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Abstract The peripheral taste system is more complex than previously thought. The novel taste-signaling proteins TRPM4 and PLCβ3 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 (PLCβ3 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. PLCβ3 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. 

Our lab previously established that repeated exposure to a bitter diet can increase salivary protein (SP) expression, which corresponds to an increase in acceptance of the bitter stimulus. However, this work was exclusively in male rodents, here we examine sex differences. We found that there are no differences in SP expression (experiment 1) or quinine diet acceptance (experiment 2) across stage of estrous cycle. Yet, males and females differ in feeding behaviors, SP expression, and responses to a quinine diet (experiment 3). On a quinine diet, males accepted the diet much faster than females. Males displayed a compensatory increase in meal number as meal size and rate of feeding decreased with initial exposure to a quinine diet, whereas females decreased meal size and rate of feeding with no compensation in meal number. There were sex differences in SP expression at day 14 of quinine exposure but these were gone by day 24. Both sexes increased acceptance of quinine in a brief access taste test after the feeding trial concluded. These data suggest that males and females have different patterns of bitter diet acceptance, but extended exposure to quinine diet still results in altered bitter taste responding and changes in SP profiles in females. 

A subset of salivary proteins (SPs) upregulates in response to a quinine-containing diet. The presence of these SPs then results in decreased bitter taste responding and taste nerve signaling. Bitter taste receptors in the oral cavity are also found in the stomach and intestines and contribute to behaviors that are influenced by post-oral signaling. It has been previously demonstrated that after several pairings of post-orally infused bitter stimuli and a neutral flavor, animals learn to avoid the flavor that was paired with gastric bitter, this is referred to as conditioned avoidance. Furthermore, animals will decrease licking of a neutral solution within a test session, when licking is paired with an intragastric bitter infusion; this has been described as within-session suppression. We used these paradigms to test the role of SPs in behaviors influenced by post-oral signaling. In both paradigms, the animal is given a test solution directly into the stomach (with or without quinine, and with or without SPs), and the infusions are self-administered by licking to a neutral solution (Kool-Aid). Quinine successfully conditioned a flavor avoidance, but, in a separate trial, we were unable to detect conditioning in the presence of SPs from donor animals. Likewise, quinine was able to suppress licking within the conditioned suppression paradigm, but the effect of the bitter was blocked in the presence of saliva containing SPs. Together, these data suggest that behaviors driven by post-oral signaling can be altered by SPs.