Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood.

Many basic characteristics of gustatory neurons remain unknown, partly due to the absence of specific markers. Some neurons in the geniculate ganglion project to taste regions in the oral cavity, whereas others innervate the outer ear. We hypothesized that the transcription factor Phox2b would identify oral cavity-projecting neurons in the geniculate ganglion. To test this possibility, we characterized mice in which Phox2b-Cre mediated gene recombination labeled neurons with tdTomato. Nerve labeling revealed that all taste neurons projecting through the chorda tympani (27%) and greater superficial petrosal nerves (15%) expressed Phox2b during development, whereas non-oral somatosensory neurons (58%) in the geniculate ganglion did not. We found tdTomato-positive innervation within all taste buds. Most (57%) of the fungiform papillae had labeled innervation only in taste buds, whereas 43% of the fungiform papillae also had additional labeled innervation to the papilla epithelium. Chorda tympani nerve transection eliminated all labeled innervation to taste buds, but most of the additional innervation in the fungiform papillae remained. Some of these additional fibers also expressed tyrosine hydroxylase, suggesting a sympathetic origin. Consistent with this, both sympathetic and parasympathetic fibers innervating blood vessels and salivary glands contained tdTomato labeling. Phox2b-tdTomato labels nerve fascicles in the tongue of the developing embryo and demonstrates a similar stereotyped branching pattern DiI-labeling.