The rostral brainstem's pivotal role in swallow‐breathing coordination

Abstract

Respiration and swallowing are motor behaviours that require the interaction of two brainstem central pattern generators (r‐CPG, sw‐CPG). Previously we studies the interaction of swallowing and breathing in the in situ perfused brainstem preparation that identified a pivotal role of the pontine Kolliker‐Fuse nuclei for the mediation of protective glottal closure. We recently developed a computational model to further aid and test network connectivity and neural interaction between sw‐ and r‐CPGs. The model is based on a stepwise integration of synaptic connectivity between central sensory relay, sw‐ and r‐CPG neuron populations. The model is validated by experimental data obtained in situ. In the model and experimental data, stimulation of the superior laryngeal nerve (SLN, 10s) reliably triggers sequential swallowing with concomitant swallowing‐related glottal closure and suppression of inspiratory activity. Short SLN stimulation (100ms) evokes single swallows and respiratory phase resetting in the model and in situ yielding comparable phase response curves. Consistent with experiments, numerical circuit‐busting simulations show that deletion of ponto‐medullary synaptic interactions triggers apneusis and eliminates swallowing‐related glottal closure during sequential swallowing. Additionally, systematic variations of the synaptic strengths of distinct network connections predict vulnerable network connections that can mediate clinically relevant breathing‐swallowing disorders observed in the elderly and patients with neurodegenerative disease. Thus, the present model provides novel insights that can guide future experiments and the development of efficient treatments for prevalent breathing‐swallowing disorders.