Obstructive sleep apnea (OSA) is a sleep disorder characterized by repeated episodes of airway obstructions resulting in recurrent decreases in blood O 2 , also known as chronic intermittent hypoxia (CIH). A major cause of OSA is insufficient neural control of airway muscles, primarily in the tongue, leading to a failure in maintaining a patent airway. The majority of innervation to the tongue is mediated by hypoglossal motor neurons of cranial nerve XII (CN XII) in the hypoglossal motor nucleus and is driven by the rhythmic activity of the PreBötzinger Complex (preBötC). There is known serotonergic, noradrenergic, and cholinergic involvement in inspiratory rhythm, however cholinergic modulation, mediated by nicotinic and muscarinic acetylcholine receptors, is less well understood. This study examines the effects of CIH on cholinergic modulation of inspiratory activity. We hypothesize that muscarinic excitability at hypoglossal motor neurons will be enhanced in response to CIH. Rhythmic medullary slices were obtained from neonatal mice ranging from postnatal ages 1 through 14 days. Relative changes in peak amplitude and burst frequency were measured from CN XII nerve rootlets via bath application of acetylcholine (1 μM, 10 μM, 100 μM, 200μM) and muscarine (1 μM, 10 μM). In P3-4 (n=9), preliminary data showed acetylcholine decreased burst frequency by 1.67% ±9.25%, 5.83% ±16.79%, 7.79% ±14.66%, and 8.49% ±10.00% for 1, 10, 100, and 200 μM doses, respectively, compared to baseline. Peak burst amplitude increased by 1.45% ±15.63%, 12.56% ±24.92%, 14.02% ±22.91%, and 14.77 ±29.15% for the same doses. In P7-8 (n=5), acetylcholine decreased burst frequency by 8.72% ±15.43% at 1 μM, increased burst frequency by 7.02% ±26.84% at 10 μM, and decreased burst frequency by 16.25% ±13.42% and 16.84% ±12.36% for 100 μM and 200 μM doses, respectively. Peak burst amplitude decreased by 16.34% ±9.89%, 0.50% ±14.09%, 1.27% ±29.94%, and 4.06% ±47% for the same doses. In P3-4 (n=7), muscarine decreased burst frequency by 14.89% ±12.15% and 25.37% ±14.87% for 1 μM and 10 μM doses, respectively, compared to baseline. Peak burst amplitude increased by 50.71% ±33.50% and 56% ±23.99% for the same doses. In P7-8 (n=4), muscarine decreased burst frequency by 33.51% ±18.69% and 43.42% ±25.94% under 1 μM and 10 μM doses, respectively, compared to baseline. Peak burst amplitude increased by 16.83% ±29.14% and 29.77% ±63.36% for the same doses. Muscarine likely had a larger effect on burst frequency and amplitude due to endogenous acetylcholinesterase decreasing the half-life of acetylcholine. Future work will assess the effect of physostigmine on cholinergic modulation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Sinitsyn et al. (Fri,) studied this question.