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Role of Postinspiratory Complex in Swallow Pattern Generation Revealed by Chronic Intermittent Hypoxia

Core Concepts
Chronic intermittent hypoxia disrupts swallow motor patterns through the Postinspiratory Complex.
Abstract: Chronic intermittent hypoxia (CIH) impacts swallow coordination through the Postinspiratory Complex (PiCo). Introduction: Obstructive sleep apnea (OSA) leads to dysphagia, with CIH affecting neuronal mechanisms in the ventral respiratory column. Swallow-Breathing Coordination: Swallow and breathing coordination relies on precise muscle activation, controlled by the caudal nucleus tractus solitaries (cNTS) and PiCo. Optogenetic Stimulation: Stimulation of PiCo neurons in CIH-exposed mice triggers variable swallow motor patterns and laryngeal activation. Swallow Probability: CIH alters the probability of triggering a swallow in different genetic mouse types. Laryngeal Activation: CIH affects laryngeal activation patterns, with burst submental activation observed. PiCo Phase-Dependent Response: Stimulation of PiCo triggers swallows or laryngeal activation in a phase-specific manner. Neuroanatomy: Post-hoc histological analysis confirms successful transfection of PiCo neurons in CIH-exposed mice. Conclusion: CIH disrupts the swallow motor pattern through PiCo, highlighting its role in dysphagia mechanisms.
CIH increases the gain of the carotid body response to hypoxia. Optogenetic stimulation of ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH triggers variable swallow motor patterns. Stimulation of ChATcre:Vglut2FlpO:ChR2 neurons in CIH-exposed mice triggers swallows in all 11 mice. Optogenetic stimulation of ChATcre:Ai32 and Vglut2:Ai32 neurons stimulates laryngeal activation in all CIH-exposed mice. CIH leads to disturbances in the generation of the swallow motor pattern activated by stimulating PiCo.
"PiCo is involved in swallow motor patterning and CIH disrupts connections between PiCo and the swallow pattern generator." "CIH leads to disturbances in the generation of the swallow motor pattern that is activated by stimulating PiCo."

Deeper Inquiries

How does the disruption of swallow motor patterns by CIH impact the risk of aspiration?

The disruption of swallow motor patterns by Chronic Intermittent Hypoxia (CIH) can significantly impact the risk of aspiration. Swallow motor patterns play a crucial role in ensuring the effective transport of food and liquid from the oral cavity into the esophagus, preventing aspiration into the airway. When the precise temporal sequences of swallows are altered, as seen in the study after CIH exposure, it can lead to variable swallow motor patterns. These abnormal patterns, such as simultaneous activation of submental and laryngeal muscles or tonic pre-swallow activity, can impair the proper clearance of the pharynx and increase the risk of aspiration. Aspiration, the entry of foreign materials into the lungs, can result in serious consequences such as aspiration pneumonia, a leading cause of morbidity and mortality in various respiratory and neurological disorders.

What implications do the findings have for understanding dysphagia in OSA and other disorders?

The findings from the study on the disruption of swallow motor patterns by CIH have significant implications for understanding dysphagia in Obstructive Sleep Apnea (OSA) and other related disorders. OSA is known to be associated with dysphagia, characterized by delayed swallow reflexes, disrupted swallow-breathing coordination, and alterations in the pharyngeal phase of swallow. The study's results suggest that CIH, a common feature of OSA, can lead to disturbances in the generation of swallow motor patterns, independent of swallow-breathing coordination. This indicates that dysphagia in OSA may involve central nervous dysfunction affecting the swallow pattern and laryngeal activation. Understanding these mechanisms is crucial for addressing dysphagia in OSA and other disorders associated with intermittent hypoxia, providing insights into potential therapeutic interventions to improve swallow function and reduce the risk of aspiration.

How can the role of PiCo in swallow coordination be further explored beyond the study's scope?

To further explore the role of the Postinspiratory Complex (PiCo) in swallow coordination beyond the study's scope, several avenues of research can be pursued: Neuronal Activity Studies: Conducting in-depth studies on the neuronal activity within PiCo during swallow and breathing coordination. This can involve recording and analyzing the firing patterns of PiCo neurons in response to different stimuli or conditions. Neurotransmitter Modulation: Investigating the specific neurotransmitter systems involved in PiCo function and their modulation during swallow coordination. This can include pharmacological studies targeting these neurotransmitter systems to understand their role in regulating swallow motor patterns. Functional Imaging: Utilizing functional imaging techniques such as fMRI or optogenetics to visualize and manipulate PiCo activity in real-time during swallow and breathing coordination. This can provide valuable insights into the neural circuits and pathways involved in these processes. Clinical Correlations: Establishing correlations between PiCo activity and dysphagia in clinical populations, including OSA patients and individuals with other respiratory and neurological disorders. This can help validate the findings from preclinical studies and guide potential diagnostic and therapeutic strategies for dysphagia management. By delving deeper into the mechanisms and functions of PiCo in swallow coordination, researchers can uncover novel insights into the neural control of swallowing and breathing, paving the way for advancements in the diagnosis and treatment of dysphagia in various clinical conditions.