Explore the vast range of titles available.

Animal models suggest that sucrose activates taste afferents differently than non-caloric sweeteners. Little information exists how artificial sweeteners engage central taste pathways in the human brain. We assessed sucrose and sucralose taste pleasantness across a concentration gradient in 12 healthy control women and applied 10% sucrose and matched sucralose during functional magnet resonance imaging. The results indicate that (1) both sucrose and sucralose activate functionally connected primary taste pathways; (2) taste pleasantness predicts left insula response; (3) sucrose elicits a stronger brain response in the anterior insula, frontal operculum, striatum and anterior cingulate, compared to sucralose; (4) only sucrose, but not sucralose, stimulation engages dopaminergic midbrain areas in relation to the behavioral pleasantness response. Thus, brain response distinguishes the caloric from the non-caloric sweetener, although the conscious mind could not. This could have important implications on how effective artificial sweeteners are in their ability to substitute sugar intake.

Key Points Taste buds are composed of two excitable cell types and a glia-like cell; each type of cell has distinct functions. Basic taste qualities are detected by G protein-coupled type 1 and type 2 taste receptors, by other receptors and ion channels, and possibly by transporters. ATP is an afferent taste transmitter and is secreted by taste bud cells through an unconventional, non-vesicular release mechanism. ATP, serotonin and GABA mediate cell–cell interactions in the taste bud that may shape transmission to sensory afferent fibres. Controversy remains regarding whether peripheral taste coding follows a labelled-line or combinatorial pattern. Taste preferences and appetites seem to have a genetic component that is being revealed by molecular and population studies. Mammals detect the nutrient content, palatability and potential toxicity of food through taste buds that are present mainly in the tongue. In this Review, Roper and Chaudhari discuss the taste bud cells, receptors and transmitters that are involved in taste detection, how these cells communicate with sensory afferent fibres, and peripheral taste coding. The past decade has witnessed a consolidation and refinement of the extraordinary progress made in taste research. This Review describes recent advances in our understanding of taste receptors, taste buds, and the connections between taste buds and sensory afferent fibres. The article discusses new findings regarding the cellular mechanisms for detecting tastes, new data on the transmitters involved in taste processing and new studies that address longstanding arguments about taste coding.

The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor molecules and associated components for downstream signal transduction cascades. Recent years have witnessed major advances in our understanding of the molecular mechanisms underlying transduction of basic tastes in taste buds, including the identification of the bona fide sour sensor H+ channel OTOP1, and elucidation of transduction of the amiloride-sensitive component of salty taste (the taste of sodium) and the TAS1R-independent component of sweet taste (the taste of sugar). Studies have also discovered an unconventional chemical synapse termed “channel synapse” which employs an action potential-activated CALHM1/3 ion channel instead of exocytosis of synaptic vesicles as the conduit for neurotransmitter release that links taste cells to afferent neurons. New images of the channel synapse and determinations of the structures of CALHM channels have provided structural and functional insights into this unique synapse. In this review, we discuss the current view of taste transduction and neurotransmission with emphasis on recent advances in the field.

Much of what we learned in school about how we taste is wrong. Progress in understanding how taste works is providing insights that may help in the management of obesity, diabetes, and other illnesses.

The mammalian tongue contains gustatory receptors tuned to basic taste types, providing an evolutionarily old hedonic compass for what and what not to ingest. Although representation of these distinct taste types is a defining feature of primary gustatory cortex in other animals, their identification has remained elusive in humans, leaving the demarcation of human gustatory cortex unclear. Here we used distributed multivoxel activity patterns to identify regions with patterns of activity differentially sensitive to sweet, salty, bitter, and sour taste qualities. These were found in the insula and overlying operculum, with regions in the anterior and middle insula discriminating all tastes and representing their combinatorial coding. These findings replicated at super-high 7 T field strength using different compounds of sweet and bitter taste types, suggesting taste sensation specificity rather than chemical or receptor specificity. Our results provide evidence of the human gustatory cortex in the insula. Previous research shows how taste types are represented across regions of the brain in non-human animals. Here, the authors examine how four basic tastes are represented in the human brain, showing evidence of the human gustatory cortex in the insula.

The turnover and re-establishment of peripheral taste synapses is vital to maintain connectivity between primary taste receptor cells and the gustatory neurons which relay taste information from the tongue to the brain. Despite the importance of neuron-taste cell reconnection, the mechanisms governing synapse assembly in the taste bud are largely unknown. To determine whether nerve fiber connectivity is an initiating factor for the recruitment of presynaptic machinery in taste receptor cells, we use the expression of CALHM1 and Bassoon to identify presynaptic sites in type II (sweet, umami, bitter) and type III (sour) taste receptor cells, respectively. Under homeostatic conditions, the vast majority (>90%) of presynaptic sites are directly adjacent to nerve fibers (contacted). In the days immediately following gustatory nerve transection and denervation of taste buds, Bassoon and CALHM1 puncta are markedly reduced. This suggests that nerve fiber innervation is crucial for the recruitment and maintenance of presynaptic sites. During nerve fiber regeneration into the taste bud, presynaptic sites begin to replenish but are not as frequently contacted by nerve fibers as intact controls (35–54% compared to >90%). This reveals that taste cells rely on gustatory fiber innervation to organize presynaptic sites. Additionally, our finding that presynaptic sites are not as frequently contacted by regenerating axons suggests a model whereby trophic factors secreted by gustatory nerve fibers prompt taste receptor cells to produce and/or aggregate presynaptic specializations at the cell membrane prior to contact. This, in turn, may guide neurons to form mature synapses. These findings provide new insights into the mechanisms driving synaptogenesis and synaptic plasticity within the rapidly changing taste bud environment.

Ammonium (NH 4 + ), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH 4 Cl). Extracellular NH 4 Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH 4 Cl relative to acid stimuli. Taste responses to NH 4 Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1 −/− mouse strain. Behavioral aversion of mice to NH 4 Cl, reduced in Skn-1a −/− mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1 . These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH 4 Cl and a previously undescribed channel activation mechanism. Ammonium is detected by chemosensory systems of humans and other animals to guide avoidance or attractive behavior. Here, the authors show that the proton channel OTOP1 is activated by ammonium, is required for ammonium taste responses in mice, and identify a conserved residue involved in ammonium sensitivity.

Receptors for bitter, sugar, and other tastes have been identified in the fruit fly Drosophila melanogaster, while a broadly tuned receptor for the taste of acid has been elusive. Previous work showed that such a receptor was unlikely to be encoded by a gene within one of the two major families of taste receptors in Drosophila, the “gustatory receptors” and “ionotropic receptors.” Here, to identify the acid taste receptor, we tested the contributions of genes encoding proteins distantly related to the mammalian Otopertrin1 (OTOP1) proton channel that functions as a sour receptor in mice. RNA interference (RNAi) knockdown or mutation by CRISPR/Cas9 of one of the genes, Otopetrin-Like A (OtopLA), but not of the others (OtopLB or OtopLC) severely impaired the behavioral rejection to a sweet solution laced with high levels of HCl or carboxylic acids and greatly reduced acid-induced action potentials measured from taste hairs. An isoform of OtopLA that we isolated from the proboscis was sufficient to restore behavioral sensitivity and acid-induced action potential firing in OtopLA mutant flies. At lower concentrations, HCl was attractive to the flies, and this attraction was abolished in the OtopLA mutant. Cell type–specific rescue experiments showed that OtopLA functions in distinct subsets of gustatory receptor neurons for repulsion and attraction to high and low levels of protons, respectively. This work highlights a functional conservation of a sensory receptor in flies and mammals and shows that the same receptor can function in both appetitive and repulsive behaviors.

Taste stem/progenitor cells from posterior mouse tongues have been used to generate taste bud organoids. However, the inaccessible location of taste receptor cells is observed in conventional organoids. In this study, we established a suspension-culture method to fine-tune taste bud organoids by apicobasal polarity alteration to form the accessible localization of taste receptor cells. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells enabled the direct application of calcium imaging to evaluate the taste response. Moreover, suspension-cultured organoids can be genetically altered. Suspension-cultured taste bud organoids harmoniously integrated with the recipient lingual epithelium, maintaining the taste receptor cells and gustatory innervation capacity. We propose that suspension-cultured organoids may provide an efficient model for taste research, including taste bud development, regeneration, and transplantation.

Salt to taste Mammals are repelled by large concentrations of salts but attracted to low concentrations of sodium. In mice, the latter behaviour can be blocked by the ion-channel inhibitor amiloride. Now mice genetically engineered to lack the drug's target sodium channel, ENaC, in taste receptor neurons have been found to lack both salt sensing and sodium taste responses. Thus sodium sensing, like the four other taste modalities (sweet, sour, bitter and umami), is mediated by dedicated taste-receptor cells. Though because sodium sensing is amiloride-insensitive in primates, how this relates to our ability to taste salt remains unclear. Mammals are repelled by large concentrations of salts but attracted to low concentrations of sodium. In mice, the latter behaviour can be blocked by the ion channel inhibitor amiloride. Here, mice have been produced lacking the drug's target sodium channel, ENaC, specifically in taste receptor neurons. It is confirmed that sodium sensing, like the four other taste modalities (sweet, sour, bitter and umami), is mediated by a dedicated 'labelled line'. Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion 1 , 2 , 3 , 4 , 5 . Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts 1 , 2 , 3 , 6 , 7 , 8 , 9 . Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system 1 , 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 . Previously, we showed that four of the five basic taste qualities—sweet, sour, bitter and umami—are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses 5 , 15 , 16 , 17 , 18 . Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC 19 , 20 , and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCα in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.