Sensory end-organs vary in their cellular and functional complexity. In taste buds, mature cells display diverse properties. A rational system of classification of taste cell types has begun to inform us how information flows through the taste bud, and the roles of different cells in generating an integral taste signal. While Receptor (Type II) cells have been investigated at length, we still know relatively little about the neuron-like Presynaptic (Type III) cells, and even less about the most abundant cells: the Type I cells. Based on our preliminary studies, we hypothesize that Type I cells, perform essential glial functions including regulating the ionic environment, and interacting with Receptor and Presynaptic cells via chemical signals. Further, because Presynaptic taste cells display many characteristics of neurons, we hypothesize that they are significantly longer-lived than other cells in the taste bud. We will test specific hypotheses regarding the less-understood, but prevalent Type I and III cells to develop a better integrated picture of how the taste bud functions as a whole. Specifically, we will: 1. Test the hypothesis that Type I taste cells regulate the extracellular ionic environment within the taste bud through the action of several ion channels, pumps and transporters. For this, we will use single-cell gene expression profiling, immunohistochemistry, confocal Ca2+ imaging of intact taste buds and briefaccess behavioral tests to evaluate the involvement of specific candidate ion channels. 2. Test the hypothesis that Type I taste cells use GABA as a gliotransmitter to modulate taste signaling. For this, we will use a unique transgenic mouse with Type I cells fluorescently labeled, in combination with single-cell expression profiling and confocal Ca2+ imaging of intact taste buds. We will look for downstream consequences of GABA signaling such as modulation of tastant-evoked responses. 3. Test the hypothesis that Presynaptic taste cells, the most neuron-like in the taste bud, have the greatest longevity. For this, we will employ a new technology, labeling with 5-ethynyl-2 -deoxyuridine (EdU), on mice with transgenically marked cell types. Our preliminary data show remarkable cellular resolution with this new method. In addition to defining taste cell dynamics, measurements of cell typespecific lifespans will also help to clarify lineage relationships of cells in the taste bud. Much as resurgent interest in glia is revealing their numerous essential functions in the CNS, our analyses will reveal interactions of two less-studied cell types, and their roles in the biology of taste buds.
Taste buds detect nutritive and potentially poisonous materials through the coordinated action of distinct types of cells housed in taste buds throughout the oral cavity. We will investigate how cells located in taste buds, but resembling glia, may influence the sensitivity of taste buds. Because the proteins responsible for regulation are in an accessible location, understanding these mechanisms introduces the possibility of pharmacological manipulation of aversive and appetitive taste sensations.
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