Untangling axons: distinguishing the geniculate ganglion and trigeminal ganglion contributions to mechanosensory innervation of the tongue

Abstract

Oral mechanosensation underlies feeding, speech, and grooming, yet our understanding of the neurons and their terminals in the oral cavity remains limited. The trigeminal ganglion (TG) and geniculate ganglion (GG) provide mechanosensory innervation to the tongue, but their individual contributions anatomically and functionally are unknown. We employed intersectional genetics to distinguish RET-expressing TG and GG neurons, combined with immunolabeling and selective nerve transections to map innervation patterns in fungiform, filiform, and circumvallate papillae of the tongue. Contrary to dogma, both GG and TG fibers innervate filiform papillae, extragemmal fungiform regions, and taste buds. Reporter mice were generated to observe cells expressing RET ligands that would be innervated by these neurons, allowing identification of possible end-organ structures. Nerve transection experiments revealed that extragemmal GFRα1⁺ fibers derive mostly from TG, whereas intragemmal GFRα3⁺ fibers originate from GG. FM1-43 labeling, which detects the activated mechanosensory receptor PIEZO2 in nerve terminals, showed that tactile stimuli and consumption of foods with varying textures selectively activate GFRα1+ and, to a lesser extent, GFRα3+ fibers in distinct regions of papillae. These findings redefine oral mechanosensory wiring, highlighting complex ganglion-specific patterns and RET ligand-receptor pairing shaping texture perception. Significance statement Oral mechanosensation underlies our perception of food texture during feeding, and is critical for mastication and speech. The trigeminal ganglion (TG) and geniculate ganglion (GG) provide mechanosensory innervation to the tongue, but their individual anatomic contributions are unknown. Using molecular-genetic techniques, we unraveled the innervation of the surface papillae of the tongue by GG and TG. FM1-43 labeling, which detects the activated mechanosensory PIEZO2 receptor in nerve terminals, revealed that consumption of foods with varying textures selectively activates axon terminals in distinct regions of papillae. These findings redefine the wiring of oral mechanosensory neurons, highlighting complex ganglion-specific patterns that shape texture perception.