Publication Date

2018-11-27

Availability

Embargoed

Embargo Period

2020-11-26

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Neuroscience (Medicine)

Date of Defense

2018-08-24

First Committee Member

Nirupa Chaudhari

Second Committee Member

H. Peter Larsson

Third Committee Member

Alejandro Caicedo

Fourth Committee Member

Timothy Gilbertson

Fifth Committee Member

Vittorio Porciatti

Abstract

Taste cells detect five different gustatory modalities: sweet, sour, bitter, umami, and salty. The mechanisms, cells and transductional events that underlie sweet, sour, bitter and umami taste are well characterized. However, salt taste is poorly understood. The ability to detect NaCl is partially, but not fully, blocked by the diuretic amiloride. In both taste buds and in kidneys, a primary target of amiloride is the epithelial sodium channel (ENaC). As such, the field has interpreted amiloride sensitive salt taste to rely on Na+ influx through ENaCs while another unknown receptor detects amiloride-insensitive salt taste. The cell type(s), mechanisms and cell-signaling events in taste bud cells that detect and process salty stimuli in either amiloride-sensitive or insensitive pathways remain unclear. The present work characterizes NaCl taste responses in semi-intact taste buds to define cells critical for salt detection and components of NaCl taste signaling pathways. In the second half of my dissertation, I examine two drugs of abuse that alter food intake behavior and lead to pronounced weight loss. I look at the drug cocaine, which is associated with a decreased consumption of sweet and carbohydrate-rich foods, and nicotine, which shows evidence of increased salt consumption. For both of these drugs, chronic use is associated with a change in dietary preference, but it is unknown whether these drugs directly affect the taste system. To test whether chronic exposure to either cocaine or nicotine impacts taste, I test lick responses in C57BL6/J mice before and after drug exposure. This approach provides a high-fidelity screen of taste thresholds and allows for individual mice to be tracked before and after drug exposure.

Keywords

Taste; Salt; ENaC; Cocaine; Nicotine; Gustation

Available for download on Thursday, November 26, 2020

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