RESUMEN
The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4-6. Here we show that a peripheral immune insult strongly activates the body-brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.
Asunto(s)
Encéfalo , Citocinas , Inflamación , Neuroinmunomodulación , Animales , Femenino , Masculino , Ratones , Encéfalo/citología , Encéfalo/inmunología , Encéfalo/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Ratones Endogámicos C57BL , Neuroinmunomodulación/inmunología , Neuroinmunomodulación/fisiología , Neuronas/fisiología , Nervio Vago/citología , Nervio Vago/fisiología , Análisis de Expresión Génica de una Sola CélulaRESUMEN
Real-time decisions on what foods to select for consumption, particularly in the wild, require a sensitive sense of taste and an effective system to maintain short-term taste memories, also defined as working memory in the scale of seconds. Here, we used a behavioral memory assay, combined with recordings of neural activity, to identify the brain substrate for short-term taste memories. We demonstrate that persistent activity in taste cortex functions as an essential memory trace of a recent taste experience. Next, we manipulated the decay of this persistent activity and showed that early termination of the memory trace abolished the memory. Notably, extending the memory trace by transiently disinhibiting taste cortical activity dramatically extended the retention of a short-term taste memory. Together, our results uncover taste cortex as a neural substrate for working memory and substantiate the role of sensory cortex in memory-guided actions while imposing meaning to a sensory stimulus.
Asunto(s)
Memoria a Corto Plazo , Gusto , Percepción del Gusto , Encéfalo , Lóbulo ParietalRESUMEN
Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet-related chronic disease.
RESUMEN
The perception of fat evokes strong appetitive and consummatory responses1. Here we show that fat stimuli can induce behavioural attraction even in the absence of a functional taste system2,3. We demonstrate that fat acts after ingestion via the gut-brain axis to drive preference for fat. Using single-cell data, we identified the vagal neurons responding to intestinal delivery of fat, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference. Next, we compared the gut-to-brain pathways driving preference for fat versus sugar4, and uncovered two parallel systems, one functioning as a general sensor of essential nutrients, responding to intestinal stimulation with sugar, fat and amino acids, whereas the other is activated only by fat stimuli. Finally, we engineered mice lacking candidate receptors to detect the presence of intestinal fat, and validated their role as the mediators of gut-to-brain fat-evoked responses. Together, these findings reveal distinct cells and receptors that use the gut-brain axis as a fundamental conduit for the development of fat preference.
Asunto(s)
Eje Cerebro-Intestino , Encéfalo , Preferencias Alimentarias , Intestinos , Neuronas , Animales , Ratones , Aminoácidos/metabolismo , Encéfalo/citología , Encéfalo/fisiología , Neuronas/metabolismo , Azúcares/metabolismo , Nervio Vago/citología , Nervio Vago/fisiología , Preferencias Alimentarias/fisiología , Análisis de la Célula Individual , Eje Cerebro-Intestino/genética , Eje Cerebro-Intestino/fisiología , Intestinos/inervación , Intestinos/metabolismoRESUMEN
Hardwired circuits encoding innate responses have emerged as an essential feature of the mammalian brain. Sweet and bitter evoke opposing predetermined behaviors. Sweet drives appetitive responses and consumption of energy-rich food sources, whereas bitter prevents ingestion of toxic chemicals. Here we identified and characterized the neurons in the brainstem that transmit sweet and bitter signals from the tongue to the cortex. Next we examined how the brain modulates this hardwired circuit to control taste behaviors. We dissect the basis for bitter-evoked suppression of sweet taste and show that the taste cortex and amygdala exert strong positive and negative feedback onto incoming bitter and sweet signals in the brainstem. Finally we demonstrate that blocking the feedback markedly alters responses to ethologically relevant taste stimuli. These results illustrate how hardwired circuits can be finely regulated by top-down control and reveal the neural basis of an indispensable behavioral response for all animals.
Asunto(s)
Amígdala del Cerebelo/fisiología , Encéfalo/fisiología , Mamíferos/fisiología , Gusto/fisiología , Animales , Tronco Encefálico/fisiología , Calbindina 2/metabolismo , Corteza Cerebral/fisiología , Retroalimentación Fisiológica , Ratones Endogámicos C57BL , Mutación/genética , Inhibición Neural/fisiología , Neuronas/fisiología , Núcleo Solitario/fisiología , Somatostatina/metabolismoRESUMEN
The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1-3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.
Asunto(s)
Encéfalo/fisiología , Conducta de Elección/fisiología , Azúcares de la Dieta/metabolismo , Preferencias Alimentarias/fisiología , Glucosa/metabolismo , Intestinos/fisiología , Animales , Encéfalo/citología , Azúcares de la Dieta/química , Glucosa/análogos & derivados , Glucosa/química , Masculino , Metilglucósidos/química , Metilglucósidos/metabolismo , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Gusto/fisiología , Tiazinas/metabolismo , Agua/metabolismoRESUMEN
The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled, or fermented foods. Taste and somatosensory receptors in the oral cavity trigger aversive behaviors in response to acid stimuli. Here, we show that the ion channel Otopetrin-1, a proton-selective channel normally involved in the sensation of gravity in the vestibular system, is essential for sour sensing in the taste system. We demonstrate that knockout of Otop1 eliminates acid responses from sour-sensing taste receptor cells (TRCs). In addition, we show that mice engineered to express otopetrin-1 in sweet TRCs have sweet cells that also respond to sour stimuli. Next, we genetically identified the taste ganglion neurons mediating each of the five basic taste qualities and demonstrate that sour taste uses its own dedicated labeled line from TRCs in the tongue to finely tuned taste neurons in the brain to trigger aversive behaviors.
Asunto(s)
Encéfalo/fisiología , Proteínas de la Membrana/metabolismo , Papilas Gustativas/metabolismo , Gusto , Ácidos/farmacología , Vías Aferentes/citología , Vías Aferentes/metabolismo , Vías Aferentes/fisiología , Animales , Encéfalo/citología , Encéfalo/metabolismo , Femenino , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Papilas Gustativas/efectos de los fármacos , Papilas Gustativas/fisiología , Percepción del GustoRESUMEN
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.
Asunto(s)
Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Conducta Apetitiva/fisiología , Reacción de Prevención/fisiología , Discriminación en Psicología/fisiología , Gusto/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Conducta Apetitiva/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Clozapina/análogos & derivados , Clozapina/farmacología , Discriminación en Psicología/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Neurológicos , Neuronas/efectos de los fármacos , Neuronas/fisiología , Gusto/efectos de los fármacos , Agua/farmacologíaRESUMEN
In mammals, taste buds typically contain 50-100 tightly packed taste-receptor cells (TRCs), representing all five basic qualities: sweet, sour, bitter, salty and umami. Notably, mature taste cells have life spans of only 5-20 days and, consequently, are constantly replenished by differentiation of taste stem cells. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (that is, ensuring that a labelled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, and so on), we examined how new connections are specified to retain fidelity of signal transmission. Here we show that bitter and sweet TRCs provide instructive signals to bitter and sweet target neurons via different guidance molecules (SEMA3A and SEMA7A). We demonstrate that targeted expression of SEMA3A or SEMA7A in different classes of TRCs produces peripheral taste systems with miswired sweet or bitter cells. Indeed, we engineered mice with bitter neurons that now responded to sweet tastants, sweet neurons that responded to bitter or sweet neurons responding to sour stimuli. Together, these results uncover the basic logic of the wiring of the taste system at the periphery, and illustrate how a labelled-line sensory circuit preserves signalling integrity despite rapid and stochastic turnover of receptor cells.
Asunto(s)
Células Madre/citología , Células Madre/metabolismo , Papilas Gustativas/citología , Papilas Gustativas/metabolismo , Gusto/fisiología , Animales , Antígenos CD/metabolismo , Ganglios/citología , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Semaforina-3A/deficiencia , Semaforina-3A/metabolismo , Semaforinas/metabolismo , Células Madre/efectos de los fármacos , Edulcorantes/farmacología , Gusto/efectos de los fármacos , Papilas Gustativas/efectos de los fármacosRESUMEN
Perception of the thermal environment begins with the activation of peripheral thermosensory neurons innervating the body surface. To understand how temperature is represented in vivo, we used genetically encoded calcium indicators to measure temperature-evoked responses in hundreds of neurons across the trigeminal ganglion. Our results show how warm, hot, and cold stimuli are represented by distinct population responses, uncover unique functional classes of thermosensory neurons mediating heat and cold sensing, and reveal the molecular logic for peripheral warmth sensing. Next, we examined how the peripheral somatosensory system is functionally reorganized to produce altered perception of the thermal environment after injury. We identify fundamental transformations in sensory coding, including the silencing and recruitment of large ensembles of neurons, providing a cellular basis for perceptual changes in temperature sensing, including heat hypersensitivity, persistence of heat perception, cold hyperalgesia, and cold analgesia.
Asunto(s)
Quemaduras/metabolismo , Hiperalgesia/metabolismo , Hiperestesia/metabolismo , Neuronas/metabolismo , Canales Catiónicos TRPV/metabolismo , Sensación Térmica/fisiología , Ganglio del Trigémino/citología , Animales , Quemaduras/fisiopatología , Frío , Calor , Hiperalgesia/fisiopatología , Hiperestesia/fisiopatología , Ratones , Ratones Noqueados , Ratones Transgénicos , Plasticidad Neuronal , Neuronas/fisiología , Canal Catiónico TRPA1 , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPV/genética , Canales de Potencial de Receptor Transitorio/genética , Canales de Potencial de Receptor Transitorio/metabolismo , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/fisiologíaRESUMEN
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.
Asunto(s)
Conducta Apetitiva/fisiología , Reacción de Prevención/fisiología , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Percepción del Gusto/fisiología , Gusto/fisiología , Vigilia/fisiología , Animales , Conducta Apetitiva/efectos de la radiación , Reacción de Prevención/efectos de la radiación , Mapeo Encefálico , Corteza Cerebral/efectos de la radiación , Discriminación en Psicología/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Optogenética , Técnicas Estereotáxicas , Percepción del Gusto/efectos de la radiaciónRESUMEN
Diet is a major issue facing humanity. To combat malnourishment and diseases associated with overnutrition, both research and technological breakthroughs are needed.
Asunto(s)
Encéfalo/fisiología , Alimentos , Salud Global , Proteínas en la Dieta/química , Alimentos/economía , Alimentos/historia , Tracto Gastrointestinal/microbiología , Historia Medieval , Humanos , Desnutrición/epidemiología , Microbiota , Vías Nerviosas , Hipernutrición/complicaciones , SacarosaRESUMEN
Thirst is the basic instinct to drink water. Previously, it was shown that neurons in several circumventricular organs of the hypothalamus are activated by thirst-inducing conditions. Here we identify two distinct, genetically separable neural populations in the subfornical organ that trigger or suppress thirst. We show that optogenetic activation of subfornical organ excitatory neurons, marked by the expression of the transcription factor ETV-1, evokes intense drinking behaviour, and does so even in fully water-satiated animals. The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus. In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals. These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.
Asunto(s)
Conducta de Ingestión de Líquido/fisiología , Órgano Subfornical/citología , Órgano Subfornical/fisiología , Sed/fisiología , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteínas de Unión al ADN/metabolismo , Deshidratación/fisiopatología , Ingestión de Líquidos , Agua Potable , Rayos Láser , Ratones , Optogenética , Respuesta de Saciedad , Factores de Transcripción/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismoRESUMEN
The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.
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Ganglio Geniculado/citología , Neuronas/fisiología , Percepción del Gusto/fisiología , Gusto/fisiología , Lengua/fisiología , Animales , Calcio/metabolismo , Ratones , Ratones Transgénicos , Papilas Gustativas/citología , Papilas Gustativas/fisiología , Lengua/citología , Lengua/inervaciónRESUMEN
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.
Asunto(s)
Cloruro de Sodio Dietético/farmacología , Papilas Gustativas/efectos de los fármacos , Papilas Gustativas/metabolismo , Gusto/efectos de los fármacos , Gusto/fisiología , Animales , Apetito/efectos de los fármacos , Apetito/genética , Apetito/fisiología , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Silenciador del Gen , Ratones , Ratones Noqueados , Mutación/genética , Fosfolipasa C beta/deficiencia , Fosfolipasa C beta/genética , Fosfolipasa C beta/metabolismo , Cloruro de Sodio Dietético/administración & dosificación , Canales Catiónicos TRPM/deficiencia , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Gusto/genética , Papilas Gustativas/citologíaRESUMEN
The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. We explored the logic of taste coding in the brain by examining how sweet, bitter, umami, and salty qualities are represented in the primary taste cortex of mice. We used in vivo two-photon calcium imaging to demonstrate topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.
Asunto(s)
Mapeo Encefálico , Corteza Cerebral/fisiología , Neuronas/fisiología , Gusto/fisiología , Vías Aferentes , Animales , Corteza Cerebral/citología , Cicloheximida , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Imagen Molecular , Cloruro de Sodio , Glutamato de Sodio , Edulcorantes , Papilas Gustativas/fisiologíaRESUMEN
The ability of insects to learn and navigate to specific locations in the environment has fascinated naturalists for decades. The impressive navigational abilities of ants, bees, wasps and other insects demonstrate that insects are capable of visual place learning, but little is known about the underlying neural circuits that mediate these behaviours. Drosophila melanogaster (common fruit fly) is a powerful model organism for dissecting the neural circuitry underlying complex behaviours, from sensory perception to learning and memory. Drosophila can identify and remember visual features such as size, colour and contour orientation. However, the extent to which they use vision to recall specific locations remains unclear. Here we describe a visual place learning platform and demonstrate that Drosophila are capable of forming and retaining visual place memories to guide selective navigation. By targeted genetic silencing of small subsets of cells in the Drosophila brain, we show that neurons in the ellipsoid body, but not in the mushroom bodies, are necessary for visual place learning. Together, these studies reveal distinct neuroanatomical substrates for spatial versus non-spatial learning, and establish Drosophila as a powerful model for the study of spatial memories.
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Drosophila melanogaster/fisiología , Aprendizaje/fisiología , Percepción Visual/fisiología , Animales , Encéfalo/citología , Encéfalo/fisiología , Condicionamiento Psicológico/fisiología , Señales (Psicología) , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Femenino , Vidrio , Locomoción/fisiología , Memoria/fisiología , Modelos Animales , Modelos Neurológicos , Cuerpos Pedunculados , Odorantes , Orientación/fisiología , Dióxido de Silicio , Temperatura , Factores de TiempoRESUMEN
Thermosensation is an indispensable sensory modality. Here, we study temperature coding in Drosophila, and show that temperature is represented by a spatial map of activity in the brain. First, we identify TRP channels that function in the fly antenna to mediate the detection of cold stimuli. Next, we identify the hot-sensing neurons and show that hot and cold antennal receptors project onto distinct, but adjacent glomeruli in the Proximal-Antennal-Protocerebrum (PAP) forming a thermotopic map in the brain. We use two-photon imaging to reveal the functional segregation of hot and cold responses in the PAP, and show that silencing the hot- or cold-sensing neurons produces animals with distinct and discrete deficits in their behavioral responses to thermal stimuli. Together, these results demonstrate that dedicated populations of cells orchestrate behavioral responses to different temperature stimuli, and reveal a labeled-line logic for the coding of temperature information in the brain.
Asunto(s)
Drosophila/fisiología , Animales , Encéfalo/fisiología , Frío , Proteínas de Drosophila/metabolismo , Calor , Células Receptoras Sensoriales/fisiología , Canales Catiónicos TRPP/metabolismo , Sensación TérmicaRESUMEN
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. 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. 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. 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. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCalpha 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.
Asunto(s)
Sodio/fisiología , Papilas Gustativas/fisiología , Gusto/genética , Animales , Conducta/fisiología , Canales Epiteliales de Sodio/genética , Canales Epiteliales de Sodio/metabolismo , Ratones , Ratones Transgénicos , Papilas Gustativas/citología , Papilas Gustativas/metabolismoRESUMEN
Carbonated beverages are commonly available and immensely popular, but little is known about the cellular and molecular mechanisms underlying the perception of carbonation in the mouth. In mammals, carbonation elicits both somatosensory and chemosensory responses, including activation of taste neurons. We have identified the cellular and molecular substrates for the taste of carbonation. By targeted genetic ablation and the silencing of synapses in defined populations of taste receptor cells, we demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO2 taste sensor. Together, these studies reveal the basis of the taste of carbonation as well as the contribution of taste cells in the orosensory response to CO2.