Comparison of receptor expression and cholecystokinin signaling between left and right nodose ganglia

The bilateral vagus nerves play a critical role in autonomic control and feeding behavior. The left and right vagi innervate different portions of the gastrointestinal tract with recent reports suggesting functional differences between left and right vagal afferents. Vagal afferents originating in the nodose ganglia (NG) detect mechanical and chemical cues, including gut peptides such as cholecystokinin (CCK), which promotes satiation via the CCK1 receptor (CCK1R). Recent work demonstrates that CCK1R-expressing afferents are more abundant and responsive in right NG, but the cellular mechanisms underlying this asymmetry remain unclear. Most CCK1R-containing vagal afferent neurons co-express the cation channel transient receptor potential vanilloid subtype 1 (TRPV1), which contributes to CCK-induced activation of vagal afferent neurons and may explain differences in signaling between the left and right vagal populations. Moreover, the lateralized expression and function of other receptors important to feeding remains to be investigated. Here, we assessed receptor and ion channel expression in left and right NG using NanoString mRNA profiling and examined functional responses to CCK and TRPV1 agonist capsaicin with fluorescent calcium imaging. We found that the left NG showed greater gene expression for TRP channels, including TRPV1, and contained a greater number of TRPV1+ afferents. Meanwhile, right NG had greater expression of the hormone receptor CCK1R and exhibited enhanced calcium responses to CCK. Together, these results identify key differences in receptor/ion channel expression and function between left and right vagal afferents, advancing our understanding of the cellular mechanisms behind lateralized vagal signaling.<b>NEW & NOTEWORTHY</b> The left and right vagus nerves control feeding but innervate different parts of the gastrointestinal tract, suggesting differences between left and right vagal afferents and their signaling. We assessed gene expression and functional responses from left and right vagus nerves. We found the left vagus had greater expression of TRP channels, whereas the right vagus had more hormone receptors and exhibited enhanced responses to CCK. These differences advance our understanding of lateralized vagal signaling.