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Genetic tracing of Nav1.8‐expressing vagal afferents in the mouse
Author(s) -
Gautron Laurent,
Sakata Ichiro,
Udit Swalpa,
Zigman Jeffrey M.,
Wood John N.,
Elmquist Joel K.
Publication year - 2011
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22667
Subject(s) - biology , enteroendocrine cell , nodose ganglion , vagus nerve , neuroscience , anterograde tracing , sensory system , retrograde tracing , myenteric plexus , anatomy , receptor , free nerve ending , endocrinology , endocrine system , central nervous system , immunohistochemistry , stimulation , biochemistry , hormone , immunology
Nav1.8 is a tetrodotoxin‐resistant sodium channel present in large subsets of peripheral sensory neurons, including both spinal and vagal afferents. In spinal afferents, Nav1.8 plays a key role in signaling different types of pain. Little is known, however, about the exact identity and role of Nav1.8‐expressing vagal neurons. Here we generated mice with restricted expression of tdTomato fluorescent protein in all Nav1.8‐expressing afferent neurons. As a result, intense fluorescence was visible in the cell bodies, central relays, and sensory endings of these neurons, revealing the full extent of their innervation sites in thoracic and abdominal viscera. For instance, vagal and spinal Nav1.8‐expressing endings were seen clearly within the gastrointestinal mucosa and myenteric plexus, respectively. In the gastrointestinal muscle wall, labeled endings included a small subset of vagal tension receptors but not any stretch receptors. We also examined the detailed innervation of key metabolic tissues such as liver and pancreas and evaluated the anatomical relationship of Nav1.8‐expressing vagal afferents with select enteroendocrine cells (i.e., ghrelin, glucagon, GLP‐1). Specifically, our data revealed the presence of Nav1.8‐expressing vagal afferents in several metabolic tissues and varying degrees of proximity between Nav1.8‐expressing mucosal afferents and enteroendocrine cells, including apparent neuroendocrine apposition. In summary, this study demonstrates the power and versatility of the Cre‐LoxP technology to trace identified visceral afferents, and our data suggest a previously unrecognized role for Nav1.8‐expressing vagal neurons in gastrointestinal functions. J. Comp. Neurol. 519:3085–3101, 2011. © 2011 Wiley‐Liss, Inc.