RESUMEN
Experimental or traumatic nerve injury causes the degeneration of associated taste buds. Unlike most sensory systems, the sectioned nerve and associated taste buds can then regenerate, restoring neural responses to tastants. It was previously unknown whether injury-induced immune factors mediate this process. The proinflammatory cytokines, interleukin (IL)-1α and IL-1ß, and their requisite receptor are strongly expressed by anterior taste buds innervated by the chorda tympani nerve. We tested taste bud regeneration and functional recovery in mice lacking the IL-1 receptor. After axotomy, the chorda tympani nerve regenerated but was initially unresponsive to tastants in both WT and Il1r KO mice. In the absence of Il1r signaling, however, neural taste responses remained minimal even >8 weeks after injury in both male and female mice, whereas normal taste function recovered by 3 weeks in WT mice. Failed recovery was because of a 57.8% decrease in regenerated taste buds in Il1r KO compared with WT axotomized mice. Il1a gene expression was chronically dysregulated, and the subset of regenerated taste buds were reinnervated more slowly and never reached full volume as progenitor cell proliferation lagged in KO mice. Il1r signaling is thus required for complete taste bud regeneration and the recovery of normal taste transmission, likely by impairing taste progenitor cell proliferation. This is the first identification of a cytokine response that promotes taste recovery. The remarkable plasticity of the taste system makes it ideal for identifying injury-induced mechanisms mediating successful regeneration and recovery.SIGNIFICANCE STATEMENT Taste plays a critical role in nutrition and quality of life. The adult taste system is highly plastic and able to regenerate following the disappearance of most taste buds after experimental nerve injury. Several growth factors needed for taste bud regeneration have been identified, but we demonstrate the first cytokine pathway required for the recovery of taste function. In the absence of IL-1 cytokine signaling, taste bud regeneration is incomplete, preventing the transmission of taste activity to the brain. These results open a new direction in revealing injury-specific mechanisms that could be harnessed to promote the recovery of taste perception after trauma or disease.
Asunto(s)
Papilas Gustativas , Masculino , Femenino , Ratones , Animales , Papilas Gustativas/fisiología , Gusto/fisiología , Axotomía , Calidad de Vida , Regeneración Nerviosa/fisiología , Nervio de la Cuerda del Tímpano/lesiones , Nervio de la Cuerda del Tímpano/fisiología , CitocinasRESUMEN
In behavioral experiments, rats perceive sodium carbonate (Na2CO3) as super salty. In fact, when the dissociated Na+ ions are accounted for, rats perceive Na2CO3 as 5× saltier than equinormal concentrations of NaCl. The chorda tympani nerve (CT) responds to salts through at least two receptor mechanisms and is a model system for understanding how salt taste is transmitted to the brain. Here, we recorded CT nerve activity to a broad range of NaCl (3-300 mM) and Na2CO3 (3-300 mN) to investigate why Na2CO3 tastes so salty to rats. Benzamil, a specific epithelial sodium channel (ENaC) antagonist, was used to determine the relative contribution of apical ENaCs in Na2CO3 transduction. The benzamil-insensitive component of CT nerve responses was enhanced by increasing the adapted tongue temperature from 23°C to 30°C. Na2CO3 solutions are alkaline, so we compared neural responses (with and without benzamil) to 100 mM NaCl alone (6.2 pH) and at a pH (11.2 pH) that matched 100 mN Na2CO3. As expected, NaCl responses increased progressively with increasing concentration and temperature. Responses to 3 mN Na2CO3 were greater than 3 mM NaCl with and without benzamil, but the shape of the first log-fold range of was relatively flat. Adjusting the pH of NaCl to 11.2 abolished the thermal enhancement of 100 mN NaCl through the benzamil-insensitive pathway. Rinsing Na2CO3 off the tongue resulted in robust aftertaste that was concentration dependent, thermally sensitive, and benzamil-insensitive. Responses to alkaline NaCl did not recapitulate Na2CO3 responses or aftertaste, suggesting multiple transduction mechanisms for the cations (2Na+) and anion (CO3-2).
Asunto(s)
Cloruro de Sodio , Gusto , Ratas , Animales , Cloruro de Sodio/farmacología , Ratas Sprague-Dawley , Gusto/fisiología , Nervio de la Cuerda del Tímpano/fisiología , Amilorida , DisgeusiaRESUMEN
Gustation and olfaction are integrated into flavor, which contribute to detection and identification of foods. We focused on the insular cortex (IC), as a possible center of flavor integration, because the IC has been reported to receive olfactory in addition to gustatory inputs. In the present report, we tested the hypothesis that these two chemosensory signals are integrated in the IC. We examined the spatiotemporal dynamics of cortical responses induced by stimulating the chorda tympani nerve (CT) and the main olfactory bulb (mOB) in male Sprague-Dawley rats by in vivo optical imaging with a voltage-sensitive dye (VSD). CT stimulation elicited responses in the rostral part of the dysgranular IC (DI), while responses to mOB stimulation were observed in the agranular IC (AI) as well as in the piriform cortex (PC). To characterize the temporal specificity of these responses, we performed combined mOB and CT stimulation with three different timings: simultaneous stimulation and the stimulation of the mOB 150 ms before or after CT stimulation. Simultaneous stimulation increased the signal amplitude in AI additively. These results indicate that the AI and DI contribute to the convergence of gustatory and olfactory information. Of them the DI predominantly processes the taste information, whereas the AI is more sensitive to the olfactory signal.
Asunto(s)
Corteza Cerebral/fisiología , Nervio de la Cuerda del Tímpano/fisiología , Bulbo Olfatorio/fisiología , Gusto/fisiología , Animales , Estimulación Eléctrica/métodos , Masculino , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Olfato/fisiología , Percepción del Gusto/fisiologíaRESUMEN
Studies have suggested that communication between taste cells shapes the gustatory signal before transmission to the brain. To further explore the possibility of intragemmal signal modulation, we adopted an optogenetic approach to stimulate sour-sensitive (Type III) taste cells using mice expressing Cre recombinase under a specific Type III cell promoter, Pkd2l1 (polycystic kidney disease-2-like 1), crossed with mice expressing Cre-dependent channelrhodopsin (ChR2). The application of blue light onto the tongue allowed for the specific stimulation of Type III cells and circumvented the nonspecific effects of chemical stimulation. To understand whether taste modality information is preprocessed in the taste bud before transmission to the sensory nerves, we recorded chorda tympani nerve activity during light and/or chemical tastant application to the tongue. To assess intragemmal modulation, we compared nerve responses to various tastants with or without concurrent light-induced activation of the Type III cells. Our results show that light significantly decreased taste responses to sweet, bitter, salty, and acidic stimuli. On the contrary, the light response was not consistently affected by sweet or bitter stimuli, suggesting that activation of Type II cells does not affect nerve responses to stimuli that activate Type III cells.
Asunto(s)
Optogenética , Gusto/fisiología , Animales , Canales de Calcio/genética , Canales de Calcio/metabolismo , Channelrhodopsins/genética , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Nervio de la Cuerda del Tímpano/efectos de la radiación , Luz , Ratones , Ratones Transgénicos , Regiones Promotoras Genéticas , Quinina/química , Quinina/farmacología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Estimulación Química , Sacarosa/química , Sacarosa/farmacologíaRESUMEN
OBJECTIVES: To investigate the relationships among four different gustatory function tests in healthy young adults: electrogustometry (EGM), filter paper disk (FPD), whole-mouth, and taste strip methods. The relationships of the results of gustatory function tests with salivary flow rate were also investigated. METHODS: Sixty healthy young adults (30 men, 26.9 ± 4.7 years; 30 women, 25.7 ± 4.6 years) who did not have disorders or conditions related with gustatory function were included. Four different gustatory function tests using the EGM, FPD, whole-mouth, and taste strip methods were performed in each participant with 2- to 3-day intervals between tests. The flow rates of unstimulated and stimulated whole saliva were measured. RESULTS: There were no significant differences between sexes in all the examined gustatory function tests. The levels of correlations between the gustatory function tests were low. The EGM threshold correlated with the taste score of the FPD method in the chorda tympani nerve area. Different chemical gustatory function tests did not correlate significantly in any of the four taste qualities. Salivary flow rates did not correlate with taste perception. CONCLUSIONS: The correlations between gustatory function tests were weak. A significant correlation was found between the results of EGM and FPD methods in the chorda tympani nerve area.
Asunto(s)
Nervio de la Cuerda del Tímpano/fisiología , Salivación , Umbral Gustativo , Gusto , Adulto , Femenino , Humanos , Masculino , Boca , Percepción del Gusto , Adulto JovenRESUMEN
Sugar-sweetened beverages are the major source of added calories in the Western diet and their prevalence is associated with obesity and metabolic disruption. Despite the critical role of the taste system in determining food selection and consumption, the effects of chronic sucrose consumption on the peripheral taste system in mammals have received limited attention. We offered female Sprague Dawley rats free access to water and one of three diets for up to 40 days: (1) sucrose-free chow or "NS" diet; (2) a high-sucrose dry diet or "HS"; or (3) 30% sucrose solution and the NS diet, designated "LiqS" diet. Sucrose consumption by LiqS rats gradually increased and by day 14 was equal to that of HS rats. Food intake decreased in LiqS rats, but their energy intake remained higher than for NS or HS rats. There was no significant difference in weight gain of the groups during the study. Recordings from the chorda tympani nerve (CT), which innervates taste buds on the anterior tongue, revealed decreased responses to 1â¯M sucrose in both LiqS and HS rats and to acesulfame K and salt tastants in LiqS rats after 40 days on diet. Umami, bitter, and acid response magnitudes were unchanged in both groups. These results demonstrate that chronic sucrose exposure inhibits taste responses to higher concentrations of sweet stimuli. More surprisingly, CT responses to NaCl and 0.5M NaAc were significantly reduced in rats on the LiqS diet. Thus, the physical form of the diet influences taste responsiveness to salt and sweet taste function. These data suggest that taste buds are previously unappreciated targets of chronic sucrose consumption.
Asunto(s)
Sacarosa en la Dieta/administración & dosificación , Gusto/efectos de los fármacos , Animales , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Fenómenos Electrofisiológicos , Ingestión de Energía , Femenino , Preferencias Alimentarias/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Soluciones , Gusto/genética , Papilas Gustativas/efectos de los fármacos , Papilas Gustativas/fisiología , Aumento de Peso/efectos de los fármacosRESUMEN
Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2-10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data. NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.
Asunto(s)
Potenciales de Acción , Modelos Neurológicos , Neuronas/fisiología , Núcleo Solitario/fisiología , Vías Aferentes/fisiología , Animales , Nervio de la Cuerda del Tímpano/fisiología , Neuronas GABAérgicas/fisiología , Ratones Transgénicos , Vías Nerviosas/fisiología , Gusto/fisiologíaRESUMEN
Upon presentation of a calorically dense diet, rats display hyperphagia driven by increased meal size. The increased meal size and hyperphagia are most robust across the first several days of diet exposure before changes in body weight are evident, thus it is plausible that one of the factors that drives the hyperphagia may be enhanced orosensory responsivity. Here, electrophysiological responses to an array of taste stimuli were recorded from the chorda tympani nerve, a branch of the facial nerve that innervates taste receptors in the anterior tongue, of rats presented a high-energy (45% fat and 17% sucrose) diet for 3 days. Responses in the high-energy diet group were significantly higher for 0.01, 0.03, 0.06 and 0.3 M sucrose; 0.05 M Na-saccharin; and 0.01 M quinine compared with those of chow-fed controls. Another cohort of animals was tested in 30-min brief-access taste sessions (10-s trials) to a sucrose concentration series across the first 6 days of high-energy diet presentation. Both groups responded in a concentration-dependent manner. No significant group differences in unconditioned licking or trials initiated were revealed. Results from a third cohort of rats showed that responses to sucrose in a brief-access taste test also remained largely unchanged as a function of 3-day access to a sucrose solution. Taken together, these findings suggest that 3 days of high-energy diet exposure results in alterations to peripheral gustatory signaling yet these changes do not necessarily generalize to changes in responsiveness to sucrose, as least as measured in this procedure.
Asunto(s)
Alimentación Animal/análisis , Nervio de la Cuerda del Tímpano/fisiología , Dieta/veterinaria , Conducta Alimentaria , Sacarosa , Animales , Ingestión de Energía , Preferencias Alimentarias , Masculino , Ratas , Ratas Sprague-Dawley , GustoRESUMEN
Sensory processing is susceptible to decline with age. The sense of taste is, however, generally thought to be resistant to aging. We investigated how chorda-tympani nerve responses and fungiform-taste pores are affected by aging in the Sprague-Dawley rat, a model system for salt taste. First, we measured chorda-tympani nerve responses to NH4Cl and NaCl solutions in young (3-5 months old) and aged (14-15 months old) rats. Aged rats had significantly attenuated chorda-tympani responses to 0.01, 0.03, 0.1, and 0.3 M NaCl, whereas responses to NH4Cl were statistically similar between age groups. Second, we investigated if fungiform papillae, which harbor taste buds innervated by the chorda-tympani nerve, were affected by aging in "young" (4-7 months old) and "aged" ("aged1" 18 months old and "aged2" 24-28 months old) rats. Using scanning electron microscopy, we found that aging significantly reduced morphological characteristics associated with intact fungiform-taste pores (hillock, rim, pore presence, and open pore). We conclude that the structure and function of the peripheral-taste system may not be as resistant to aging as previously reported.
Asunto(s)
Envejecimiento/fisiología , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Cloruro de Sodio/farmacología , Papilas Gustativas/efectos de los fármacos , Gusto/fisiología , Factores de Edad , Animales , Microscopía Electrónica de Rastreo , Modelos Animales , Ratas Sprague-Dawley , Papilas Gustativas/fisiología , Papilas Gustativas/ultraestructuraRESUMEN
In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium.
Asunto(s)
Nervio de la Cuerda del Tímpano/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Canales Epiteliales de Sodio/metabolismo , Cloruro de Sodio/farmacología , Sed/fisiología , Amilorida/análogos & derivados , Amilorida/farmacología , Animales , Bloqueadores del Canal de Sodio Epitelial/farmacología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Afferent chorda tympani (CT) fibers innervating taste and somatosensory receptors in fungiform papillae have neuron cell bodies in the geniculate ganglion (GG). The GG/CT fibers branch in the tongue to innervate taste buds in several fungiform papillae. To investigate receptive field characteristics of GG/CT neurons, we recorded extracellular responses from GG cells to application of chemical and thermal stimuli. Receptive field size was mapped by electrical stimulation of individual fungiform papillae. Response latency to electrical stimulation was used to determine fiber conduction velocity. Responses of GG neurons to lingual application of stimuli representing four taste qualities, and water at 4°C, were used to classify neuron response properties. Neurons classified as SALT, responding only to NaCl and NH4Cl, had a mean receptive field size of six papillae. Neurons classified as OTHER responded to salts and other chemical stimuli and had smaller mean receptive fields of four papillae. Neurons that responded to salts and cold stimuli, classified as SALT/THERMAL, and neurons responding to salts, other chemical stimuli and cold, classified as OTHER/THERMAL, had mean receptive field sizes of six and five papillae, respectively. Neurons responding only to cold stimuli, categorized as THERMAL, had receptive fields of one to two papillae located at the tongue tip. Based on conduction velocity most of the neurons were classified as C fibers. Neurons with large receptive fields had higher conduction velocities than neurons with small receptive fields. These results demonstrate that GG neurons can be distinguished by receptive field size, response properties and afferent fiber conduction velocity derived from convergent input of multiple taste organs.
Asunto(s)
Nervio de la Cuerda del Tímpano/fisiología , Ganglio Geniculado/citología , Conducción Nerviosa/fisiología , Neuronas/fisiología , Células Receptoras Sensoriales/fisiología , Potenciales de Acción/fisiología , Cloruro de Amonio/farmacología , Análisis de Varianza , Animales , Estimulación Eléctrica , Femenino , Conducción Nerviosa/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción , Células Receptoras Sensoriales/efectos de los fármacos , Cloruro de Sodio/farmacología , Estimulación Química , Gusto/fisiología , Papilas Gustativas/fisiologíaRESUMEN
Five fundamental taste qualities (sweet, bitter, salty, sour, umami) are sensed by dedicated taste cells (TCs) that relay quality information to gustatory nerve fibers. In peripheral taste signaling pathways, ATP has been identified as a functional neurotransmitter, but it remains to be determined how specificity of different taste qualities is maintained across synapses. Recent studies demonstrated that some gut peptides are released from taste buds by prolonged application of particular taste stimuli, suggesting their potential involvement in taste information coding. In this study, we focused on the function of glucagon-like peptide-1 (GLP-1) in initial responses to taste stimulation. GLP-1 receptor (GLP-1R) null mice had reduced neural and behavioral responses specifically to sweet compounds compared to wild-type (WT) mice. Some sweet responsive TCs expressed GLP-1 and its receptors were expressed in gustatory neurons. GLP-1 was released immediately from taste bud cells in response to sweet compounds but not to other taste stimuli. Intravenous administration of GLP-1 elicited transient responses in a subset of sweet-sensitive gustatory nerve fibers but did not affect other types of fibers, and this response was suppressed by pre-administration of the GLP-1R antagonist Exendin-4(3-39). Thus GLP-1 may be involved in normal sweet taste signal transmission in mice.
Asunto(s)
Péptido 1 Similar al Glucagón/metabolismo , Transducción de Señal , Papilas Gustativas/metabolismo , Gusto , Amilorida/farmacología , Animales , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Ensayo de Inmunoadsorción Enzimática , Exenatida , Receptor del Péptido 1 Similar al Glucagón , Ácido Clorhídrico/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Microscopía Confocal , Neuronas/metabolismo , Neuronas/fisiología , Péptidos/farmacología , Quinina/farmacología , Receptores de Glucagón/deficiencia , Receptores de Glucagón/genética , Sacarina/farmacología , Cloruro de Sodio/farmacología , Sacarosa/farmacología , Papilas Gustativas/citología , Papilas Gustativas/fisiología , Ponzoñas/farmacologíaRESUMEN
Taste buds are unusual in requiring ATP as a transmitter to activate sensory nerve fibers. In response to taste stimuli, taste cells release ATP, activating purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside triphosphate previously identified as nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in the function of taste buds by examining gene-targeted Entpd2-null mice globally lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme histochemistry reveals no reaction product in taste buds of knockout mice, suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and immunocytochemistry demonstrated that in knockout mice all cell types are present in taste buds, even those cells normally expressing NTPDase2. In addition, the overall number and size of taste buds are normal in Entpd2-null mice. Luciferin/luciferase assays of circumvallate tissue of knockout mice detected elevated levels of extracellular ATP. Electrophysiological recordings from two taste nerves, the chorda tympani and glossopharyngeal, revealed depressed responses to all taste stimuli in Entpd2-null mice. Responses were more depressed in the glossopharyngeal nerve than in the chorda tympani nerve and involved all taste qualities; responses in the chorda tympani were more depressed to sweet and umami stimuli than to other qualities. We suggest that the excessive levels of extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors associated with nerve fibers, thereby depressing taste responses.
Asunto(s)
Adenosina Trifosfatasas/metabolismo , Papilas Gustativas/enzimología , Papilas Gustativas/fisiología , Gusto/fisiología , Adenosina Trifosfatasas/genética , Adenosina Trifosfato/metabolismo , Análisis de Varianza , Animales , Nervio de la Cuerda del Tímpano/fisiología , Expresión Génica , Nervio Glosofaríngeo/fisiología , Inmunohistoquímica , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Papilas Gustativas/metabolismoRESUMEN
KEY POINTS: Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor deficient (db/db) and diet-induced obese (DIO) mice. Chorda tympani (CT) nerve responses of lean mice to sweet compounds were increased after administration of leptin antagonist (LA) but not affected by administration of cannabinoid receptor antagonist (AM251). db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid levels in the taste organ, and enhanced expression of a biosynthesizing enzyme of endocannabinoids in taste cells. The effect of LA was gradually decreased and that of AM251 was increased during the course of obesity in DIO mice. These findings suggest that circulating leptin, but not local endocannabinoids, is a dominant modulator for sweet taste in lean mice and endocannabinoids become more effective modulators of sweet taste under conditions of deficient leptin signalling. ABSTRACT: Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1 : AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2-arachidonoyl-sn-glycerol (2-AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2-AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue.
Asunto(s)
Endocannabinoides/fisiología , Leptina/fisiología , Obesidad/fisiopatología , Gusto/fisiología , Animales , Ácidos Araquidónicos/fisiología , Nervio de la Cuerda del Tímpano/fisiología , Femenino , Glicéridos/fisiología , Leptina/sangre , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Papilas Gustativas/fisiologíaRESUMEN
KEY POINTS: The taste receptor T1R1 + T1R3 heterodimer and metabotropic glutamate receptors (mGluR) may function as umami taste receptors. Here, we used mGluR4 knockout (mGluR4-KO) mice and examined the function of mGluR4 in peripheral taste responses of mice. The mGluR4-KO mice showed reduced responses to glutamate and L-AP4 (mGluR4 agonist) in the chorda tympani and glossopharyngeal nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were suppressed by gurmarin (T1R3 blocker) and AIDA (group I mGluR antagonist). The present study not only provided functional evidence for the involvement of mGluR4 in umami taste responses, but also suggested contributions of T1R1 + T1R3 and mGluR1 receptors in glutamate responses. ABSTRACT: Umami taste is elicited by L-glutamate and some other amino acids and is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heterodimers of taste receptor type 1, members 1 and 3 (T1R1 + T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Accumulated evidences support the involvement of T1R1 + T1R3 in umami responses in mice. However, little is known about the in vivo function of mGluR in umami taste. Here, we examined taste responses of the chorda tympani (CT) and the glossopharyngeal (GL) nerves in wild-type mice and mice genetically lacking mGluR4 (mGluR4-KO). Our results indicated that compared to wild-type mice, mGluR4-KO mice showed significantly smaller gustatory nerve responses to glutamate and L-(+)-2-amino-4-phosphonobutyrate (an agonist for group III mGluR) in both the CT and GL nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were not affected by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (an antagonist for group III mGluR), but were suppressed by gurmarin (a T1R3 blocker) in the CT and (RS)-1-aminoindan-1,5-dicarboxylic acid (an antagonist for group I mGluR) in the CT and GL nerve. In wild-type mice, both quisqualic acid (an agonist for group I mGluR) and L-(+)-2-amino-4-phosphonobutyrate elicited gustatory nerve responses and these responses were suppressed by addition of (RS)-1-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-cyclopropyl-4-phosphonophenylglycine, respectively. Collectively, the present study provided functional evidences for the involvement of mGluR4 in umami taste responses in mice. The results also suggest that T1R1 + T1R3 and mGluR1 are involved in umami taste responses in mice. Thus, umami taste would be mediated by multiple receptors.
Asunto(s)
Nervio de la Cuerda del Tímpano/fisiología , Nervio Glosofaríngeo/fisiología , Receptores Acoplados a Proteínas G/fisiología , Receptores de Glutamato Metabotrópico/fisiología , Gusto/fisiología , Animales , Femenino , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Glutamato Metabotrópico/genética , Lengua/inervación , Lengua/fisiologíaRESUMEN
The peripheral taste system of the adult rodent is highly resilient against damage, with morphological, behavioral, and functional recovery evident after regeneration of a transected nerve. If chorda tympani transection (CTX) occurs at early postnatal ages however, the nerve fails to regenerate and effects on tongue morphology and behavior are more severe and longer-lasting compared to adult denervation. To examine whether neonatal CTX induces functional changes in intact nerves, whole-nerve electrophysiology was performed on the glossopharyngeal (GL) and chorda tympani (CT) nerves of adult rats that received CTX at P10. Attenuation of NaCl-elicited GL responses were observed in CTX rats 2 months after surgery, with bilateral denervation causing the largest decreases in responses. When assessed 1 year after neonatal CTX, amiloride-sensitive responses to NaCl in the contralateral CT increased while amiloride-insensitive responses decreased. Responses to other tastants were consistent with control animals. This is the first evidence of long-term functional changes to the peripheral taste system after injury in rats fed a normal diet. This study further characterizes the developing peripheral taste system as highly susceptible to change following neural injury.
Asunto(s)
Cloruro de Amonio/farmacología , Nervio de la Cuerda del Tímpano/fisiología , Nervio Glosofaríngeo/fisiología , Cloruro de Sodio/farmacología , Gusto/fisiología , Animales , Animales Recién Nacidos , Nervio de la Cuerda del Tímpano/cirugía , Desnervación , Electrofisiología/métodos , Femenino , Sistema Nervioso Periférico/fisiología , Ratas Sprague-Dawley , Lengua/efectos de los fármacos , Lengua/fisiologíaRESUMEN
Modulatory effects of pHi and [Ca(2+)]i on taste receptor cell (TRC) epithelial sodium channel (ENaC) were investigated by monitoring chorda tympani (CT) responses to NaCl and KCl at various lingual voltages, before and after lingual application of ionomycin and with 0-10mM CaCl2 in the stimulus and rinse solutions adjusted to pHo 2.0-9.7. 0.1 and 0.5M KCl responses varied continuously with voltage and were fitted to an apical ion channel kinetic model using the same parameters. ENaC-dependent NaCl CT response was fitted to the same channel model but with parameters characteristic of ENaC. A graded increase in TRC [Ca(2+)]i decreased the ENaC-dependent NaCl CT response, and inhibited and ultimately eliminated its pH sensitivity. CT responses to KCl were pHi- and [Ca(2+)]i-independent. Between ±60 mV applied lingual potential, the data were well described by a linear approximation to the nonlinear channel equation and yielded 2 parameters, the open-circuit response and the negative of the slope of the line in the CT response versus voltage plot, designated the response conductance. The ENaC-dependent NaCl CT response conductance was a linear function of the open-circuit response for all pHi-[Ca(2+)]i combinations examined. Analysis of these data shows that pHi and [Ca(2+)]i regulate TRC ENaC exclusively through modulation of the maximum CT response.
Asunto(s)
Calcio/metabolismo , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Cloruro de Potasio/farmacología , Cloruro de Sodio/farmacología , Algoritmos , Animales , Nervio de la Cuerda del Tímpano/fisiología , Electrodos , Canales Epiteliales de Sodio/metabolismo , Femenino , Concentración de Iones de Hidrógeno , Iones/química , Técnicas de Placa-Clamp , Protones , Ratas , Ratas Sprague-DawleyRESUMEN
Different parts of the mouth vary in their taste responsiveness and gustatory transduction components. However, there have been few attempts to consider regional variation among areas innervated by a single nerve branch or containing only one type of gustatory papilla. Here, we examined whether taste-elicited responses of a single nerve, the chorda tympani (CT), depend on where taste solutions are delivered on the tongue in mice. In experiment 1, multiunit CT responses to NaCl and sucrose were larger if sapid taste solutions were applied to the tongue tip, which contains the anterior-most fungiform papillae, than if they were flowed over fungiform and foliate papillae on the posterior tongue. Further, the epithelial sodium channel (ENaC) blocker amiloride suppressed NaCl responses to a greater degree for the tongue tip. In experiment 2, CT nerve responses were compared between the tongue tip and a region further back that contained only fungiform papillae. NaCl and sucrose solutions applied to posterior fungiform papillae produced smaller responses than did those elicited by the same taste stimuli applied to anterior fungiform papillae on the tongue tip. Amiloride suppressed the response to NaCl delivered to the anterior fungiform but not posterior fungiform papillae. These results indicate that the CT response is tongue-region dependent in the mouse. Furthermore, the spatial location of a fungiform papilla provides important information about its properties, such as whether sodium taste transduction is mediated by amiloride-sensitive ENaCs.
Asunto(s)
Nervio de la Cuerda del Tímpano/fisiología , Gusto/fisiología , Lengua/fisiología , Amilorida/farmacología , Animales , Nervio de la Cuerda del Tímpano/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos A , Ratones Endogámicos C57BL , Cloruro de Sodio/farmacología , Sacarosa/farmacología , Gusto/efectos de los fármacos , Lengua/efectos de los fármacosRESUMEN
Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases.
Asunto(s)
Quinina , Percepción del Gusto/fisiología , Gusto/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Conducta Animal/fisiología , Nervio de la Cuerda del Tímpano/fisiología , Ácido Cítrico , Femenino , Inosina Monofosfato , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sacarina , Cloruro de Sodio , Glutamato de Sodio , Papilas Gustativas/citología , Papilas Gustativas/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Taste system is a perfect system to study degeneration and regeneration after nerve injury because the taste system is highly plastic and the regeneration is robust. Besides, degeneration and regeneration can be easily measured since taste buds arise in discrete locations, and nerves that innervate them can be accurately quantified. Neurotrophins are a family of proteins that regulate neural survival, function, and plasticity after nerve injury. Recent studies have shown that neurotrophins play an important role in the developmental and mature taste system, indicating neurtrophin might also regulate taste system following gustatory nerve injury. This review will summarize how taste system degenerates and regenerates after gustatory nerve cut and conclude potential roles of neurotrophin in regulating the process.