), a major pathogenic factor in OSA, and a novel molecular-genetic technology that will allow a cell-type-
specific activation or inhibition of NA neurons in each of the brainstem groups (A1, A2, A5, Locus Coeruleus,
SubC, and A7) while recording activity of the genioglossus (GG) muscles during sleep-wake cycles in behaving
DBH-Cre transgenic mice. We will 1) determine the functional relationship between activity of these NA groups
and GG muscle activity and effect of CIH on this relationship; 2) quantify the relative contribution of each of the
NA neuronal groups to the depression of GG activity during natural NREM and REM sleep in CIH- and sham-
treated mice; 3) identify the pattern of efferent connections of each of the NA groups to and within the
hypoglossal nucleus, a major nucleus innervating UA muscles including the GG muscle, and to other medullary
sites important for the control of upper airway muscle tone; and 4) determine the magnitude of CIH-induced
sprouting of axonal terminals within the hypoglossal nucleus that originate from different NA nuclei.
 The proposed work will rank the brainstem NA neuronal groups according to their involvement in the
control of UA muscles in CIH and control mice. Importantly, it will quantitatively characterize the contribution of
each of the NA group to depression of GG muscle activity during NREM and REM sleep in mice subjected to
CIH or sham exposure. Therefore, results of this study will fill a major gap in our understanding of the
underlying mechanisms of OSA pathogenesis and may help in designing pharmacological or genetic
treatments to prevent OSA.

## Key facts

- **NIH application ID:** 10203076
- **Project number:** 7R01HL133847-05
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Victor Borisovich Fenik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $173,912
- **Award type:** 7
- **Project period:** 2020-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203076

## Citation

> US National Institutes of Health, RePORTER application 10203076, Chemogenetic dissection of noradrenergic system and sleep apnea. (7R01HL133847-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10203076. Licensed CC0.

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