Saturday, November 23, 2024
11/23/2024
Project Summary Flavor is associated with food selection and preference behaviors in humans. Flavor is contributed by taste, olfaction, and somatosensory sensations such as food temperature. During food sampling, cooling sensations frequently accompany taste experiences in the mouth due to the high resting temperature of intraoral skin. Yet compared to taste biology, there are wide, significant gaps in our understanding of how temperature sensing impacts ingestive preferences and behavior. A goal of the proposed studies is to begin to define how thermal sensations and receptor mechanisms participate in orosensory-guided preference and ingestive responses in mice. This is a mostly unexplored area of study critical to flavor neurobiology. For behavioral tests, we have engineered an adapter that independently varies the temperatures of fluids inside multiple sipper tubes presented individually to mice by a lickometer. When coupled with this adapter, the lickometer can perform brief-access fluid licking tests that gauge how oral temperature sensations influence sensory/tongue control of mouse licking behavior. Using our thermo-lickometer, Aim 1 will study how thermal sensations mediated by the transient receptor potential (TRP) melastatin 8 (TRPM8) cold receptor found on trigeminal fibers contribute to orobehavioral responses to cooling temperatures. To do this, we will evaluate if mice gene-deficient for TRPM8 show impaired innate and conditioned licking responses to chilled water compared to wild-type. Studies will ask if TRPM8 input is necessary for mice to behaviorally separate oral cooling sensations from warm temperatures that our pilot data show are avoided when sensed in the mouth. Aim 2 will study how oral thermal sensing by TRPM8 impacts taste preferences. We will gauge if cooling temperatures that excite TRPM8 complement and counter preference and avoidance of sweet and bitter taste stimuli by comparing brief-access licking to temperature-controlled tastes between control and TRPM8 deficient mice. Aim 3 will measure brief- access licking of temperature-controlled fluids in mice with silenced trigeminal thermosensory afferents or ablation of taste bud cells that express temperature-sensitive receptors. Oral temperature can also excite taste neurons (thermogustation) albeit the function of this has been unknown. Thermosensory afferent mechanisms will be evaluated using mice deficient for TRP vanilloid 1 (TRPV1)-lineage afferents, broadly mediating thermosensation, and mice with conditionally silenced TRPV1-positive trigeminal ganglion neurons, which convey orofacial thermal and nociceptive signals. Thermogustatory mechanisms will be probed using mice deficient for a protein that regulates the development of taste bud cells with temperature-sensitive molecular effectors. Altogether, these studies will provide an initial account of how thermosensory and thermogustatory processes influence ingestive behaviors. Ultimately, defining the role of oral temperature sensing in intake behavior will be critical for understanding causal relationships between flavor and ingestive conditions.
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