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      Rapid activation of esophageal mechanoreceptors alters the pharyngeal phase of swallow: Evidence for inspiratory activity during swallow

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          Abstract

          Swallow is a complex behavior that consists of three coordinated phases: oral, pharyngeal, and esophageal. Esophageal distension (EDist) has been shown to elicit pharyngeal swallow, but the physiologic characteristics of EDist-induced pharyngeal swallow have not been specifically described. We examined the effect of rapid EDist on oropharyngeal swallow, with and without an oral water stimulus, in spontaneously breathing, sodium pentobarbital anesthetized cats ( n = 5). Electromyograms (EMGs) of activity of 8 muscles were used to evaluate swallow: mylohyoid (MyHy), geniohyoid (GeHy), thyrohyoid (ThHy), thyropharyngeus (ThPh), thyroarytenoid (ThAr), cricopharyngeus (upper esophageal sphincter: UES), parasternal (PS), and costal diaphragm (Dia). Swallow was defined as quiescence of the UES with overlapping upper airway activity, and it was analyzed across three stimulus conditions: 1) oropharyngeal water infusion only, 2) rapid esophageal distension (EDist) only, and 3) combined stimuli. Results show a significant effect of stimulus condition on swallow EMG amplitude of the mylohyoid, geniohyoid, thyroarytenoid, diaphragm, and UES muscles. Collectively, we found that, compared to rapid cervical esophageal distension alone, the stimulus condition of rapid distension combined with water infusion is correlated with increased laryngeal adductor and diaphragm swallow-related EMG activity (schluckatmung), and post-swallow UES recruitment. We hypothesize that these effects of upper esophageal distension activate the brainstem swallow network, and function to protect the airway through initiation and/or modulation of a pharyngeal swallow response.

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          Most cited references91

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          Relation between size of neurons and their susceptibility to discharge.

          E HENNEMAN (1957)
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            Brain stem control of swallowing: neuronal network and cellular mechanisms.

            A Jean (2001)
            Swallowing movements are produced by a central pattern generator located in the medulla oblongata. It has been established on the basis of microelectrode recordings that the swallowing network includes two main groups of neurons. One group is located within the dorsal medulla and contains the generator neurons involved in triggering, shaping, and timing the sequential or rhythmic swallowing pattern. Interestingly, these generator neurons are situated within a primary sensory relay, that is, the nucleus tractus solitarii. The second group is located in the ventrolateral medulla and contains switching neurons, which distribute the swallowing drive to the various pools of motoneurons involved in swallowing. This review focuses on the brain stem mechanisms underlying the generation of sequential and rhythmic swallowing movements. It analyzes the neuronal circuitry, the cellular properties of neurons, and the neurotransmitters possibly involved, as well as the peripheral and central inputs which shape the output of the network appropriately so that the swallowing movements correspond to the bolus to be swallowed. The mechanisms possibly involved in pattern generation and the possible flexibility of the swallowing central pattern generator are discussed.
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              Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts.

              The aim of this study was to map the viscerotopic representation of the upper alimentary tract in the sensory ganglia of the IXth and Xth cranial nerves and in the subnuclei of the solitary and spinal trigeminal tracts. Therefore, in 172 rats 0.5-65 microliters of horseradish peroxidase (HRP), wheat germ agglutinin-HRP, or cholera toxin-HRP were injected into the trunks and major branches of the IXth and Xth cranial nerves as well as into the musculature and mucosa of different levels of the upper alimentary and respiratory tracts. The results demonstrate that the sensory ganglia of the IXth and Xth nerves form a fused ganglionic mass with continuous bridges of cells connecting the proximal and distal portions of the ganglionic complex. Ganglionic perikarya were labeled in crude, overlapping topographical patterns after injections of tracers into nerves and different parts of the upper alimentary tract. After injections into the soft palate, pharynx, esophagus, and stomach, anterograde labeling was differentially distributed in distinct subnuclei in the nucleus of the tractus solitarius (NTS). Palatal and pharyngeal injections resulted primarily in labeling of the interstitial and intermediate subnuclei of the NTS and in the paratrigeminal islands (PTI) and spinal trigeminal complex. Esophageal and stomach wall injections resulted in labeling primarily of the subnucleus centralis and subnucleus gelatinosus, respectively. The distribution of upper alimentary tract vagal-glossopharyngeal afferents in the medulla oblongata has two primary groups of components, i.e., a viscerotopic distribution in the NTS involved in ingestive and respiratory reflexes and a distribution coextensive with fluoride-resistant acid-phosphatase-positive regions of the PTI and spinal trigeminal nucleus presumably involved in visceral reflexes mediated by nociceptive or chemosensitive C fibers.

                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 April 2021
                2021
                : 16
                : 4
                : e0248994
                Affiliations
                [1 ] Department of Neurological Surgery and Kentucky Spinal Cord Injury Research Center, College of Medicine, University of Louisville, Louisville, Kentucky, United States of America
                [2 ] Department of Physiology, University of Louisville, Louisville, Kentucky, United States of America
                [3 ] School of Medicine, University of Louisville, Louisville, Kentucky, United States of America
                [4 ] Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America
                National Yang-Ming University, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors share first authorship on this work.

                Author information
                https://orcid.org/0000-0003-4422-3356
                https://orcid.org/0000-0002-9004-3893
                Article
                PONE-D-20-40995
                10.1371/journal.pone.0248994
                8018667
                33798212
                9aaaf5a6-b189-4d2d-a9e9-d8f5b8307fde
                © 2021 Frazure et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 December 2020
                : 9 March 2021
                Page count
                Figures: 2, Tables: 2, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: HL111215
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NS110169
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100005191, Craig H. Neilsen Foundation;
                Award ID: CNF546714
                Award Recipient :
                Funded by: The Kentucky Spinal Cord and Head Injury Research Trust
                Award Recipient :
                Funded by: The University of Louisville Summer Research Scholar Program
                Award Recipient :
                Funded by: The Commonwealth of Kentucky Challenge for Excellence
                Award Recipient :
                Funded by: The Giles F. Filley Family
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: T32 HL105355
                Award Recipient :
                Funded by: The American Physiological Society and the Giles F. Filley Family
                Award Recipient :
                This study was funded by the National Institutes of Health to TP (HL111215 and NS110169) and AB (T32 HL105355), the Kentucky Spinal Cord and Head Injury Research Trust to TP, the University of Louisville Summer Research Scholar Program to TP, The Commonwealth of Kentucky Challenge for Excellence to TP, and the Craig F. Neilsen Foundation to TP (CNF546714), The American Physiological Society to TP, and the Giles F. Filley Family to TP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Ingestion
                Swallowing
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Esophagus
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Esophagus
                Biology and Life Sciences
                Anatomy
                Neck
                Throat
                Larynx
                Medicine and Health Sciences
                Anatomy
                Neck
                Throat
                Larynx
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Electrophysiological Techniques
                Muscle Electrophysiology
                Electromyography
                Biology and Life Sciences
                Anatomy
                Respiratory System
                Thoracic Diaphragm
                Medicine and Health Sciences
                Anatomy
                Respiratory System
                Thoracic Diaphragm
                Biology and Life Sciences
                Neuroscience
                Reflexes
                Biology and Life Sciences
                Physiology
                Muscle Physiology
                Muscle Contraction
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Psychology
                Perception
                Sensory Perception
                Sensory Receptors
                Biology and Life Sciences
                Psychology
                Cognitive Psychology
                Perception
                Sensory Perception
                Sensory Receptors
                Social Sciences
                Psychology
                Cognitive Psychology
                Perception
                Sensory Perception
                Sensory Receptors
                Biology and Life Sciences
                Neuroscience
                Sensory Perception
                Sensory Receptors
                Biology and Life Sciences
                Cell Biology
                Signal Transduction
                Sensory Receptors
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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