Molecular profiling of murine sensory neurons in the nodose and dorsal root ganglia labeled from the peritoneal cavity

Abstract

Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. To elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488-conjugated cholera toxin B allowed enrichment for neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser-capture microdissection. Gene expression profiles of these afferent neurons, obtained by microarray hybridization, were analyzed using multivariate spectral map analysis, significance analysis of microarrays (SAM) algorithm, and fold-difference filtering. A total of 1,996 genes were differentially expressed in DRG vs. NG, including 41 G protein-coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia, demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, we provide a detailed catalog of all adrenergic and cholinergic, GABA, glutamate, serotonin, and dopamine receptors; voltage-gated potassium, sodium, and calcium channels; and transient receptor potential cation channels present in afferents projecting to the peritoneal cavity. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacological agents modulating visceral sensation.

Neural and behavioral responses to low-grade inflammation

“…This is similar to our previous report that indicated localized inflammation induces location-specific response only in the PVN, not in the NTS and VLM [31]. Although vagal afferents are critical for transmitting sensory signals from the peritoneal cavity, recent studies showed that spinal afferents from the peritoneal cavity can also be activated by sensory inputs [32]. It is possible the direct spinohyothalamic pathway [33] can mediate CNS signaling by low-grade inflammation.…”

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

“…Nodose sensory neurons express many thermosensitive TRPs (thermoTRPs), including TRPV1, TRPM8, and TRPA1 (Zhang et al, 2004;Bielefeldt et al, 2006;Ni et al, 2006;Peeters et al, 2006). Using calcium fluorimetry, Zhang et al (2004) reported cold-evoked responses in a small fraction of mice nodose neurons but the possible underlying mechanisms was not addressed (Zhang et al, 2004).…”

Molecular development of the extrinsic sensory innervation of the gastrointestinal tract

“…The neurons of the nodose ganglia are derived from the placodal ectoderm while DRG neurons differentiate from cells that migrated from the thoracic level of the neural crest (Le Douarin and Kalcheim, 1999). Molecular profiling studies have shown that many genes, including G protein-coupled receptors and ion channels, are differentially expressed in adult mouse nodose ganglia and thoracic DRG (Peeters et al, 2006). Axons from both the nodose ganglia and the DRG grow into the gut during development to find their correct targets in the bowel wall, but given the described similarities and differences between the two types of ganglia, it is reasonable to expect that there will be similarities and differences in terms of the molecules and mechanisms by which each is guided.…”

“…For example, both vagal and spinal afferents have endings in the myenteric plexus (Peeters et al, 2006). How the connections between the extrinsic and intrinsic nervous systems form, and how the development of each affects the other, is unknown.…”