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

Laurent Gautron, Ichiro Sakata, Swalpa Udit, Jeffrey M. Zigman, John N. Wood, Joel K. Elmquist

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3085-3101
Number of pages17
JournalJournal of Comparative Neurology
Volume519
Issue number15
DOIs
StatePublished - Oct 15 2011

Fingerprint

Enteroendocrine Cells
Sensory Receptor Cells
Visceral Afferents
Neurons
Afferent Neurons
Myenteric Plexus
Mechanoreceptors
Ghrelin
Glucagon-Like Peptide 1
Viscera
Sodium Channels
Tetrodotoxin
Glucagon
Pancreas
Mucous Membrane
Thorax
Fluorescence
Technology
Pain
Muscles

Keywords

  • Autonomic nervous system
  • Connections
  • Obesity
  • Transgenic
  • Vagotomy
  • Visceral pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Genetic tracing of Nav1.8-expressing vagal afferents in the mouse. / Gautron, Laurent; Sakata, Ichiro; Udit, Swalpa; Zigman, Jeffrey M.; Wood, John N.; Elmquist, Joel K.

In: Journal of Comparative Neurology, Vol. 519, No. 15, 15.10.2011, p. 3085-3101.

Research output: Contribution to journalArticle

@article{2c31fa7dbfe9422d858e7d58f8e5e894,
title = "Genetic tracing of Nav1.8-expressing vagal afferents in the mouse",
abstract = "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.",
keywords = "Autonomic nervous system, Connections, Obesity, Transgenic, Vagotomy, Visceral pain",
author = "Laurent Gautron and Ichiro Sakata and Swalpa Udit and Zigman, {Jeffrey M.} and Wood, {John N.} and Elmquist, {Joel K.}",
year = "2011",
month = "10",
day = "15",
doi = "10.1002/cne.22667",
language = "English (US)",
volume = "519",
pages = "3085--3101",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "15",

}

TY - JOUR

T1 - Genetic tracing of Nav1.8-expressing vagal afferents in the mouse

AU - Gautron, Laurent

AU - Sakata, Ichiro

AU - Udit, Swalpa

AU - Zigman, Jeffrey M.

AU - Wood, John N.

AU - Elmquist, Joel K.

PY - 2011/10/15

Y1 - 2011/10/15

N2 - 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.

AB - 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.

KW - Autonomic nervous system

KW - Connections

KW - Obesity

KW - Transgenic

KW - Vagotomy

KW - Visceral pain

UR - http://www.scopus.com/inward/record.url?scp=79960737256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960737256&partnerID=8YFLogxK

U2 - 10.1002/cne.22667

DO - 10.1002/cne.22667

M3 - Article

VL - 519

SP - 3085

EP - 3101

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 15

ER -