The coding of valence and identity in the mammalian taste system.
ABSTRACT: The ability of the taste system to identify a tastant (what it tastes like) enables animals to recognize and discriminate between the different basic taste qualities1,2. The valence of a tastant (whether it is appetitive or aversive) specifies its hedonic value and elicits the execution of selective behaviours. Here we examine how sweet and bitter are afforded valence versus identity in mice. We show that neurons in the sweet-responsive and bitter-responsive cortex project to topographically distinct areas of the amygdala, with strong segregation of neural projections conveying appetitive versus aversive taste signals. By manipulating selective taste inputs to the amygdala, we show that it is possible to impose positive or negative valence on a neutral water stimulus, and even to reverse the hedonic value of a sweet or bitter tastant. Remarkably, mice with silenced neurons in the amygdala no longer exhibit behaviour that reflects the valence associated with direct stimulation of the taste cortex, or with delivery of sweet and bitter chemicals. Nonetheless, these mice can still identify and discriminate between tastants, just as wild-type controls do. These results help to explain how the taste system generates stereotypic and predetermined attractive and aversive taste behaviours, and support the existence of distinct neural substrates for the discrimination of taste identity and the assignment of valence.
Project description:Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviours, preventing the ingestion of toxic substances, and helping to ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste allows the identification of energy-rich nutrients whereas bitter warns against the intake of potentially noxious chemicals. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map, with each taste quality encoded by distinct cortical fields. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal's internal representation, sensory perception, and behavioural actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviours in the absence of sensory input.
Project description:Taste circuits are genetically determined to elicit an innate appetitive or aversive response, ensuring that animals consume nutritious foods and avoid the ingestion of toxins. We have examined the response of <i>Drosophila melanogaster</i> to acetic acid, a tastant that can be a metabolic resource but can also be toxic to the fly. Our data reveal that flies accommodate these conflicting attributes of acetic acid by virtue of a hunger-dependent switch in their behavioral response to this stimulus. Fed flies show taste aversion to acetic acid, whereas starved flies show a robust appetitive response. These opposing responses are mediated by two different classes of taste neurons, the sugar- and bitter-sensing neurons. Hunger shifts the behavioral response from aversion to attraction by enhancing the appetitive sugar pathway as well as suppressing the aversive bitter pathway. Thus a single tastant can drive opposing behaviors by activating distinct taste pathways modulated by internal state.
Project description:In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami. Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one. This appetitive-aversive balance helps to maintain appropriate salt consumption, and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the 'co-opting' of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.
Project description:Outbred rats display variable preferences for bittersweet solutions, expressed as preference or avoidance of high concentrations of artificial sweeteners over water. This may reflect individual differences in appetitive/aversive conflict processing that may have predictive validity for disorders of motivation. Here we use a homecage two-bottle choice procedure to examine the test/retest stability and between-tastant consistency in sucralose preference to determine the reliability of bittersweet taste preference. Sucralose is a non-caloric artificial sweetener that is preferred by some rats and avoided by others. We sought to determine whether sucralose preference is consistent with preference of sucrose/quinine solutions that have known sweet and bitter taste qualities, respectively. We give fluid restricted rats 45-minutes homecage access to water and ascending concentrations of sucralose (SUCRA; 0.0025-10mM) or a compound solution of sucrose (116mM) + quinine (0.002-2mM) (SQ). We use a within-subject counterbalanced design (SUCRA or SQ testing) to determine preference of each bittersweet solution relative to water. We observed individual variability in preference for SUCRA and SQ, such that some rats preferred bittersweet solutions over water (preferring) while other rats preferred water over bittersweet solutions (avoiding). Within tastant, this preference remained stable across repeated testing. Between solutions, SUCRA preference scores correlated with SQ scores, suggesting consistent taste conflict processing for both bittersweet solutions. Population level analyses confirmed that preference generalizes across bittersweet solutions, and that rats' preferences for bittersweet solutions relative to water are stable over time. The test/retest and between-tastant reliability of this taste conflict screening procedure support the potential utility of this model for exploring individual variability in appetitive/aversive conflict processes mediating motivated behavior.
Project description:The sense of taste is important for providing animals with valuable information about the qualities of food, such as nutritional or harmful nature. Mammals, including humans, can recognize at least five primary taste qualities: sweet, umami (savory), bitter, sour, and salty. Recent studies have identified molecules and mechanisms underlying the initial steps of tastant-triggered molecular events in taste bud cells, particularly the requirement of increased cytosolic free Ca(2+) concentration ([Ca(2+)](c)) for normal taste signal transduction and transmission. Little, however, is known about the mechanisms controlling the removal of elevated [Ca(2+)](c) from the cytosol of taste receptor cells (TRCs) and how the disruption of these mechanisms affects taste perception. To investigate the molecular mechanism of Ca(2+) clearance in TRCs, we sought the molecules involved in [Ca(2+)](c) regulation using a single-taste-cell transcriptome approach. We found that Serca3, a member of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) family that sequesters cytosolic Ca(2+) into endoplasmic reticulum, is exclusively expressed in sweet/umami/bitter TRCs, which rely on intracellular Ca(2+) release for signaling. Serca3-knockout (KO) mice displayed significantly increased aversive behavioral responses and greater gustatory nerve responses to bitter taste substances but not to sweet or umami taste substances. Further studies showed that Serca2 was mainly expressed in the T1R3-expressing sweet and umami TRCs, suggesting that the loss of function of Serca3 was possibly compensated by Serca2 in these TRCs in the mutant mice. Our data demonstrate that the SERCA family members play an important role in the Ca(2+) clearance in TRCs and that mutation of these proteins may alter bitter and perhaps sweet and umami taste perception.
Project description:Gustatory receptors and peripheral taste cells have been identified in flies and mammals, revealing that sensory cells are tuned to taste modality across species. How taste modalities are processed in higher brain centers to guide feeding decisions is unresolved. Here, we developed a large-scale calcium-imaging approach coupled with cell labeling to examine how different taste modalities are processed in the fly brain. These studies reveal that sweet, bitter, and water sensory cells activate different cell populations throughout the subesophageal zone, with most cells responding to a single taste modality. Pathways for sweet and bitter tastes are segregated from sensory input to motor output, and this segregation is maintained in higher brain areas, including regions implicated in learning and neuromodulation. Our work reveals independent processing of appetitive and aversive tastes, suggesting that flies and mammals use a similar coding strategy to ensure innate responses to salient compounds.
Project description:Bitter taste is aversive to humans, and many oral medications exhibit a bitter taste. Bitter taste can be suppressed by the use of inhibitors or by masking agents such as sucralose. Another approach is to encapsulate bitter tasting compounds in order to delay their release. This delayed release can permit the prior release of bitter masking agents. Suppression of bitter taste was accomplished by encapsulating a bitter taste stimulus in erodible stearic acid microspheres, and embedding these 5?µmeter diameter microspheres in pullulan films that contain sucralose and peppermint oil as masking agents, along with an encapsulated masking agent (sucralose). Psychophysical tests demonstrated that films which encapsulated both quinine and sucralose produced a significant and continuous sweet percept when compared to films without sucralose microspheres. Films with both quinine and sucralose microspheres also produced positive hedonic scores that did not differ from control films that contained only sucralose microspheres or only empty (blank) microspheres. The encapsulation of bitter taste stimuli in lipid microspheres, and embedding these microspheres in rapidly dissolving edible taste films that contain masking agents in both the film base and in microspheres, is a promising approach for diminishing the bitter taste of drugs and related compounds.
Project description:An organism's behavioral decisions often depend upon the relative strength of appetitive and aversive sensory stimuli, the relative sensitivity to which can be modified by internal states like hunger. However, whether sensitivity to such opposing influences is modulated in a unidirectional or bidirectional manner is not clear. Starved flies exhibit increased sugar and decreased bitter sensitivity. It is widely believed that only sugar sensitivity changes, and that this masks bitter sensitivity. Here we use gene- and circuit-level manipulations to show that sweet and bitter sensitivity are independently and reciprocally regulated by starvation in Drosophila. We identify orthogonal neuromodulatory cascades that oppositely control peripheral taste sensitivity for each modality. Moreover, these pathways are recruited at increasing hunger levels, such that low-risk changes (higher sugar sensitivity) precede high-risk changes (lower sensitivity to potentially toxic resources). In this way, state-intensity-dependent, reciprocal regulation of appetitive and aversive peripheral gustatory sensitivity permits flexible, adaptive feeding decisions.
Project description:In the mammalian brain, the insula is the primary cortical substrate involved in the perception of taste. Recent imaging studies in rodents have identified a "gustotopic" organization in the insula, whereby distinct insula regions are selectively responsive to one of the five basic tastes. However, numerous studies in monkeys have reported that gustatory cortical neurons are broadly-tuned to multiple tastes, and tastes are not represented in discrete spatial locations. Neuroimaging studies in humans have thus far been unable to discern between these two models, though this may be because of the relatively low spatial resolution used in taste studies to date. In the present study, we examined the spatial representation of taste within the human brain using ultra-high resolution functional magnetic resonance imaging (MRI) at high magnetic field strength (7-tesla). During scanning, male and female participants tasted sweet, salty, sour, and tasteless liquids, delivered via a custom-built MRI-compatible tastant-delivery system. Our univariate analyses revealed that all tastes (vs tasteless) activated primary taste cortex within the bilateral dorsal mid-insula, but no brain region exhibited a consistent preference for any individual taste. However, our multivariate searchlight analyses were able to reliably decode the identity of distinct tastes within those mid-insula regions, as well as brain regions involved in affect and reward, such as the striatum, orbitofrontal cortex, and amygdala. These results suggest that taste quality is not represented topographically, but by a distributed population code, both within primary taste cortex as well as regions involved in processing the hedonic and aversive properties of taste.SIGNIFICANCE STATEMENT The insula is the primary cortical substrate involved in taste perception, yet some question remains as to whether this region represents distinct tastes topographically or via a population code. Using high field (7-tesla), high-resolution functional magnetic resonance imaging in humans, we examined the representation of different tastes delivered during scanning. All tastes activated primary taste cortex within the bilateral mid-insula, but no brain region exhibited any consistent taste preference. However, multivariate analyses reliably decoded taste quality within the bilateral mid-insula as well as the striatum, orbitofrontal cortex, and bilateral amygdala. This suggests that taste quality is represented by a spatial population code within regions involved in sensory and appetitive properties of taste.
Project description:The gustatory system detects tastants and transmits signals to the brain regarding ingested substances and nutrients. Although tastant receptors and taste signaling pathways have been identified, little is known about their regulation. Because bitter, sweet, and umami taste receptors are G protein-coupled receptors (GPCRs), we hypothesized that regulators of G protein signaling (RGS) proteins may be involved. The recent cloning of RGS21 from taste bud cells has implicated this protein in the regulation of taste signaling; however, the exact role of RGS21 has not been precisely defined. Here, we sought to determine the role of RGS21 in tastant responsiveness. Biochemical analyses confirmed in silico predictions that RGS21 acts as a GTPase-accelerating protein (GAP) for multiple G protein ? subunits, including adenylyl cyclase-inhibitory (G?(i)) subunits and those thought to be involved in tastant signal transduction. Using a combination of in situ hybridization, RT-PCR, immunohistochemistry, and immunofluorescence, we demonstrate that RGS21 is not only endogenously expressed in mouse taste buds but also in lung airway epithelial cells, which have previously been shown to express components of the taste signaling cascade. Furthermore, as shown by reverse transcription-PCR, the immortalized human airway cell line 16HBE was found to express transcripts for tastant receptors, RGS21, and downstream taste signaling components. Over- and underexpression of RGS21 in 16HBE cells confirmed that RGS21 acts to oppose bitter tastant signaling to cAMP and calcium second messenger changes. Our data collectively suggests that RGS21 modulates bitter taste signal transduction.