The vagal sensory pathway plays a critical role in conveying internal bodily states to the brain. Vagal sensory neurons reside in nodose ganglia, and their axons bifurcate into two branches. The peripheral branch travels through the vagus nerve, which is the longest cranial nerve and meanders throughout the abdomen and thorax, to detect signals from the gut, liver, pancreas, lung, and heart. The central branch, on the other hand, projects to the brain and relays visceral signals to the nucleus of the solitary tract (NTS) [1], [2]. This body-vagal-brain connection is essential for physiological functions such as digestion, metabolism, the immune system, respiration, and the cardiovascular system.

Vagal sensory neurons detect diverse internal signals. Anatomically, they project to a variety of visceral organs and form specialized terminals within different tissue layers, such as the intramuscular arrays (IMAs) within the muscle layer of the gut wall, the intraganglionic laminar endings (IGLEs) within the myenteric plexus, and the mucosal endings within the intestinal villi [1], [3], [4], [5]. Some of them also interact with specialized sentinel cells, such as the laryngeal taste cells, the neuroepithelial bodies (NEBs) of the lung, and the enteroendocrine cells (EECs) of the intestine [6]. Importantly, these terminal structures enable vagal sensory neurons to detect diverse physiological signals, varying from mechanical stimuli such as stroking of the gut lumen and distension of the gut wall, to different chemicals such as nutrients, osmolytes, hormones, and bacterial products[1], [3], [4], [7], [8]. Vagal afferents transmit these signals to the central nervous system with a broad range of conduction velocities and innervate different target regions within the NTS of the brainstem [1], [2].

The heterogeneity of vagal sensory neurons has hindered our understanding of vagal regulatory mechanisms. Early descriptive classifications were unable to relate the anatomical structures of vagal neurons to their response properties and physiological functions. Furthermore, traditional vagotomy approaches [3], [9] or bulk stimulation [3], [10] do not target or distinguish individual sensory subtypes carrying specific information. Recently, several independent studies have characterized the molecular identities of vagal sensory neurons, enabling genetic access to investigate the function of different vagal subtypes [3], [11], [12], [13], [14], [15], [16]. In this review, we discuss the recent molecular genetic approaches used to characterize vagal sensory subtypes and review how different methods facilitate our understanding of the vagal sensory pathway in gut-brain communication.