Internal senses of the vagus nerve

Abstract

The vagus nerve is an indispensable body-brain connection that controls vital aspects of autonomic physiology like breathing, heart rate, blood pressure, and gut motility, reflexes like coughing and swallowing, and survival behaviors like feeding, drinking, and sickness responses. Classical physiological studies and recent molecular/genetic approaches have revealed a tremendous diversity of vagal sensory neuron types that innervate different internal organs, with many cell types remaining poorly understood. Here, we review the state of knowledge related to vagal sensory neurons that innervate the respiratory, cardiovascular, and digestive systems. We focus on cell types and their response properties, physiological/behavioral roles, engaged neural circuits and, when possible, sensory receptors. We are only beginning to understand the signal transduction mechanisms used by vagal sensory neurons and upstream sentinel cells, and future studies are needed to advance the field of interoception to the level of mechanistic understanding previously achieved for our external senses.

Figure 1.. Anatomy of the sensory vagus nerve.

The cell bodies of vagal sensory neurons reside in left and right ganglia at the base of the neck, with each sensory neuron extruding a single, long, and pseudounipolar axon that targets both the periphery and brain. Collectively, vagal sensory neurons target numerous organs within the body.

Figure 2.. Comparative anatomy of cranial ganglia and branches in mice and human.

Sensory ganglia and branches of cranial nerves IX (glossopharyngeal) and X (vagus) are depicted in relation to nearby anatomical structures. Adult mice display a fused nodose-petrosal-jugular superganglion (left); in some animals, the superior cervical ganglion (here depicted separately) is additionally fused into the superganglion. In humans (right), vagal and petrosal ganglia are distinct anatomical structures. SLN: superior laryngeal nerve. R: rostral. C: caudal. D: dorsal. V: ventral.

Figure 3.. Innervation of the great arteries.

Sensory neurons in the great arteries mediate classical reflexes including the baroreceptor reflex and hypoxic ventilatory response. Vagal afferents reach the aortic arch and subclavian artery via the aortic depressor nerve (ADN), which branches from the superior laryngeal nerve (SLN). Glossopharyngeal afferents reach the carotid body and sinus via the carotid sinus nerve (CSN), which branches from the main glossopharyngeal trunk.

Figure 4.. Examples of sensory terminals involved in interoception.

Vagal and glossopharyngeal sensory neurons include second-order chemosensory neurons that receive inputs from upstream sentinel cells, including glomus cells, taste cells, neuroepithelial bodies, and enteroendocrine cells, as well as mechanosensory neurons that form IGLEs and end-net endings. Various neuron types project to different organs, directly or indirectly detect different stimuli, display different terminal morphologies, and evoke different physiological responses.