Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala

The responses of 3687 neurons in the macaque primary taste cortex in the insula/frontal operculum, orbitofrontal cortex (OFC) and amygdala to oral sensory stimuli reveals principles of representation in these areas. Information about the taste, texture of what is in the mouth (viscosity, fat texture and grittiness, which reflect somatosensory inputs), temperature and capsaicin is represented in all three areas. In the primary taste cortex, taste and viscosity are more likely to activate different neurons, with more convergence onto single neurons particularly in the OFC and amygdala. The different responses of different OFC neurons to different combinations of these oral sensory stimuli potentially provides a basis for different behavioral responses. Consistently, the mean correlations between the representations of the different stimuli provided by the population of OFC neurons were lower (0.71) than for the insula (0.81) and amygdala (0.89). Further, the encoding was more sparse in the OFC (0.67) than in the insula (0.74) and amygdala (0.79). The insular neurons did not respond to olfactory and visual stimuli, with convergence occurring in the OFC and amygdala. Human psychophysics showed that the sensory spaces revealed by multidimensional scaling were similar to those provided by the neurons.     

Responsiveness of the cortical taste area neurons to a mixture of the four basic tastants in rats

The taste coding mechanism in the cortical taste area was investigated by analyzing the responses of 59 neurons in the cortical taste area of the anesthetized rat to a mixture of the four basic tastants in both absence and presence of bicuculline methiodide, a specific antagonist to the GABA(A) receptors. The mixture caused response suppression more frequently than response facilitation, both in the control state and during bicuculline application. Cluster analysis revealed that only a group of the neurons with the best response to both NaCl and HCl (group NH) showed the best response to the mixture in the control state, whereas during bicuculline application, in addition to group NH, two other groups of neurons responding to sucrose, or to HCl and quinine responded vigorously to the mixture. Multidimensional scaling located the mixture outside the space of the four basic tastants facing an NaCl-HCl line in both states. GABAergic inhibition caused the group NH to represent the taste of the mixture in the control state. Thus, the mixture probably tastes salty and sour to rats. No cortical neuron was found which specifically responded to the mixture.     

Molecular signaling during taste aversion learning

Behavioral and neural assessment tools have been used to identify cellular and molecular events that occur during taste aversion acquisition. Studies described here include an assessment of taste information processing and taste-illness association using fos-like immunoreactivity (FLI) to mark populations of cells that react strongly to the taste conditioned stimulus (CS), the illness unconditioned stimulus (US), or the pairing of CS and US. Exposure to a novel, but not a familiar, CS taste (saccharin) was found to induce robust increases in FLI in some, but not all, brain regions previously implicated in taste processing or taste aversion learning. Striking effects of taste novelty on FLI were found in central amygdala (CNA) and insular cortex (IC) but not in basolateral amygdala (BLA), pontine parabrachial nucleus (PBN), or nucleus of the solitary tract (NTS). Of those regions responding to taste novelty, only CNA showed significant elevations in FLI in response to the US, LiCl. In additional studies, FLI was examined after an effective training experience, novel CS-US pairing, and compared with an ineffective one, familiar CS-US pairing. After CS-US pairing, taste novelty modulated FLI in virtually all the regions previously implicated in conditioned taste aversion (CTA) learning, including PBN, CNA, BLA, IC, as well as NTS. Thus, a distributed and interdependent neural CTA circuit is mapped using this method, and the use of localized lesion and inactivation studies promises to further define the functional role of structures within this circuit.     

Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala drives aversive taste memory retrieval

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Molecular mechanisms underlying the reception and transmission of sour taste information

Taste enables organisms to determine the properties of ingested substances by conveying information regarding the five basic taste modalities: sweet, salty, sour, bitter, and umami. The sweet, salty, and umami taste modalities convey the carbohydrate, electrolyte, and glutamate content of food, indicating its desirability and stimulating appetitive responses. The sour and bitter modalities convey the acidity of food and the presence of potential toxins, respectively, stimulating aversive responses to such tastes. In recent years, the receptors mediating sweet, bitter, and umami tastes have been identified as members of the T1R and T2R G-protein-coupled receptor families; however, the molecular mechanisms underlying sour taste detection have yet to be clearly elucidated. This review covers the molecular mechanisms proposed to mediate the detection and transmission of sour stimuli, focusing on polycystic kidney disease 1-like 3 (Pkd1l3), Pkd2l1, and carbonic anhydrase 4 (Car4).     

Variation of Hexose 1-P Uridylyltransferase and UDP-Gal Pyrophosphorylase in Bifidobacterium bifidum Culture

Taste is indispensable for vertebrate to find a proper way of living by selection of foods at their discretion. It is also a mainstay in the construction of human culture and the food industry, but no systematic information is available regarding the molecular logic of taste signaling and associated chemical entities. Against this backdrop, our research had bumble beginnings in the 1990s and then traced a unique path of development revealing major signaling pathways involving G protein-coupled receptors, Gαi2, PLC-β2, IP₃R3, PLA2IIa, TRPM5, KCNQ1, etc. The validity of our studies on the molecular biology of taste was verified by material science in the case of an enigmatic protein, neoculin, which converts sourness to sweetness. The study should provide new information for better understanding of taste-taste interactions which are important in food design.     

Laterality of human primary gustatory cortex studied by MEG

We examined the laterality of the human gustatory neural pathway by measuring gustatory-evoked magnetic fields (GEMfs) and demonstrating the activation of the human primary gustatory cortex (PGC). In patients whose chorda tympani nerve had been severed unilaterally on the right side, we stimulated the normal side (i.e., left side) of the chorda tympani nerve with NaCl solution using a device developed for measuring GEMfs. We used the whole-head magnetoencephalography system for recording GEMfs and analyzed the frequency and latency of PGC activation in each hemisphere. "The transitional cortex between the insula and the parietal operculum" was identified as PGC with the base of the central sulcus in this experiment. Significant difference was found in frequencies among bilateral, only-ipsilateral, and only-contralateral responses by the Friedman test (P < 0.05), and more frequent bilateral responses were observed than only-ipsilateral (P < 0.05) or only-contralateral responses (P < 0.01) by the multiple comparison tests. In the bilateral responses, the averaged activation latencies of the transitional cortex between the insula and the parietal operculum were not significantly different in both hemispheres. These results suggest that unilateral gustatory stimulation will activate the transitional cortex between the insula and the parietal operculum bilaterally in humans.     

Top-Down Control of Sweet and Bitter Taste in the Mammalian Brain

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A psychophysical investigation of binary bitter-compound interactions

The aim of this study was to determine if taste interactions occur when bitter stimuli are mixed. Eight bitter stimuli were employed: denatonium benzoate (DB), quinine-HCl (QHCl), sucrose octaacetate (SOA), urea, L-tryptophan (L-trp), L-phenylalanine (L-phe), ranitidine-HCl, and Tetralone. The first experiment constructed individual psychophysical curves for each subject (n = 19) for each compound to account for individual differences in sensitivities when presenting bitter compounds in experiment 2. Correlation analysis revealed two groupings of bitter compounds at low intensity (1, L-trp, L-phe, and ranitidine; 2, SOA and QHCl), but the correlations within each group decreased as the perceived intensity increased. In experiment 2, intensity ratings and two-alternative forced-choice discrimination tasks showed that bitter compounds generally combine additively in mixture and do not show interactions with a few specific exceptions. The methods employed detected synergy among sweeteners, but could not detect synergy among these eight bitter compounds. In general, the perceived bitterness of these binary bitter-compound mixtures was an additive function of the total bitter-inducing stimuli in the mouth.     

Chemical stimulation of the thalamic reticular nucleus inhibits the neuronal activity of the posterior insular cortex in rats

Extracellular neuronal responses were recorded from the posterior insular cortex following electrical and chemical stimulation of the thalamic reticular nucleus (Rt) regions. In the present study, most neurons (29/32) were first characterized for their responses to electrical stimulation of the superior laryngeal (SL) nerve or glossopharyngeal (IXth) nerve. In the first experiment, 15 neurons in the posterior insular cortex were examined for their responses to electrical stimulation of the Rt regions. It was found that effective stimulation sites to evoke action potentials in the posterior insular cortex were the ventromedial portion of the Rt and its adjacent regions. In the second experiment, 17 neurons in the posterior insular cortex were examined for their responses by pressure injection of glutamate (Glu) into the Rt regions. Of the 17 neurons, 13 were inhibited in the spontaneous discharge rate following injection of Glu into the Rt, and the remaining four were unaffected. Histologically, it was demonstrated that Glu injection sites for the case of inhibition were located near or within the Rt. On the other hand, the injection sites for all four non-responsive neurons were located outside of the Rt. These data suggest that excitation of the Rt (GABAergic neurons) causes depression of the neuronal activity in the thalamic relay nucleus and then this may in turn induce depressed neuronal activity in the posterior insular cortex. The results here indicate that neuronal activity in the posterior insular cortex is controlled by the Rt, which has been reported in other sensory systems.     

The taste system in fishes and the effects of environmental variables

The adaptability of the taste system in fish has led to a large variety in taste bud morphology, abundance and distribution, as well as in taste physiology characteristics in closely related species with different modes of life and feeding ecology. However, the modifications evoked in the sense of taste, or gustation, particularly during ontogeny when fishes are subject to different environmental variables, remain poorly studied. This review paper focusses on current knowledge to show how plastic and resistant the taste system in fishes is to various external factors, linked to other sensory inputs and shifts in physiological state of individuals. Ambient water temperature is fundamental to many aspects of fish biology and taste preferences are stable to many substances, however, the taste-cell turnover rate strongly depends on water temperature. Taste preferences are stable within water salinity, which gives rise to the possibility that the taste system in anadromous and catadromous fishes will only change minimally after their migration to a new environment. Food-taste selectivity is linked to fish diet and to individual feeding experience as well as the motivation to feed evoked by attractive (water extracts of food) and repellent (alarm pheromone) odours. In contrast, starvation leads to loss of aversion to many deterrent substances, which explains the consumption by starving fishes of new objects, previously refused or just occasionally consumed. Food hardness can significantly modify the final feeding decision to swallow or to reject a grasped and highly palatable food item. Heavy metals, detergents, aromatic hydrocarbons and other water contaminants have the strongest and quickest negative effects on structure and function of taste system in fish and depress taste perception and ability of fishes to respond adequately to taste stimuli after short exposures. Owing to phenotypic plasticity, the taste system can proliferate and partially restore the ability of fishes to respond to food odour after a complete loss of olfaction. In general, the taste system, especially its functionality, is regarded as stable over the life of a fish despite any alteration in their environment and such resistance is vital for maintaining physiological homeostasis.     

Modulation of rat chorda tympani NaCl responses and intracellular Na+ activity in polarized taste receptor cells by pH

Mixture interactions between sour and salt taste modalities were investigated in rats by direct measurement of intracellular pH (pH(i)) and Na(+) activity ([Na(+)](i)) in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) nerve recordings. Stimulating the lingual surface with NaCl solutions adjusted to pHs ranging between 2.0 and 10.3 increased the magnitude of NaCl CT responses linearly with increasing external pH (pH(o)). At pH 7.0, the epithelial sodium channel (ENaC) blocker, benzamil, decreased NaCl CT responses and inhibited further changes in CT responses induced by varying pH(o) to 2.0 or 10.3. At constant pH(o), buffering NaCl solutions with potassium acetate/acetic acid (KA/AA) or HCO(3)(-)/CO(2) inhibited NaCl CT responses relative to CT responses obtained with NaCl solutions buffered with HEPES. The carbonic anhydrase blockers, MK-507 and MK-417, attenuated the inhibition of NaCl CT responses in HCO(3)(-)/CO(2) buffer, suggesting a regulatory role for pH(i). In polarized TRCs step changes in apical pH(o) from 10.3 to 2.0 induced a linear decrease in pH(i) that remained within the physiological range (slope = 0.035; r(2) = 0.98). At constant pH(o), perfusing the apical membrane with Ringer's solutions buffered with KA/AA or HCO(3)(-)/CO(2) decreased resting TRC pH(i), and MK-507 or MK-417 attenuated the decrease in pH(i) in TRCs perfused with HCO(3)(-)/CO(2) buffer. In parallel experiments, TRC [Na(+)](i) decreased with (a) a decrease in apical pH, (b) exposing the apical membrane to amiloride or benzamil, (c) removal of apical Na(+), and (d) acid loading the cells with NH(4)Cl or sodium acetate at constant pH(o). Diethylpyrocarbonate and Zn(2+), modification reagents for histidine residues in proteins, attenuated the CO(2)-induced inhibition of NaCl CT responses and the pH(i)-induced inhibition of apical Na(+) influx in TRCs. We conclude that TRC pH(i) regulates Na(+)-influx through amiloride-sensitive apical ENaCs and hence modulates NaCl CT responses in acid/salt mixtures.     

Fat taste in humans: Sources of within- and between-subject variability

Non-esterified fatty acids (NEFA) are reportedly detectable through taste mechanisms in the human oral cavity. However, wide variability has been observed in NEFA taste sensitivity between and within subjects as well as across research groups. Some of this variability may be due to the hydrophobic nature of the NEFA and the methods used to make stimuli emulsions. As NEFA are poorly soluble in water, emulsification is necessary for delivery of stimuli to taste receptors. However, properties of emulsions may also be detected by somatosensory cues complicating attribution of sensory findings to taste. Additionally, learning (improved test performance) has been observed when using traditional tests for measuring sensitivity to NEFA, which may contribute greatly to within-subject variability if not standardized. Factors such as sex, diet, and BMI have been proposed to affect NEFA taste sensitivity, but the degree to which these individual factors influence NEFA detection thresholds remains to be fully established. Improved knowledge of stimulus properties and individual sensory capabilities will be needed to further evaluate the posited taste component to human oral fat detection. Progress in this area should facilitate the translation of findings on how NEFA taste may contribute to or reflect food choice and chronic disease risk.     

Metallic taste from electrical and chemical stimulation

A series of three experiments investigated the nature of metallictaste reports after stimulation with solutions of metal saltsand after stimulation with metals and electric currents. Tostimulate with electricity, a device was fabricated consistingof a small battery affixed to a plastic handle with the anodeside exposed for placement on the tongue or oral tissues. Intensityof taste from metals and batteries was dependent upon the voltageand was more robust in areas dense in fungiform papillae. Metallictaste was reported from stimulation with ferrous sulfate solutions,from metals and from electric stimuli. However, reports of metallictaste were more frequent when the word ‘metallic’was presented embedded in a list of choices, as opposed to simplefree-choice labeling. Intensity decreased for ferrous sulfatewhen the nose was occluded, consistent with a decrease in retronasalsmell, as previously reported. Intensity of taste evoked bycopper metal, bimetallic stimuli (zinc/copper) or small batteries(1.5–3 V) was not affected by nasal occlusion. This differencesuggests two distinct mechanisms for evocation of metallic tastereports, one dependent upon retronasal smell and a second mediatedby oral chemoreceptors.     

(+)-(S)-alapyridaine--a general taste enhancer?

N-(1-Carboxyethyl)-6-hydroxymethyl-pyridinium-3-ol inner salt (alapyridaine), recently identified in heated sugar/amino acid mixtures as well as in beef bouillon, has been shown to exhibit general taste-enhancing activities, although tasteless on its own. Differing from other taste enhancers reported so far, racemic (R/S)-alapyridaine and, to an even greater extent (+)-(S)-alapyridaine, the physiologically active enantiomer, are able to enhance more than one basic taste quality. The threshold concentrations for the sweet taste of glucose and sucrose, for the umami taste of monosodium L-glutamate (MSG) and guanosine-5'-monophosphate (GMP), as well as the salty taste of NaCl, were significantly decreased when alapyridaine was present. In contrast, perception of the bitter tastes of caffeine and L-phenylalanine, as well as of sour-tasting citric acid, was unaffected. Furthermore, alapyridaine was shown to intensify known taste synergies such as, for example, the enhancing effect of L-arginine on the salty taste of NaCl, as well as that of GMP on the umami taste of MSG. The activity of (+)-(S)-alapyridaine could be observed not only in solutions of single taste compounds, but also in more complex tastant mixtures; for example, the umami, sweet and salty taste of a solution containing MSG, sucrose, NaCl and caffeine was significantly modulated, thus indicating that alapyridaine is a general taste enhancer.