Taste Pathways Research Articles

Connectomic analysis of taste circuits in Drosophila.

Our sense of taste is critical for regulating food consumption. The fruit fly Drosophila represents a highly tractable model to investigate mechanisms of taste processing, but taste circuits beyond sensory neurons are largely unidentified. Here, we use a whole-brain connectome to investigate the organization of Drosophila taste circuits. We trace pathways from four populations of sensory neurons that detect different taste modalities and project to the subesophageal zone (SEZ). We find that second-order taste neurons are primarily located within the SEZ and largely segregated by taste modality, whereas third-order neurons have more projections outside the SEZ and more overlap between modalities. Taste projections out of the SEZ innervate regions implicated in feeding, olfactory processing, and learning. We characterize interconnections between taste pathways, identify modality-dependent differences in taste neuron properties, and use computational simulations to relate connectivity to predicted activity. These studies provide insight into the architecture of Drosophila taste circuits.

Neural Processing of Taste-Related Signals in the Mediodorsal Thalamus of Mice.

Our consummatory decisions depend on the taste of food and the reward experienced while eating, which are processed through neural computations in interconnected brain areas. Although many gustatory regions of rodents have been explored, the mediodorsal nucleus of the thalamus (MD) remains understudied. The MD, a multimodal brain area connected with gustatory centers, is often studied for its role in processing associative and cognitive information and has been shown to represent intraorally-delivered chemosensory stimuli after strong retronasal odor-taste associations. Key questions remain about whether MD neurons can process taste quality independently of odor-taste associations and how they represent extraoral signals predicting rewarding and aversive gustatory outcomes. Here, we present electrophysiological evidence demonstrating how mouse MD neurons represent and encode 1) the identity and concentrations of basic taste qualities during active licking, and 2) auditory signals anticipating rewarding and aversive taste outcomes. Our data reveal that MD neurons can reliably and dynamically encode taste identity in a broadly tuned manner and taste concentrations with spiking activity positively and negatively correlated with stimulus intensity. Our data also show that MD can represent information related to predictive cues and their associated outcomes, regardless of whether the cue predicts a rewarding or aversive outcome. In summary, our findings suggest that the mediodorsal thalamus is integral to the taste pathway, as it can encode sensory-discriminative dimensions of tastants and participate in processing associative information essential for ingestive behaviors.

Taste and its receptors in human physiology: A comprehensive look

AbstractIncreasing evidence shows that food has significance beyond traditional perception (providing nutrition and energy) in maintaining normal life activities. It is indicated that the sense of taste plays a crucial part in regulating human life activities. Taste is one of the basic physiological sensations in mammals, and it is the fundamental guarantee for them to perceive, select, and ingest nutrients in order to survive. With the advances in electrophysiology, molecular biology, and structural biology, studies on the intracellular and extracellular transduction mechanisms of taste have made great progress and gradually revealed the indispensable role of taste receptors in the regulation and maintenance of normal physiological activities. Up to now, how food regulates life activities through the taste pathway remains unclear. Thus, this review comprehensively and systematically summarizes the current study about the sense of taste, the function of taste receptors, the taste–structure relationship of gustatory molecules, the cross‐talking between distinctive tastes, and the role of the gut–organ axis in the realization of taste. Moreover, we also provide forward‐looking perspectives on taste research to afford a scientific basis for revealing the scientific connotation of taste receptors regulating body health.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

Bedside Examination Technique for Taste.

Taste disorders are uncommon and frequently unrecognised during neurological and even oral examinations. Nevertheless, understanding taste pathway, its disorders, as well as assessment of taste are crucial as it can reveal various oral, systemic and neurological pathologies that manifest as an alteration of taste. Multiple taste examination techniques have been described in the literature; however, certain techniques are complicated and may not be feasible. This paper describes the adoption of a relatively simple technique for taste assessment that can be performed at the bedside. The bedside detection of taste disorders will allow examiners to assign the patient for more detailed and invasive taste assessments.

Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway.

On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the KATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake.

Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors.

Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl- is thought to participate in taste sensation through an unknown mechanism. Here, we describe Cl- ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl- binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl- binding induced a conformational change in T1r2a/T1r3LBD at sub- to low-mM concentrations, similar to canonical taste substances. Furthermore, oral Cl- application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl- evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration.

Regional specialization of the tongue revealed by gustatory ganglion imaging.

Gustatory information is relayed from the anterior tongue by geniculate ganglion neurons and from the posterior tongue by neurons of the petrosal portion of the jugular/nodose/petrosal ganglion complex. Here, we use invivo calcium imaging in mice to compare the encoding of taste information in the geniculate and petrosal ganglia, at single-neuron resolution. Our data support an anterior/posterior specialization of taste information coding from the tongue to the ganglia, with petrosal neurons more responsive to umami or bitter and less responsive to sweet or salty stimuli than geniculate neurons. We found that umami (50mM MPG+ 1mM IMP) promotes salivation when applied to the posterior, but not anterior, tongue. This suggests a functional taste map of the mammalian tongue where the anterior and posterior taste pathways are differentially responsive to specific taste qualities, and differentially regulate downstream physiological functions of taste, such as promoting salivation.

A data processing method for electronic tongue based on computational model of taste pathways and convolutional neural network

Research on the bionic degree of the electronic tongue (e-tongue) is limited. Therefore, a computational model of taste pathways and convolutional neural network (CMTP-CNN) is proposed for performance improvement while enhancing the bionic degree of the e-tongue. In this study, the enhancement effects of CMTP-CNN on the bionic degree are shown by simulation results. The simulation results demonstrate that the bionic degree of the e-tongue is enhanced by the fast-response ability and chaotic characteristics of CMTP nodes. Next, CMTP-CNN is used to identify tea and beer samples. Compared with the identification results of multiclass classification methods, the best accuracy of 96.00% and 96.67%, the best Kappa coefficients of 0.9495 and 0.9577, and the best area under the curve values of 0.9750 and 0.9792 in the tea and beer recognition, respectively, are acquired by CMTP-CNN. In conclusion, an improved identification performance for taste substances with the e-tongue is achieved using CMTP-CNN.

Molecular and Cellular Mechanisms of Salt Taste.

Salt taste, the taste of sodium chloride (NaCl), is mechanistically one of the most complex and puzzling among basic tastes. Sodium has essential functions in the body but causes harm in excess. Thus, animals use salt taste to ingest the right amount of salt, which fluctuates by physiological needs: typically, attraction to low salt concentrations and rejection of high salt. This concentration-valence relationship is universally observed in terrestrial animals, and research has revealed complex peripheral codes for NaCl involving multiple taste pathways of opposing valence. Sodium-dependent and -independent pathways mediate attraction and aversion to NaCl, respectively. Gustatory sensors and cells that transduce NaCl have been uncovered, along with downstream signal transduction and neurotransmission mechanisms. However, much remains unknown. This article reviews classical and recent advances in our understanding of the molecular and cellular mechanisms underlying salt taste in mammals and insects and discusses perspectives on human salt taste.

Taste sensation evaluation for an electronic tongue based on an optimized computational model of taste pathways

Effective evaluation of taste sensation can be achieved by analyzing electronic tongue (e-tongue) data. Research on evaluation of the taste sensation of an e-tongue by nerve conduction mechanisms is limited, which obviously affects performance evaluation of e-tongues. Therefore, in this paper, a method for evaluating the taste sensation of an e-tongue based on human taste conduction mechanisms, the computational model of taste pathways (CMTP), is proposed. However, the limited physiological basis of the CMTP parameters influences the evaluation results. To achieve excellent evaluation performance, a parameter optimization algorithm with Hebbian and habituation learning rules is used to optimize the CMTP parameters. The effectiveness of the optimized results is demonstrated by improvement in the dynamic characteristics of the CMTP. Next, the optimized CMTP (OCMTP) is used for pattern recognition and sweetness evaluation of four taste substances. The results showed, first, that the dynamic characteristics (including 1/f characteristics and synchronization) of the OCMTP are improved, and the bionics of the OCMTP is enhanced. The optimized results are effective. Second, compared with the recognition results for the four taste substances by the unoptimized CMTP (UCMTP), signal preprocessing methods and multiclass classification models, the best classification accuracy (95.38%), the best kappa coefficient (93.83%) and the best F 1-score (96.10%) are achieved by the OCMTP. Finally, compared with the sweetness evaluation results of the UCMTP, signal preprocessing methods and multiple evaluation models, the best evaluation performance, including a root-mean-square error of 0.1643 and R 2 of 0.9785, is obtained using the OCMTP. In conclusion, effective evaluation of taste sensation can be achieved by the OCMTP and an e-tongue.

Taste quality and hunger interactions in a feeding sensorimotor circuit.

Taste detection and hunger state dynamically regulate the decision to initiate feeding. To study how context-appropriate feeding decisions are generated, we combined synaptic resolution circuit reconstruction with targeted genetic access to specific neurons to elucidate a gustatory sensorimotor circuit for feeding initiation in adult Drosophila melanogaster. This circuit connects gustatory sensory neurons to proboscis motor neurons through three intermediate layers. Most neurons in this pathway are necessary and sufficient for proboscis extension, a feeding initiation behavior, and respond selectively to sugar taste detection. Pathway activity is amplified by hunger signals that act at select second-order neurons to promote feeding initiation in food-deprived animals. In contrast, the feeding initiation circuit is inhibited by a bitter taste pathway that impinges on premotor neurons, illuminating a local motif that weighs sugar and bitter taste detection to adjust the behavioral outcomes. Together, these studies reveal central mechanisms for the integration of external taste detection and internal nutritive state to flexibly execute a critical feeding decision.

A molecular mechanism for high salt taste in Drosophila

Dietary salt detection and consumption are crucial to maintaining fluid and ionic homeostasis. To optimize salt intake, animals employ salt-dependent activation of multiple taste pathways. Generally, sodium activates attractive taste cells, but attraction is overridden at high salt concentrations by cation non-selective activation of aversive taste cells. In flies, high salt avoidance is driven by both "bitter" taste neurons and a class of glutamatergic "high salt" neurons expressing pickpocket23 (ppk23). Although the cellular basis of salt taste has been described, many of the molecular mechanisms remain elusive. Here, we show that ionotropic receptor 7c (IR7c) is expressed in glutamatergic high salt neurons, where it functions with co-receptors IR76b and IR25a to detect high salt and is essential for monovalent salt taste. Misexpression of IR7c in sweet neurons, which endogenously express IR76b and IR25a, confers responsiveness to non-sodium salts, indicating that IR7c is sufficient to convert a sodium-selective gustatory receptor neuron to a cation non-selective one. Furthermore, the resultant transformation of taste neuron tuning switches potassium chloride from an aversive to an attractive tastant. This research provides insight into the molecular basis of monovalent and divalent salt-taste coding.

Computational Model of Taste Pathways: A Biomimetic Algorithm for Electronic Tongue Based on Nerve Conduction Mechanism

Research on the taste conduction mechanisms of data processing by the electronic tongue (e-tongue) is lacking. These mechanisms affect taste substance identification by the e-tongue system. This work proposed a computational model of taste pathways based on nerve conduction mechanisms to identify taste substances. This work modelled human taste pathways based on the Katchalsky models and validated the rationality of the modelling forms of the critical pathway structures. Next, this work simulated the response status and power spectral density of the model nodes and verified the bionic performance of the computational model. The results showed, first, that the computational model described the dynamic characteristics of the taste pathways. Second, the phase diagrams of the pathway structures revealed chaotic characteristics. This result showed that the modelling forms were rational. Third, when stimulated, the model nodes exhibited fast responses. During stimulation, the power spectral density of the model nodes demonstrated 1/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}$ </tex-math></inline-formula> characteristics. The fast-response ability and 1/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}$ </tex-math></inline-formula> characteristics reflected the bionic performance of the computational model. Finally, the computational model was used to identify beer, tea, and apple samples. Compared with other classification methods, the computational model achieved better classification results of 93.33%, 94.00%, and 76.67%, the best specificity of 0.9833, 0.9850, and 0.9417, and the best Kappa coefficients of 0.9180, 0.9261, and 0.7245 for the identification of the beer, tea, and apple samples, respectively. In conclusion, the computational model can effectively identify taste substances.

Ultrastructure of Rat Rostral Nucleus of the Solitary Tract Terminals in the Parabrachial Nucleus and Medullary Reticular Formation.

Neurons in the rostral nucleus of the solitary tract (rNST) receive taste information from the tongue and relay it mainly to the parabrachial nucleus (PBN) and the medullary reticular formation (RF) through two functionally different neural circuits. To help understand how the information from the rNST neurons is transmitted within these brainstem relay nuclei in the taste pathway, we examined the terminals of the rNST neurons in the PBN and RF by use of anterograde horseradish peroxidase (HRP) labeling, postembedding immunogold staining for glutamate, serial section electron microscopy, and quantitative analysis. Most of the anterogradely labeled, glutamate-immunopositive axon terminals made a synaptic contact with only a single postsynaptic element in PBN and RF, suggesting that the sensory information from rNST neurons, at the individual terminal level, is not passed to multiple target cells. Labeled terminals were usually presynaptic to distal dendritic shafts in both target nuclei. However, the frequency of labeled terminals that contacted dendritic spines was significantly higher in the PBN than in the RF, and the frequency of labeled terminals that contacted somata or proximal dendrites was significantly higher in the RF than in the PBN. Labeled terminals receiving axoaxonic synapses, which are a morphological substrate for presynaptic modulation frequently found in primary sensory afferents, were not observed. These findings suggest that the sensory information from rNST neurons is processed in a relatively simple manner in both PBN and RF, but in a distinctly different manner in the PBN as opposed to the RF.

Evidence that human oral glucose detection involves a sweet taste pathway and a glucose transporter pathway.

The taste stimulus glucose comprises approximately half of the commercial sugar sweeteners used today, whether in the form of the di-saccharide sucrose (glucose-fructose) or half of high-fructose corn syrup (HFCS). Therefore, oral glucose has been presumed to contribute to the sweet taste of foods when combined with fructose. In light of recent rodent data on the role of oral metabolic glucose signaling, we examined psychopharmacologically whether oral glucose detection may also involve an additional pathway in humans to the traditional sweet taste transduction via the class 1 taste receptors T1R2/T1R3. In a series of experiments, we first compared oral glucose detection thresholds to sucralose thresholds without and with addition of the T1R receptor inhibitor Na-lactisole. Next, we compared oral detection thresholds of glucose to sucralose and to the non-metabolizable glucose analog, α-methyl-D-glucopyranoside (MDG) without and with the addition of the glucose co-transport component sodium (NaCl). Finally, we compared oral detection thresholds for glucose, MDG, fructose, and sucralose without and with the sodium-glucose co-transporter (SGLT) inhibitor phlorizin. In each experiment, psychopharmacological data were consistent with glucose engaging an additional signaling pathway to the sweet taste receptor T1R2/T1R3 pathway. Na-lactisole addition impaired detection of the non-caloric sweetener sucralose much more than it did glucose, consistent with glucose using an additional signaling pathway. The addition of NaCl had a beneficial impact on the detection of glucose and its analog MDG and impaired sucralose detection, consistent with glucose utilizing a sodium-glucose co-transporter. The addition of the SGLT inhibitor phlorizin impaired detection of glucose and MDG more than it did sucralose, and had no effect on fructose, further evidence consistent with glucose utilizing a sodium-glucose co-transporter. Together, these results support the idea that oral detection of glucose engages two signaling pathways: one that is comprised of the T1R2/T1R3 sweet taste receptor and the other that utilizes an SGLT glucose transporter.

Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation.

Sweetness is the preferred taste of humans and many animals, likely because sugars are a primary source of energy. In many mammals, sweet compounds are sensed in the tongue by the gustatory organ, the taste buds. Here, a group of taste bud cells expresses a canonical sweet taste receptor, whose activation induces Ca2+ rise, cell depolarization and ATP release to communicate with afferent gustatory nerves. The discovery of the sweet taste receptor, 20 years ago, was a milestone in the understanding of sweet signal transduction and is described here from a historical perspective. Our review briefly summarizes the major findings of the canonical sweet taste pathway, and then focuses on molecular details, about the related downstream signaling, that are still elusive or have been neglected. In this context, we discuss evidence supporting the existence of an alternative pathway, independent of the sweet taste receptor, to sense sugars and its proposed role in glucose homeostasis. Further, given that sweet taste receptor expression has been reported in many other organs, the physiological role of these extraoral receptors is addressed. Finally, and along these lines, we expand on the multiple direct and indirect effects of sugars on the brain. In summary, the review tries to stimulate a comprehensive understanding of how sweet compounds signal to the brain upon taste bud cells activation, and how this gustatory process is integrated with gastro-intestinal sugar sensing to create a hedonic and metabolic representation of sugars, which finally drives our behavior. Understanding of this is indeed a crucial step in developing new strategies to prevent obesity and associated diseases.

Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity.

Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity.

Taste changes in orofacial pain conditions and coronavirus disease 2019: a review

Background and Objectives: Taste sensation has a significant evolutionary, nutritional and protective role in human beings. Changes in the perception of taste can significantly affect the overall quality of life of an individual. A significant proportion of patients with taste changes such as ageusia (complete loss of taste), hypogeusia (diminished taste sensation), dysgeusia (altered/distorted taste sensation including taste phantoms like metallic/bitter taste) present to the dental and medical healthcare professionals. The objective of the narrative review is to familiarize healthcare professionals with taste changes in orofacial pain conditions and coronavirus disease 2019. The manuscript objective of the narrative review is to familiarize the dental and medical healthcare professionals with the taste pathway and pathophysiological mechanisms, diagnostic testing and management.

Two neuronal groups for NaCl with differential taste response properties and topographical distributions in the rat parabrachial nucleus.

It is crucial for animals to discriminate between palatable (safe) and aversive (toxic) tastants. The mechanisms underlying neuronal discrimination of taste stimuli remain unclear. We examined relations between taste response properties (spike counts, response duration, and coefficient of variation [CV]) and location of taste‐sensitive neurons in the pontine parabrachial nucleus (PBN). Extracellular single units’ activity in the PBN of Wistar rats was recorded using multibarrel glass micropipettes under urethane anesthesia. Forty taste‐sensitive neurons were classified as NaCl (N)‐best (n = 15), NaCl/HCl (NH)‐best (n = 14), HCl (H)‐best (n = 8), and sucrose (S)‐best (n = 3) neurons. The net response to NaCl (15.2 ± 2.3 spikes/s) among the N‐best neurons was significantly larger than that among the NH‐best (4.5 ± 0.8 spikes/s) neurons. The response duration (4.5 ± 0.2 s) of the N‐best neurons to NaCl was significantly longer than that of the NH‐best (2.2 ± 0.3 s) neurons. These differences in the spike counts and the response durations between the two neuronal types in the PBN were similar to that previously reported in the rostral nucleus of the solitary tract (rNST). The CVs in the N‐best and the NH‐best neurons were significantly smaller in the PBN than those in the rNST. Histologically, most N‐best neurons (12/13, 92%) were localized to the medial region, while NH‐best neurons (11/13, 85%) were primarily found within the brachium conjunctivum. These results suggest that NaCl‐specific taste information is transmitted by two distinct neuronal groups (N‐best and NH‐best), with different taste properties and locations within rNST to PBN tractography. Future studies on the higher order nuclei for taste could reveal more palatable and aversive taste pathways.