Date on Master's Thesis/Doctoral Dissertation

12-2018

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)

Lundy, Robert

Committee Member

Lundy, Robert

Committee Member

Samuelsen, Chad

Committee Member

Guido, William

Committee Member

McCall, Maureen

Committee Member

Petruska, Jeffrey

Author's Keywords

BDNF; TrkB; chorda tympani nerve; geniculate ganglion

Abstract

In the geniculate ganglion, taste neurons likely differentiate into subtypes during development, but very little is known about how these neurons are defined molecularly or how they differentiate. Embryonically, geniculate neuron development is regulated by the growth factor, brain ­derived neurotrophic factor (BDNF). Postnatally, BDNF becomes restricted to subpopulations of taste receptor cells with specific functions, primarily sour responding. I hypothesized that during development, the receptor for BDNF, tropomyosin kinase B receptor (TrkB), also becomes restricted to a neuronal subset. I used transgenic mouse models to label and quantify both geniculate sensory neurons (Phox2b+), and those expressing TrkB (GFP) across developmental age and in conditional TrkB knockouts. I found that TrkB expression and dependence divides oral cavity projecting neurons into three subpopulations: 1) neurons that continue to express TrkB into adulthood and are TrkB-dependent during development (50%), 2) neurons dependent on TrkB during development but that downregulate TrkB expression between E15.5 and E17.5 (41%), and 3) neurons that never express or depend on TrkB (9%). This small population of TrkB independent neurons failed to innervate any of the remaining taste buds, indicating that they may be non-taste somatosensory neurons. It is unclear what the function of TrkB was in the 50% of neurons that continued to express TrkB in adulthood, but it could regulate neuronal function similar to its role in the adult CNS. To answer this question, I examined taste function in both chorda tympani (CT) whole nerve responses and brief-access behavioral tests after blocking TrkB-signaling. TrkB-signaling was blocked using a chemical-genetic approach in which mice with a point mutation in the TrkB (TrkBF616A ) signaling domain cause it to bind the chemical 1-NMPP1, which blocks signaling. Following administration of 1-NMPP1, CT responses were reduced for specific taste stimuli including NH4Cl and sour stimuli (citric acid and HCl). Following conditioned taste aversion learning to 10 mM citric acid, TrkBF616A mice treated with 1-NMPP1 had higher lick rates than vehicle treated mice to low citric acid concentrations, a finding consistent with reduced sensitivity. Functional changes were not due to changes in the morphology of TrkB fibers in the taste buds. I conclude that one adult role of BDNF-TrkB signaling in the taste bud is to directly regulate taste function.

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