Date on Master's Thesis/Doctoral Dissertation

5-2023

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Krimm, Robin

Committee Co-Chair (if applicable)

McGee, Aaron

Committee Member

McGee, Aaron

Committee Member

Samuelsen, Chad

Committee Member

Borghuis, Bart

Committee Member

Stirling, David

Author's Keywords

neuroplasticity; taste bud; peripheral neuron

Abstract

The continual replacement of taste cells creates interesting questions regarding how the innervating neurons are impacted during this process. Here we ask how innervation within taste buds is affected when taste cell entry is inhibited and reestablished. Inhibition of sonic hedgehog signaling (Shh) is thought to inhibit taste cell turnover. Consistently, fewer new cells were added to individual taste buds after treatment with a Shh-inhibitor compared to vehicle treatment, and taste bud volume decreased after 16 days of treatment. We next examined how taste nerve fiber extension into the gustatory epithelium is affected by preventing taste cell turnover. Ten days of Shh inhibitor caused a loss of innervation in the epithelium of fungiform papillae. Seven days of recovery does not restore fibers within the epithelium, suggesting that recovery of normal branch morphology requires more than 7 days of cell turnover. These results provide evidence for the hypothesis that normal branch morphology within the taste bud is supported by taste cell turnover and provide a pharmacologic manipulation for controlling taste cell entry into taste buds. The perception of taste relies on new taste bud cells integrating with existing neural circuitry, yet how these new cells connect with a taste ganglion neuron is unknown. Do taste ganglion neurons remodel to accommodate taste bud cell renewal? If so, how much of the taste axon structure is fixed and how much remodels? Here we measured the motility and branching of individual taste arbors (the portion of the axon innervating taste buds) over time with two-photon in vivo microscopy. Terminal branches of taste arbors continuously and rapidly remodel within the taste bud. This remodeling is faster than predicted by taste bud cell renewal, with terminal branches added and lost concurrently. Surprisingly, ablating new taste cells with chemotherapeutic agents revealed that remodeling of the terminal branches of taste arbors does not rely of the renewal of taste bud cells. Although the arbor structure remodeling was fast and intrinsically controlled, no new arbors were added, and few were lost over 100 days. Taste ganglion neurons maintain a stable number of nerve arbors that are each capable of high-speed remodeling. Arbor structural plasticity would permit arbors to locate new taste bud cells, while stability of arbor number could support constancy in the degree of connectivity and function for each neuron over time.

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