Table 1.
Genetically-identified Vagal Sensory Neuron Populations and their Target Regions in the Gut.
| Primary Marker | Subpopulation Markers | Innervation Terminals | Site of Innervation | Response to Stimuli | Function | References |
|---|---|---|---|---|---|---|
| Calca+ (CGRP, Feeding-Modulating Neurons) | General Calca+ | Mucosal endings, IGLEs | Stomach, small intestine | Responds to nutrient detection and stretch | Modulates feeding behavior, reduces food intake upon activation | (Bai et al. 2019; W. S. Kim et al. 2021) |
| Calca+, Gfra1+ | IMAs | Stomach | Transient response to stretch | Mechanosensation, detecting muscle tension | (Zhao et al. 2022) | |
| Calca+, Gfra1+, P2ry1+ | IMAs | Stomach | Transient response to stretch | Gut-brain feedback | (Zhao et al. 2022) | |
| Calca+, Gfra1+, Drd2+ | IMAs | Stomach | Transient response to stretch | Dopamine-mediated gut-brain signaling | (Zhao et al. 2022) | |
| Trpa1+ (Nociceptive, Fat-Sensing, and Inflammatory Neurons) | General Trpa1+ | Mucosal endings, submucosal & myenteric plexus | Stomach, colon | Responds to irritants, inflammatory pain | Nociception, gut-brain protective reflexes | (Bai et al. 2019; Patil et al. 2023) |
| Trpa1+, Npas1+ | IMAs | Stomach | Transient response to stretch | Mechanosensation, detecting muscle tension | (Zhao et al. 2022) | |
| Trpa1+, Drd2+, Car8+ | IMAs | Stomach | Transient response to stretch | Dopamine-related gut-brain interactions | (Zhao et al. 2022) | |
| Trpa1+ (Fat-Sensing) | Mucosal endings | Small intestine | Responds to fat infusion | Drives fat preference behavior | (M. Li et al. 2022a) | |
| Trpa1+ (Inflammation-Responsive) | Mucosal endings, nodose ganglion | Gut | Responds to inflammatory signals | Modulates immune responses | (Ichiki et al. 2022) | |
| Piezo2+ (Mechanosensory, Gastric Stretch Neurons) | General Piezo2+ | IGLEs | Stomach, intestine | Sustained response to stretch | Detects gastric distension, regulates satiety | (Bai et al. 2019; Zhao et al. 2022) |
| Piezo2+, Glp1r+, Rbp4+ | IGLEs | Stomach, duodenum | Sustained response to stretch | Mechanosensation, satiety regulation | (Zhao et al. 2022) | |
| Piezo2+, Lamp5+, Slit2+ | IGLEs | Stomach | Sustained response to stretch | Gastric accommodation, stomach filling regulation | (Zhao et al. 2022) | |
| Htr3a+ (Serotonin-Sensitive, Nausea-Modulating Neurons) | General Htr3a+ | Mucosal endings | Stomach, intestine | Responds to serotonin release from enterochromaffin cells | Controls nausea, emesis, and gut motility | (Bai et al. 2019; S.-H. Kim et al. 2020) |
| Htr3a+, Cckar+, Vip+, Glp1r+ or Uts2b+ | Mucosal terminals | Duodenum | Responds to luminal contents | Chemosensation, nutrient detection | (Zhao et al. 2022) | |
| Htr3a+, Cckar+, Ctxn2+, Oxtr+ | IGLEs | Duodenum | Responds to stretch, possibly polymodal | Mechanosensation and chemosensation | (Zhao et al. 2022) | |
| Tac1+ (Substance P, Osmolality-Sensitive Neurons) | General Tac1+ | Mucosal endings | Primarily jugular ganglion, few in nodose | Nociceptive | Pain-related signaling, gut-brain protective reflexes | (D. Kim et al. 2020) |
| Tac1+ (Osmolality-Sensitive) | Mucosal endings, hepatic portal area | Gut | Responds to hypotonic stimuli | Detection of gut osmolality changes, regulates thirst | (Ichiki et al. 2022) | |
| Gpr65+ (Acid-Sensing, Distension-Sensitive Neurons) | General Gpr65+ | IGLEs | Stomach, intestine | Detects gastric distension | Mechanosensation, satiety regulation | (Bai et al. 2019) |
| Gpr65+, Tmem233+, P2ry1+ | Mucosal endings | Stomach | Responds to chemical stimuli | Chemosensation, detecting luminal contents | (Zhao et al. 2022) | |
| Glp1r+ (Metabolic and Satiety-Regulating Neurons) | General Glp1r+ | IGLEs | Stomach, intestine | Detects gastric stretch, metabolic signals | Mechanosensation, feeding behavior | (Bai et al. 2019; Brierley et al. 2021; E. K. K. Williams et al. 2016; J.-P. Krieger et al. 2016) |
| Glp1r+, Piezo2+, Rbp4+ | IGLEs | Stomach, Duodenum | Sustained response to stretch | Mechanosensation, satiety regulation | (Zhao et al. 2022) | |
| Glp1+, Vip+, Ust2b+ | Mucosal endings | Intestine | Responds to chemical stimuli | Chemosensation, detecting luminal contents | (J. P. Krieger 2020) | |
| Oxtr+ (Mechanosensory, Socially Modulating Neurons) | General Oxtr+ | IGLEs | Stomach, intestine | Responds to stretch & metabolic cues | Mechanosensation, modulates feeding & social behaviors | (Bai et al. 2019; Scott et al. 2025) |
| Oxtr+, Cckar+, Htr3a+ | IGLEs | Duodenum | Responds to stretch | Mechanosensation and chemosensation | (Zhao et al. 2022) | |
| Sst+ (Digestive Regulatory Neurons) | General Sst+ | Mucosal endings | Small intestine | Responds to nutrient content | Chemosensation, digestion regulation | (Bai et al. 2019) |
| Vip+ (Nutrient-Sensing, Gut-Brain Signaling Neurons) | General Vip+ | Mucosal endings | Small intestine | Responds to nutrient detection | Modulates gut-brain metabolic responses | (Bai et al. 2019) |
| Vip+, Cckar+, Glp1r+, Htr3a+ | Mucosal terminals | Duodenum | Responds to luminal contents | Chemosensation, nutrient detection | (Zhao et al. 2022) | |
| Npy2r+ (Energy Balance-Regulating Neurons) | General Npy2r+ | IGLEs & mucosal endings | Stomach, intestine | Inhibits vagal activity during fasting | Energy balance regulation, satiety | (Bai et al. 2019) |
| Cart+ (Gut-Brain Signaling Neurons) | Cart+, Oxtr+, Ctxn2+ | IGLEs | Stomach and intestine | Responds to intestinal stretch | Inhibit food intake, slow gastric emptying, increase BAT thermogenesis | (Singh et al. 2021; de Araujo et al 2023) |
| Cart+, Sst+ | Mucosal endings | Stomach | Presumably response to stroking | TBD | (Singh et al. 2021) | |
| Cart+, Vip+, utsb2+ | Mucosal endings | Intestine | Respond to luminal nutrients | Increase preference via memory, motivation and reinforcement learning | (Singh et al. 2021; de Araujo et al 2023) | |
| Cart+, Calca+ | Mucosal endings | Stomach | Presumably transient response to stretch | TBD | (Singh et al. 2021) |