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Genetic tracing of Nav1.8-expressing vagal afferents in the mouse.

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.

Pubmed ID: 21618224

Authors

  • Gautron L
  • Sakata I
  • Udit S
  • Zigman JM
  • Wood JN
  • Elmquist JK

Journal

The Journal of comparative neurology

Publication Data

October 15, 2011

Associated Grants

  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB/F000227/1
  • Agency: NIDDK NIH HHS, Id: DK088761-01
  • Agency: Medical Research Council, Id: G0901905
  • Agency: NIDDK NIH HHS, Id: P01 DK088761
  • Agency: NIDDK NIH HHS, Id: PL1 DK081182
  • Agency: NIDDK NIH HHS, Id: PL1 DK081182
  • Agency: NIDDK NIH HHS, Id: PL1 DK081182-01
  • Agency: NIDA NIH HHS, Id: R01 DA024680
  • Agency: NIDA NIH HHS, Id: R01 DA024680
  • Agency: NIDA NIH HHS, Id: R01 DA024680-05
  • Agency: NIDDK NIH HHS, Id: R01 DK53301
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185-05
  • Agency: NCRR NIH HHS, Id: UL1 RR024923
  • Agency: NCRR NIH HHS, Id: UL1 RR024923
  • Agency: NCRR NIH HHS, Id: UL1 RR024923-01

Mesh Terms

  • Afferent Pathways
  • Animals
  • Fluorescent Dyes
  • Ghrelin
  • Glucagon
  • Glucagon-Like Peptide 1
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myenteric Plexus
  • NAV1.8 Voltage-Gated Sodium Channel
  • Neurons, Afferent
  • Sodium Channels
  • Vagus Nerve