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

Abstract

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 hATcre/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 PiCo's 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 PiCo's role in swallow and laryngeal coordination will aid in understanding discoordination in breathing and neurological diseases.

Chronic Intermittent Hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

“…Each dot represents the average duration per mouse. The gold dots represent mice exposed to CIH and the black dots are in control mice exposed to room air taken from Figure 3A in (A. D. Huff et al, 2023).…”

“…Recently published studies have demonstrated that PiCo acts as a gate for swallow and laryngeal postinspiratory behaviors and aids in the proper coordination and timing for swallow and breathing (Ain Summan Toor et al, 2019; A. D. Huff et al, 2023). In the present study we explored the effects of CIH on PiCo and its role in coordinating swallowing and breathing in order to understand how OSA and other disorders associated with intermittent hypoxia (e.g.…”

“…epilepsy, Rett Syndrome) lead to dysphagia. Building on the experiments preformed in our control cohort (A. D. Huff et al, 2023) we studied the impact of CIH using an established mouse model for OSA (Garcia et al, 2017; Garcia et al, 2016; A. Huff et al, 2022; Peng & Prabhakar, 2004; Peng et al, 2021).…”

“…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 (A. D. Huff et al, 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT).…”

The breath shape controls intonation of mouse vocalizations

“…The iRO is molecularly defined in the neonate by the co-expression of Preproenkephalin (Penk) and Vesicular glutamate transporter 2 (Vglut2) and is anatomically localized to the medullary ventral intermediate Reticular Formation (iRT) directly medial to the compact nucleus ambiguus 17,19 (Wei et al, 2022). This general region has been dubbed the Post inspiratory Complex (PiCo) given its involvement in post-inspiration, including behaviors like swallowing (Anderson et al, 2014, Huff et al, 2023. We determined that the iRO molecular and anatomical features exists in adults in two ways.…”