TRPM4 and PLCß3 contribute to normal behavioral responses to an array of sweeteners and carbohydrates but PLCß3 is not needed for taste-driven licking for glucose.

The peripheral taste system is more complex than previously thought. The novel taste-signaling proteins TRPM4 and PLCß3 appear to function in normal taste responding as part of Type II taste cell signaling or as part of a broadly responsive (BR) taste cell that can respond to some or all classes of tastants. This work begins to disentangle the roles of intracellular components found in Type II taste cells (TRPM5, TRPM4, and IP3R3) or the BR taste cells (PLCß3 and TRPM4) in driving behavioral responses to various saccharides and other sweeteners in brief-access taste tests. We found that TRPM4, TRPM5, TRPM4/5, and IP3R3 knockout (KO) mice show blunted or abolished responding to all stimuli compared with wild-type. IP3R3 KO mice did, however, lick more for glucose than fructose following extensive experience with the 2 sugars. PLCß3 KO mice were largely unresponsive to all stimuli except they showed normal concentration-dependent responding to glucose. The results show that key intracellular signaling proteins associated with Type II and BR taste cells are mutually required for taste-driven responses to a wide range of sweet and carbohydrate stimuli, except glucose. This confirms and extends a previous finding demonstrating that Type II and BR cells are both necessary for taste-driven licking to sucrose. Glucose appears to engage unique intracellular taste-signaling mechanisms, which remain to be fully elucidated.

Dietary experience with glucose and fructose fosters heightened avidity for glucose-containing sugars independent of TRPM5 taste transduction in mice.

OBJECTIVE: Experience with metabolically distinct sugars, glucose and fructose, enhances attraction to the orosensory properties of glucose over fructose. To gain insight into which sensory signals are affected, we investigated how this nutritive learning reshapes behavioral responding to various sugars in brief access taste tests in C57BL6/J (B6) mice and assessed whether sugar-exposed mice lacking the TRPM5 channel involved in G-protein coupled taste transduction could acquire these types of preferences for glucose-containing sugars. METHODS: B6, TRPM5 knockout (KO), and TRPM5 heterozygous (Het) mice were given extensive access to water (sugar naïve) or 0.316, 0.56, and 1.1 M glucose and fructose (sugar-exposed) and then tested, whilst food deprived, for their relative avidities for glucose, fructose, sucrose, maltose, and/or a non-metabolizable glucose analog in a series of taste tests. RESULTS: Sugar-exposed B6 mice licked relatively more for glucose than fructose, driven by an increased avidity for glucose, not an avoidance of fructose, and licked more for maltose, compared to their sugar-naïve counterparts. Sugar-exposed B6 mice did not lick with such avidity for a non-metabolizable glucose analog. TRPM5 KO mice took longer to acquire the sugar discrimination than the Het controls, but both groups ultimately licked significantly more for glucose than fructose. Het mice displayed clear preferential licking for sucrose over fructose, while licking comparably high for glucose, sucrose, and maltose. KO mice licked significantly more for maltose than sucrose. CONCLUSIONS: Collectively, the findings suggest that ingestive experience with glucose and fructose primarily reprograms behavioral responding to a TRPM5-independent orosensory signal generated by glucose-containing sugars.