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dc.contributor.advisorGinty, David
dc.contributor.authorUmans, Benjamin D.
dc.date.accessioned2019-12-11T10:05:22Z
dash.embargo.terms2021-11-01
dc.date.created2019-11
dc.date.issued2019-09-10
dc.date.submitted2019
dc.identifier.citationUmans, Benjamin D. 2019. Vagal Afferent Pathways of Laryngeal and Gastric Sensation. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:42013123*
dc.description.abstractThe vagus nerve is a key route by which autonomic sensory information is relayed to the brainstem to elicit appropriate physiological and behavioral reflexes. Diverse roles of vagal afferents across physiological systems have been investigated for over a century, but we have only recently begun to understand the cellular variety underlying the transduction and encoding of peripheral cues. A systematic characterization of vagal sensory neurons would enable rational design of genetic tools for dissection of sensory circuits and yield molecular targets for selective manipulation of sensory pathways. We generated a detailed single-cell transcriptional atlas of the vagal sensory ganglion, allowing us to survey both the wide range and regular patterns of gene expression in vagal sensory neurons and to undertake guided investigations linking neurons and the genes they express to physiology. In this dissertation I describe three studies based on this cellular atlas. Sensory innervation of the upper airway is exclusively vagal, and a complete vagal atlas allowed us to systematically characterize the contributions of specific afferent types to airway protection. We linked six neuron types to distinct patterns of laryngeal innervation and identified a single population, a subset of neurons that express P2ry1, as sufficient and necessary for chemically evoked airway protection. P2RY1 neurons innervate specialized laryngeal taste buds, and classical taste signaling via P2x2/3 is required for reflex protection from laryngeal water. These studies clarify the roles of distinct afferent pathways for airway protection and may aid future efforts to therapeutically augment laryngeal protection in vulnerable populations. A cell type-specific approach provided the basis for investigating two genes, Piezo2 and Tmc3, in stomach stretch sensation, which is critical for regulating feeding. We found that Piezo2 expression defines a lineage of neurons that sense gastric distension, but Piezo2 is not required for transduction of stomach stretch. Tmc3 is also not required for stomach stretch sensation or normal feeding behavior. These experiments outline an approach for evaluating candidate mechanosensors and provide important information about these candidates. Taken together, these studies provide a framework for using cell-level expression data to advance our understanding of autonomic physiology.
dc.description.sponsorshipMedical Sciences
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectvagal
dc.subjectvagus
dc.subjectcough
dc.subjectswallowing
dc.subjectnodose
dc.subjectjugular
dc.subjectairway protection
dc.subjectlarynx
dc.subjectP2ry1
dc.subjectTmc3
dc.subjectPiezo2
dc.subjectinteroception
dc.subjectsensory neuroscience
dc.subjectcell type
dc.subjectsingle-cell
dc.subjectoptogenetics
dc.subjectstomach stretch
dc.subjectsatiety
dc.subject
dc.titleVagal Afferent Pathways of Laryngeal and Gastric Sensation
dc.typeThesis or Dissertation
dash.depositing.authorUmans, Benjamin D.
dash.embargo.until2021-11-01
dc.date.available2019-12-11T10:05:22Z
thesis.degree.date2019
thesis.degree.grantorGraduate School of Arts & Sciences
thesis.degree.grantorGraduate School of Arts & Sciences
thesis.degree.levelDoctoral
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
thesis.degree.nameDoctor of Philosophy
dc.contributor.committeeMemberCorey, David
dc.contributor.committeeMemberDatta, Sandeep
dc.contributor.committeeMemberCanning, Brendan
dc.type.materialtext
thesis.degree.departmentMedical Sciences
thesis.degree.departmentMedical Sciences
dash.identifier.vireo
dc.identifier.orcid0000-0002-8209-9731
dash.author.emailben.umans@gmail.com


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