Chemical Senses最新文献

Several forebrain areas project to the rostral gustatory portion of the nucleus of the solitary tract (rNST), where they modulate processing of oral gustatory signals. Among them, the central nucleus of the amygdala (CeA) provides descending input via somatostatin-expressing (Sst) neurons, where suppression of CeA/Sst-to-rNST neural activity alters ingestion of the bitter tastant quinine. Together, these results indicate that the regulation of ingestive behavior involves descending neuromodulatory processes. Yet, the postsynaptic targets of CeA/Sst and non-Sst-expressing neurons in rNST, as well as the projection targets of rNST neurons receiving CeA input, remain unknown. Using a combination of transmission electron microscopy and transsynaptic viral tracing in transgenic mice, we show that CeA axon terminals in the rNST are GABAergic and form synapses with Phox2b-, glutamate-, calretinin-, and GABA-expressing neurons in distinct proportions. rNST neurons receiving CeA input were distributed across the medial, central, and ventral subdivisions and projected primarily to the ipsilateral reticular formation and parabrachial nucleus. These findings suggest that CeA input to rNST neurons influences both ascending gustatory information and orosensory motor functions, including licking, mastication, and salivation.

Most mammals detect important specific chemicals such as pheromones via the vomeronasal system (VNS). The types-1 (V1R) and -2 (V2R) families of vomeronasal receptors detect volatile and water-soluble substances, respectively, and couple with G protein α subunits i2 (Gαi2) and o (Gαo), respectively. The V1R/Gαi2- and V2R/Gαo-neurons in the vomeronasal organ (VNO), respectively project to the anterior and posterior halves of the accessory olfactory bulb (AOB) (i.e. segregated type) in rodents and some other mammalian species. In contrast, the VNO in most species in the Laurasiatheria clade contains only V1R/Gαi2-neurons that project to the entire AOB (i.e. uniform type). Considering the above, the posterior pathway for identifying specific emitters via the V2R families might have disappeared from the Laurasiatheria clade. Here, we analyzed the VNS of hedgehogs, one of the earliest divergent groups in the Laurasiatheria clade. In the African pigmy hedgehog (Atelerix albiventris), immunohistochemical staining using antibodies against Gαi2 and Gαo revealed that the VNO contains V1R/Gαi2- and V2R/Gαo-neurons. The vomeronasal nerve and glomerular layers of the hedgehog AOB were positive for Gαi2, and the posterior half was also positive for Gαo. This profile is intermediate between the segregated and uniform types of the mammalian VNS. Dual immunofluorescence staining also indicated that the posterior glomeruli of the hedgehog AOB comprised mixtures of V1R/Gαi2- and V2R/Gαo-axons. These features of the hedgehog VNS seem to reflect the process of evolutionary disappearance of V2R-pathway within Laurasiatheria.

Taste in Drosophila melanogaster is crucial to survival, influencing feeding, mating, and egg-laying behaviors. Taste organs are located on various parts of the body, including the legs, proboscis, wings, and ovipositor. Taste neurons detect chemicals via receptors like gustatory receptors, ionotropic receptors, and transient receptor potentials, with bitter and sweet tastes linked to specific neurons (Gr66a+ and Gr5a+). Bitter substances such as caffeine activate neurons, resulting in rejection behavior. TrpA1 channels, associated with aversive responses, are involved in complex behaviors and could interact with taste receptors. Our results show that caffeine mixed with sucrose reduces proboscis extension in flies compared to sucrose alone, a response that requires only the TrpA1-E isoform out of the 5 possible ones. Furthermore, our data demonstrate that this avoidance requires TrpA1 and signaling via phospholipase C and inositol trisphosphate receptors in adult Gr66a+ neurons.

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canadian immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were 5 medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and 4 other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for 2 of the 5 drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in 1 bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (P = 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (P = 2.6e-8, P = 7.9e-11, respectively). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.

Attempts to map odor percepts to physical and chemical parameters have a long and challenging history. In contrast to color vision, where three classes of photoreceptors respond to the same stimulus property (wavelength), ~400 classes of olfactory receptors are available to respond in a non-linear non-additive fashion to ~5000 different chemical parameters. Theoretically, millions of permutations between structural elements of chemicals and their smells are possible, and some chemicals with different structures have the same odor and vice versa. Importantly, the same odor quality can come from multiple environmental objects and most odors depend upon the synthesis of a complex melody of volatile chemicals that individually can have dissimilar smells. At the individual receptor level, both agonists and antagonists within a mixture can impact receptor function. Hence, it is perhaps not surprising that no universal relationship between odor quality and underlying physical or chemical dimensions analogous to spectral wavelength for vision or air pressure waves for hearing has yet been identified. This review provides a historical account of psychological odor categorization, attempts to map odor percepts to physiochemical parameters, and attendant pitfalls. It concludes that perceived odor qualities may be best viewed as cognitive constructs with attendant variability due to individual experiences, linguistic processes, and biologic factors that do not map well to universal physiochemical dimensions.

We present a new method for fully self-administered olfactory testing. Technical development and testing and 2 user studies were conducted to test the functionality of a prototype device called Automated Olfactory Threshold Test (AutomOT). Technical testing showed repeatable functioning of the developed olfactory display technology in accurately producing 11 predefined odor intensity levels over 10 different days. In User Study 1, we tested the reliability, usability, and subjective workload of the use of the device. Participants (N = 29) with a normal sense of smell performed an automated threshold test 4 times. The results showed that the correlations between the tests were statistically significant, r = 0.44 to 0.78, all P-values ≤0.018. In User Study 2, we demonstrated the functioning of the device with normosmic and hyposmic/anosmic participants (n = 23 and n = 27, respectively) who performed both the current clinical standard, Sniffin' Sticks test, and the AutomOT test. Also, the usability and subjective workload of the use of the device were evaluated. The overall correlation of olfactory thresholds between the Sniffin' Sticks and the AutomOT was r = 0.48, P < 0.001. In both user studies, the results indicated good usability as measured by the System Usability Scale and low workload assessed by NASA Task Load Index. Overall, the results suggest that the newly developed AutomOT test is a reliable, valid, and usable tool for clinical assessment of olfactory thresholds.

Liking and disgust are the primary positive and negative emotions, respectively, and are crucial for nutrient intake and toxin avoidance. These emotions are induced by multimodal stimuli, such as taste, olfactory, and somatosensory inputs, and their dysregulation is evident in various psychiatric disorders. To understand the biological basis of liking and disgust, it is crucial to establish an animal model that allows for quantitative estimation of liking and disgust in response to multimodal stimuli. The only readout shared by many species, including humans, for liking and disgust, has been taste reactivity. However, readouts of non-taste stimuli-induced emotions remain unestablished. Here, we show that intraoral administration of capsaicin, a chemosomatosensory stimulus, elicits orofacial and bodily reactions in male mice similar to those observed in taste reactivity. Capsaicin-induced liking reactions at low concentrations and disgust reactions at high concentrations. Capsaicin-induced disgust reactions consisted of various reactions, including gape and forelimb flail, with the proportion of each reaction among the disgust reactions being similar to that induced by bitter and sour stimuli. These findings indicate that orofacial and bodily reactions, defined as taste reactivity, are elicited not only by taste stimuli but also by intraoral chemosomatosensory stimuli. Understanding the biological basis of capsaicin-induced orofacial and bodily reactions will advance our understanding of the fundamental mechanisms underlying liking and disgust across sensory modalities.

In mammals, olfactory communication between conspecifics is crucial in modulating reproductive function. In anestrous does (i.e. female goats), exposure to hair from sexually active bucks (SAB, i.e. male goats) triggers a luteinizing hormone response that may induce ovulation, the "male effect." However, the chemicals in buck hair responsible for this effect and the sensory pathways used by the females to detect this information remain insufficiently understood. In this study, we investigated whether sensory cells from the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) of does respond differently to olfactory stimuli from SAB versus wethers (CAS, i.e. castrated bucks) and how this response is influenced by the female reproductive status (breeding season, anestrous, or ovariectomized (OVX)). To explore this possibility, we stimulated freshly dissociated cells of MOE and VNO cells with chloroform/methanol and aqueous extractions from buck hair, and we assessed cell activation using calcium imaging. Regardless of the extraction method, we observed more cells activated by SAB hair compounds than by those from CAS males. More MOE cells from anestrous were activated by both chloroform and aqueous extracts from SAB than MOE cells from breeding season, or OVX does. Most of these responses originated from non-mature olfactory neurons. These findings suggest that females can discriminate buck sexual activity through sensory detection by the MOE and VNO. The increased response in the MOE to SAB hair compounds during the anestrous period suggests that the MOE may play a more significant role in the "male effect" during this period.

Mice are commonly used for laboratory research, due in large part to the widespread advancement in the genetic toolbox, such as reporters, knock-in, and knockout mice. The effects of aging on the taste system in mice have been largely unstudied. The aim of this study was to examine whether taste preferences to sucrose, NaCl, and NH4Cl were associated with aging and changes in ultrastructural characteristics of fungiform taste pores using scanning electron microscopy. Thirty-minute 2-bottle preference tests in wild-type mice indicated that preferences for NaCl and NH4Cl, but not sucrose, were significantly different in aged mice (16 to 17 months old) relative to young mice (5 months old). In the same animals, we found that the percentage of fungiform papilla with taste pores present was significantly reduced in the aged group. These findings are consistent with our recent study in rats, where aging had a significant impact on chorda tympani nerve responses to salt and ultrastructural characteristics of fungiform taste pores. Collectively, these data suggest that aging significantly affects fungiform taste pore morphology and has a significant impact on taste processing. Future studies investigating the factors that form and maintain taste pores are of critical importance as the pore is necessary for taste stimuli access to taste bud cells.

The mammalian olfactory system enables the detection of a wide variety of chemical compounds via the expression of a repertoire of olfactory receptors comprising the largest gene family in the mammalian genome. Olfactory sensory neurons (OSNs) each express only 1 odorant receptor (OR) gene. In mice, this requires activation of 1 OR gene and repression of over 1,400 other OR genes. In this review, we describe the mechanisms that support the transcription of OR genes and how these mechanisms impact which OR is expressed in each neuron. First, we discuss what is currently known about the role of transcription in OR choice. We then describe the role of specific features of OR genes and enhancers in the regulation of OR transcription. Finally, we discuss characteristics of OSNs which specify transcription of some OR genes while restricting the transcription of others.