Coding of Internal Senses: Vagal Gut-to-Brain Circuits
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CitationWilliams, Erika Kristen. 2016. Coding of Internal Senses: Vagal Gut-to-Brain Circuits. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractOur ability to detect features of environments in and around us is fundamental. Organisms have developed highly specialized systems to allow for transduction of a broad variety of stimuli to convey sensory information to the nervous system. In addition to traditionally appreciated external sensory systems, such as sight, smell, taste and touch, organisms also posses internal sensory systems to detect changes in physiological state. One key body-to-brain connection is via cranial nerve X, the vagus nerve. The vagus nerve innervates most major organ systems, transmits information from peripheral organs to the brainstem, and plays a critical role in the regulation of diverse physiological processes. However, the organization of this sensory system, and direct links between response properties, terminal morphology, and signaling mechanisms is not currently available for many vagal neuron types.
To study the peripheral representation of autonomic inputs, we developed a vagal ganglion imaging preparation for large-scale parallel analysis of single neuron responses in vivo. Using this preparation, we can record responses evoked by a broad array of peripherally applied stimuli, including stretch in the lung, stomach, and intestine, responses to inhaled carbon dioxide, and to chemical cues perfused through the intestinal lumen. This work allows for a careful description of response properties of vagal sensory neurons, and their organization within the ganglion.
Furthermore, to link response properties of vagal sensory neuron subsets to specific anatomical phenotypes and physiological roles, we developed a genetic strategy to molecularly define neuron subsets in the context of in vivo imaging. We identified one neuron subset marked by the gut hormone receptor Glp1r that responds to mechanical distension in the gastrointestinal tract, forms stereotyped mechano-sensitive terminals, and whose activation increases gastric pressure. A second neuron subset, marked by Gpr65, detects chemical cues in the intestine, projects into intestinal villi, and causes cessations of gastric contractions. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33493310
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