Biology subjects

Huff, A. D.

Publications and source records attributed to Huff, A. D..

2 recordsLinked to original sources

bioRxiv2023

Chronic Intermittent Hypoxia reveals role of the Postinspiratory Complex in swallow pattern generation

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 preBotzinger 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.

neuroscience↗

bioRxiv2023

Postinspiratory complex acts as a gating mechanism regulating swallow-breathing coordination and other laryngeal behaviors

Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads to aspiration pneumonia, the leading cause of death in neurodegenerative diseases. Here we study the role of the postinspiratory complex, (PiCo) in coordinating breathing and swallowing. Using optogenetic approaches in freely breathing-anesthetized ChATcre, Vglut2cre and co-transmission of ChATcre/Vglut2FlpO mice reveals this small brainstem microcircuit acts as a central gating mechanism for airway protective behaviors. Activation of PiCo during inspiration or the beginning of postinspiration triggers swallow behavior, while there is a higher probability for stimulating laryngeal activation when activated further into expiration, suggesting PiCos role in swallow-breathing coordination. PiCo triggers consistent swallow behavior and preserves physiologic swallow motor sequence, while stimulates laryngeal activation variable to stimulation duration. Sufficient bilateral PiCo activation is necessary for gating function since activation of only a few PiCo neurons or unilateral activation leads to blurred behavioral response. Viral tracing experiments reveal projections from the caudal nucleus of the solitary tract (cNTS), the presumed swallow pattern generator (SPG), to PiCo and vice versa. However, PiCo does not directly connect to laryngeal muscles. Investigating PiCos role in swallow and laryngeal coordination will aid in understanding discoordination in breathing and neurological diseases.

neuroscience↗