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Neural coding mechanisms for flow rate in taste-responsive cells in the nucleus of the solitary tract of the rat.

When a taste stimulus enters the mouth, intentional movement of the stimulus within the oropharyngeal cavity affects the rate at which taste receptors are exposed to the stimulus and may ultimately affect taste perception. Early studies have shown that stimulus flow rate, the experimental equivalent of the effects of these investigative movements, modulates the portion of the peripheral nerve response that occurs when behavioral assessments of tastants are made. The present experiment studied the neural coding mechanisms for flow rate in the nucleus of the solitary tract (NTS), the first central relay in the taste pathway. Responses to NaCl (0.1 M) presented at high (5 ml/s) and low (3 ml/s) flow rates, sucrose (0.5 M), quinine HCl (0.01 M), and HCl (0.01 M) were recorded extracellularly from single NTS units in multiple replications. Information conveyed by evoked responses was analyzed with a family of metrics that quantify the similarity of two spike trains in terms of spike count and spike timing. Information about flow rate was conveyed by spike timing and spike count in approximately equal proportions of units (each approximately 1/3), whereas information about taste quality was conveyed by spike timing in about half of the units. Different subsets of units contributed information for discrimination of flow rate and taste quality.

Animals↗

Neuronal responses of the nucleus tractus solitarius to oral stimulation with umami substances.

In order to investigate coding mechanisms of special taste modality (umami), responses of neurons within the nucleus tractus solitarius (NTS) to oral stimulation with monosodium glutamate, disodium 5'-inosinate (IMP) or their mixture were recorded in the conventional electrophysiological method. Results obtained were as follows: Neither MSG-best nor IMP-best neuron was recorded within the NTS as in the primary taste afferents. Some of the sucrose-best neurons, NaCl-best neurons and HCl-best neurons responded to oral stimulation with MSG or IMP. A remarkable synergistic effect was observed in all of the sucrose-best neurons and in some of the NaCl-best neurons but not in all of the HCl-best neurons, when the mixed solution of MSG and IMP was applied into the oral cavity. As to the sucrose-best neurons, potency of the synergism was positively correlated with the responsiveness to sucrose. No correlation was recognized between them in the case of NaCl-best neurons. These results suggest a view that the sucrose-best neurons and the NaCl-best neurons which show the synergism may participate in coding umami taste.

Afferent Pathways↗

New perspectives on taste and primate evolution: the dichotomy in gustatory coding for perception of beneficent versus noxious substances as supported by correlations among human thresholds.

In various environments where primates are presently observed, as well as in forests and savannas which have been inhabited by australopithecines and early hominids, there are (or there have been presumably) categories of substances eliciting taste signals associated with stereotyped responses. Such is the case for various soluble sugars of fruits and nectars, attracting consumers, and for several plant compounds in which bitter or strongly astringent properties have a repulsive effect. The occurrence of such classes of tasty substances among natural products appears to be related to the evolutionary trends that shaped primate sensory perception (for detecting either beneficent or potentially noxious substances) in the context of a long history of coevolution between animals and plants. Here, we present original psychophysical data on humans (412 individuals aged 17-59 years) as an analogy with which to test recent evidence from electrophysiology in nonhuman primates (Hellekant et al. [1997] J. Neurophysiol. 77:978-993; Danilova et al. [1998] Ann. N.Y. Acad. Sci. 855:160-164) that taste fibers can be grouped into clusters of "best-responding fibers" with two more specific clusters, one for sugars and one for quinine and tannins. The collinearity found between human taste responses (recognition thresholds) for fructose and sucrose, as well as for quinine and tannins, is presented and discussed as another evidence of the two-direction evolutionary trend determining taste sensitivity. Salt perception appears to be totally independent of these trends. Accordingly, the appreciation of a salty taste seems to be a recent culturally learned response, and not a primary taste perception. The very existence of primary tastes is discussed in the context of evolutionary trends, past and present.

Adolescent↗

Coding of gustatory information in the pontine parabrachial nuclei of the rabbit: magnitude of neural response.

An electrophysiological analysis was carried out on 82 neurons in the parabrachial nuclei to study coding of gustatory stimuli. The magnitude of neural discharge evoked by two concentrations of each of 4 basic taste stimuli were subjected to two types of analyses to evaluate neuronal specificity and across-element spatial patterning in the coding of taste quality. Results were compared and contrasted to those in rodents. Profiles of taste response of individual neurons were analyzed mathematically by Q-technique principal components analysis and cluster analysis to identify basic neuronal patterns of response. Four distinct patterns emerged which, based on the average profiles of response, were characterized as: NaCl-dominant, NaCl-HCl, sucrose-dominant, and non-specific. Analysis of the NaCl- and sucrose-dominant types of neurons indicated that neurons with the most narrowly tuned patterns of response to the taste stimuli could not effectively code specific taste qualities. Comparison of interstimulus correlations in magnitude of response across neurons between qualitatively different tastants and intrastimulus correlations between intensities of given tastants also revealed difficulties with the spatial pattern model of coding. The discrepant findings raise questions about an assumption utilized in the analysis of the model, viz., that all elements contribute homogeneously to the patterning code.

Animals↗

Gustatory processing in thoracic local circuits of locusts.

Recent reviews highlight a longstanding controversy about how different taste qualities are coded in the CNS. To address this issue, we have analyzed gustatory coding in the relatively simple and accessible nervous system of the locust, in which neural responses and gustatory elicited behavior are readily comparable. The intracellular responses of a population of spiking local interneurons in the metathoracic ganglion that receive monosynaptic inputs from chemosensory afferents were analyzed in response to stimulation with droplets of four behaviorally relevant chemicals: sodium chloride, sucrose, lysine glutamate, and nicotine hydrogen tartrate. There was a significant positive correlation between chemical concentration and response duration and the number of spikes evoked in 81% of interneurons sampled. The threshold of sensitivity to different chemicals varied but was consistent between all interneurons tested, being most sensitive to nicotine hydrogen tartrate and least sensitive to sucrose. Each interneuron responded similarly to specific chemicals at single concentrations. Interneurons that responded phasically to one chemical responded similarly to others, whereas interneurons that responded phasotonically to one stimulus also did so to others. Hindleg motor neurons also responded in a concentration-dependent manner to all test chemicals. Therefore, we found no interneurons or motor neurons that responded only to specific chemicals. We discuss the responses of the local circuit neurons in relation to the known chemically evoked behavioral responses of locusts and suggest that the aversiveness of a chemical, rather than its identity, is encoded directly in the local circuits.

Action Potentials↗

Temporal coding in the gustatory system.

Early investigations of temporal coding in the gustatory system showed that the time course of responses in some neurons showed systematic differences across the various classes of taste stimuli, implying that the temporal characteristics of a response can convey information about a taste stimulus. Studies of temporal coding in the gustatory system have grappled with several unique methodological challenges, including the quantitative description and comparison of temporal patterns as well as the assessment of the relative contributions of spatial and temporal coding to the information contained in a response to a tastant. Other investigations have suggested that the cooperative activity among synchronously firing ensembles of taste-responsive neurons at all levels of processing in the brain can convey information about taste quality (sweet, sour, salty, bitter and umami). Behavioral studies using patterned electrical stimulation of the brain in awake animals have supported the idea that temporal coding of taste stimuli may have functional significance.

Animals↗

[Physiology of smell and taste].

The functional organization of olfaction and taste are briefly discussed in morphological, physiological, biochemical and behavioural terms. Olfaction in animals serves often for long range navigational purposes whereas taste acts as a close up "last moment food checking system". Special attention is given to the coding problems in both systems. In taste, the spatial coding mode is prevalent. In olfaction a very complex coding system exists, which used temporal as well as spatial means and in which a whole set of olfactory nerve fibers is activated during the transmission of any specific odor information, each fiber of the set discharging at a specific impulse pattern. The role of the olfactory bulb is seen as an integrating center with the capabilities for short and long term information storage. The impact of von Békésy's microstimulation experiments on the physiology of taste is discussed. Research on taste modifiers such as gymnemic acid or of the taste modifying protein "miraculin" enrich our present understanding of the interaction between taste stimulants and the chemoreceptor sites in the taste buds.

Animals↗

Sensitivity of rat cortical neurons in distinguishing taste qualities by individual and correlative activities.

To examine the possibility that different taste qualities are represented by the correlative activity of cortical gustatory neurons, we made simultaneous recordings of neuron pairs during application of four basic tastes into the oral cavity of anesthetized rats and the following observations were made: (i) in 30 of 67 pairs of taste responsive neurons, peaks (troughs in a few cases) were produced in the cross-correlograms (CCs) during stimulation with some tastants; (ii) the correlative discharges occupied 6-8% of the total spikes discharged by individual neurons during taste stimulation and occurred, in a considerable number of cases, even during stimulation with tastants to which one or both of the component neurons of a pair were apparently non-responding (often sucrose and quinine); (iii) the number of tastants to which a neuron pair responded with a significant correlative activity was often greater than the number of tastants to which the component neurons of the same pair responded with significant changes in discharge rate; (iv) there was no significant difference between the correlative (formation of peaks or troughs in the CC) and individual (change in discharge rate of individual neurons) ways of coding in the sensitivity to distinguish between two taste qualities ranked to be adjacent on the basis of the number of spikes composing the response; and (v) the peaks or troughs appearing in two CCs during stimulations with two kinds of tastants were compared with regard to overlapping of their delay ranges and widths. The spikes in the non-overlapping portion of each peak (suppressed spike number in the case of troughs) are supposed to be able to contribute to two-taste discrimination: the correlated discharges occurring with a delay time that corresponds to the overlapping portion can in no way be judged differently, but the spikes falling in the non-overlapping portion may contribute to the differentiation. The ratio of the non-overlapping portion to the entire peak (or trough) was 0.35 on average. It is concluded that temporal coding of taste qualities seems to operate effectively in the gustatory cortex.

Animals↗

Expression of catfish amino acid taste receptors in Xenopus oocytes.

We demonstrate that poly (A+)RNA isolated from catfish barbels directs the expression of functional amino acid taste receptors in the Xenopus oocyte. The activity of these receptors is monitored in ovo by the two electrode voltage clamp technique. Specific conductance changes recorded in response to amino acid stimulation are analogous to those recorded electrophysiologically from intact catfish barbels. These responses exhibit specificity, reproducibility, rapid onset and termination, and desensitization to repetitive stimulation. A functional assay system that encompasses the full complement of transduction events from the ligand-receptor interaction to subsequent conductance changes is necessary to identify molecular components responsible for these events. Our results demonstrate that the Xenopus oocyte can be used to characterize and identify clones coding for amino acid taste receptors analogous to its use in studying receptor molecules for other neuroactive compounds.

Amino Acids↗

Human taste genetics.

Humans show substantial differences in taste sensitivity to many different substances. Some of this variation is known to be genetic in origin, and many other inter-individual differences are likely to be partially or wholly determined by genetic mechanisms. Recent advances in the understanding of taste at the molecular level have provided candidate genes that can be evaluated for contributions to phenotypic differences in taste abilities. This approach has provided an understanding of variation in the ability to taste phenylthiocarbamide (PTC), and has resolved long-standing controversies about the genetics of this classic human genetic trait. Significant coding sequence variation exists in taste receptor genes, which suggests that PTC tasting may indicate more general taste sensory variation. However, many aspects of taste perception remain poorly characterized. Better understanding of the molecular components of salty and sour tastes is still needed, as is a more complete picture of second messenger and downstream signaling mechanisms for all taste modalities. More general studies of linkage and association between genetic markers and taste phenotypes may reveal genes encoding proteins that were previously unsuspected to be involved in this sensory process.

Evolution, Molecular↗

Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence.

A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta -glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta -glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans (minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population.

Black or African American↗

Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide.

The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product.

Alleles↗

The neural mechanisms of gustation: a distributed processing code.

Whenever food is placed in the mouth, taste receptors are stimulated. Simultaneously, different types of sensory fibre that monitor several food attributes such as texture, temperature and odour are activated. Here, we evaluate taste and oral somatosensory peripheral transduction mechanisms as well as the multi-sensory integrative functions of the central pathways that support the complex sensations that we usually associate with gustation. On the basis of recent experimental data, we argue that these brain circuits make use of distributed ensemble codes that represent the sensory and post-ingestive properties of tastants.

Afferent Pathways↗

Across unit patterns in the neural response to taste: vector space analysis.

1. In the study of the neural code for gustation, it has been suggested that the pattern of responsiveness across fibers or units in the neural pathway for taste may provide the basis for identification and discrimination among taste qualities. Two possible mechanisms of comparison between pairs of stimuli were discussed, as follows: 1) a labeled-line code, where one subset of units responds to one stimulus but not the other, and a second subset of units responds in just the opposite fashion; and 2) a frequency code, where all units always respond well to one stimulus and always respond poorly to the other. 2. Conventional analyses of across unit patterns of response in the taste system have employed the Pearson product-moment correlation and/or the neural mass difference as measures of similarity. These measures consider the relative firing rates for a given pair of stimuli (correlation) or the averaged absolute differences in the firing rates (neural mass difference) evoked by two stimuli. Neither of these metrics considers both the absolute and the relative strengths of response to a given pair of stimuli in the comparison of across unit patterns. 3. A new approach to the analysis of across unit patterns of response, called vector space analysis, was described. With this method, the responses to a given stimulus across units are viewed as a vector in n-dimensional space, where n is the number of units in the sample. The length of each vector provides an index of the overall strength of the response to a particular tastant, and the angle between two vectors is a measure of the similarity of the across unit patterns for a given pair of tastants. 4. A neural discrimination (delta, delta) was derived from this approach as a measure of the similarity of two vectors that incorporates information about both the overall magnitude of response and the distribution of responses across units for a given pair of of stimuli. A labeled line index (lambda, lambda) was also proposed to indicate the extent to which the discrimination between two stimuli may be encoded by the responses in two separate subsets of units. 5. Electrophysiological responses to representatives of the four basic taste qualities (salty, sour, sweet, and bitter) were recorded in 47 single units located in the parabrachial nucleus of the pons (PbN) of the rat. Conventional and vector space analyses were applied to the across unit patterns that were recorded from these units. Multidimensional scaling techniques were used to compare the results of each analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neurons in the cortical taste area receive nociceptive inputs from the whole body as well as the oral cavity in the rat.

Almost all mechanoreceptive neurons in the cortical taste area (CTA) of the rat had receptive fields (RFs) in the oral cavity, except for a few neurons at the border with the primary somatosensory area that had RFs on the contralateral rhinarium or upper lip. About one-third of the mechanoreceptive neurons with RFs in the oral cavity had additional RFs on the tips of limbs, earflaps or tail, i.e. the glabrous skin or skin with sparse hairs of the external surface of the body (whole body type). Most of these neurons received both innocuous and noxious inputs (wide dynamic range type), but some had either type of input (low threshold mechanoreceptive or nociceptive specific type). Some nociceptive neurons were responsive to taste, as previously found. Nociceptive neurons with the whole body type of RFs were diffusely distributed across the CTA without clustering. The corticocortical afferents, probably originating from the visceral part of the insula, may code body condition to modulate the taste responsiveness of the cortical taste neurons.

Animals↗

Gustatory neural coding in the pons.

Third-order neurons from the pontine taste area (PTA) were analyzed in accordance with the across-fiber pattern theory of gustatory neural coding. Single neuron responses, evoked by chemical stimulation of the tongue, were recorded from the PTA of acute Nembutalized rats. They reveal that PTA neurons are broadly sensitive to stimuli representing the 4 putative basic taste qualities. Of 35 neurons, 33 responded to at least 3 of the 4 quality classes. Time course analyses indicate that stimuli which are shown to be alike in behavioral studies exhibit similar temporal response sequences. Correlations between all possible pairs of response patterns indicate that like-tasting chemicals elicit similar profiles of activity across the neural population. A multidimensional analysis indicates that three underlying physico-chemical dimensions (as yet undefined) bear upon the neural responses. In certain of their response properties, PTA neurons are like those of the (second-order) solitary nucleus; in other respects they auger the characteristics seen in the (fourth-order) thalamic neurons. It is concluded that the PTA is functionally as well as anatomically intermediate between the solitary nucleus and thalamus in the taste processing chain.

Animals↗

Time-quality tracking of monosodium glutamate, sodium saccharin, and a citric acid-saccharin mixture.

The temporal patterns of taste-quality descriptors evoked by 1000-ms duration stimulus liquids flowed through a closed delivery system over the anterodorsal tongue tip region were indicated using touch-typing on a computer keyboard. Single keys corresponded to the taste words of a 23 item code. A computer monitor displayed for subjects the keys pressed and when they were pressed, starting at stimulus delivery. For 2 mM sodium saccharin (NaSac), 75% of the responses were "sweet," 6.5% "sugar"; for NaSac in 10 mM citric acid (ArtLem), 43% "sour," 20% "citrus," and 11% "sugar"; for 214 mM monosodium glutamate (MSG), 28% "salty," 14% "sour," and 10% 1st "soapy," then "no taste," and finally "bitter." Distilled water received "no taste" on all trials. Response durations were 657 ms for ArtLem, 594 ms for NaSac, 577 ms for MSG. MSG yielded multiple quality responses on 25.5% of the trials; ArtLem, 9%; and NaSac, 1%. These results are compared with temporal patterns for taste intensity and with unrestricted verbal descriptions of the solutions.

Adolescent↗