Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production
Year: 2023
Type: article
Abstract: Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger Complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.
Source: eLife
DOI: 10.7554/elife.92175
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Characterizing the neural circuitry of postinspiratory behaviors and its coordination with breathing, G3877109183, Neuroglial interactions underlying the generation of the sigh, G5086831664, Integrative Consequences of Intermittent Hypoxia, G9000004418, G9000049369, Unraveling the dynamic mechanisms underlying opioid respiratory depression, Unraveling respiratory rhythm generation in medullary and supramedullary networks
OpenAlex ID: W4388540192