| 2009 — 2011 |
Breza, Joseph Michael |
F31Activity Code Description:
To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Modulation of Peripheral Gustatory Neurons by Organic Salts and Organic Acids @ Florida State University
DESCRIPTION (provided by applicant): Taste is a critical sensory system which acts as an instrument, in the detection, recognition, and ultimately ingestion of sodium (Na+), a necessary nutrient indispensable to life. NaCI, the prototypical salt stimulus, is used as a food preservative and additive to increase the flavor of foods and has been so since the beginning of recorded history. Today however, many preservatives in the form of organic Na+ salts, with large anions and organic acids are used in processed foods to increase shelf life, maintain color, and prevent caking, etc. The effect of these additives is generally a decrease in the overall perceived saltiness. Hence, more Na+ is added to processed foods in order to achieve the same saltiness, which results in over consumption of Na+, possibly leading to development of hypertension, an American epidemic. Supporting evidence from electrophysiological chorda tympani nerve recordings have shown that organic Na+ salts with large anions as well as acidic sodium salt solutions, reduce the chorda tympani nerve response. Surprisingly however, these experiments have not been examined on a single neuron level, leaving coding mechanisms of Na+ taste largely unknown. Moreover, a critical variable in cracking neural codes for any sensory system is knowing when the stimulus reaches the receptors and the taste field lacks this stimulus resolution leaving unique firing patterns such as stimulus-evoked inhibition, on-off, lateral-inhibition, etc unknown. Accordingly, (with the help of a colleague) developed the Electrogustogram (EGG) in order to investigate the precise moment of stimulus application while simultaneously recording from single neurons in the rat geniculate ganglion for several hours, thereby providing detailed analyses of neuron response profiles. The following experiments are designed to examine the effects of anion size and acidity on Na+ taste by single unit neurophysiology in the rat geniculate ganglion. The role of the epithelial sodium channel (ENaC) and the transient receptor potential vanilloid receptor 1 (TRPV1) in Na+ responses will be determined using benzamil and SB366791, specific ENaC and TRPV1 antagonists, respectively. Specific aim 1 will characterize the salt response profiles from 3 monosodium salts that vary in anion size, and to KCI, each at 4 concentrations, and the effect of acidity on these salt responses. Acidic foods are thought to decrease the overall saltiness of food, by decreasing the conductance of Na+ though ENaC via intracellular acidification. Thus, Specific aim 2 will evaluate Na+ responses from gustatory neuron types in the presence of organic acids at acidic and at a neutral pH. PUBLIC HEALTH RELEVANCE: Understanding the peripheral gustatory coding mechanisms of Na+ can provide insight into the over-consumption of Na+ via processed foods.
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| 2018 — 2020 |
Breza, Joseph Michael |
R21Activity Code Description:
To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Lightly Salted: An Optogenetic Approach to Uncover the Role of Type I Cells in Salt Taste Transduction @ Eastern Michigan University
Sodium (Na+) is an essential nutrient, but humans consume this nutrient in excess which increases the risk of hypertension and stroke. It is currently unknown which cell type within taste buds is responsible for Na+-taste transduction. Here, an optogenetic approach is used to determine whether Type I cells within taste buds are responsible for Na+ taste transduced through epithelial sodium channels (ENaCs). Optogenetic manipulation of Type I taste-bud cells allows for selective perturbation of taste-bud circuity with an unprecedented level of precision? unmatched by conventional pharmacology?and serves as a valuable tool for unraveling the enigma of the taste of Na+. This project will test two hypotheses. 1) Optogenetic activation (via Channelrhodopsin-2; ChR2) of Type I cells in fungiform-taste buds activates NaCl-best neurons in the mouse Nucleus Tractus Solitarius (NTS), located in the medulla. 2) Optogenetic activation (via ChR2) of Type I cells in fungiform taste buds elicits Na+ taste and drives Na+ appetite in Na+ deprived mice. Knowledge obtained from these investigations will provide the field with much needed information about the role of Type I cells in taste function, and could provide a target for pharmacological manipulation of taste circuitry to enhance salt taste, thereby decreasing Na+ intake. Such discoveries would have a positive impact on human health and disease afflicted by excess Na+ consumption.
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