Chemical Senses最新文献

Anxious adults show changes in smell function that are consistent with a durable shift in sensitivity toward particular odorants and away from others. Little is known regarding the development of these changes, including whether they exist in youth, are stable during the transition from childhood to adolescence, and whether odorant properties (e.g. trigeminal features, hedonic valence) affect anxiety-related differences in detection. To address this, we measured smell detection thresholds to phenyl ethyl alanine (PEA), a rose-like odorant with little trigeminal properties, and guaiacol (GUA), a smoke-like odorant with high trigeminal properties. These thresholds were measured at baseline and after an acute stress challenge, the Trier Social Stress Tests, in 131 healthy youth (in 4th, 7th, and 10th grades, age 9-16 years) that reported normal to elevated levels of anxiety. At baseline, high anxious youth exhibited heightened sensitivity to GUA coupled with reduced sensitivity to PEA, as well as a further exaggeration of this bias with acute stress. Importantly, sex, age, and hedonic valence moderated the relationship between trait anxiety and sensitivity to both odorants. Smell function and its aberrations are often overlooked in the literature on biomarkers of stress and anxiety. Taken together with the extant literature, these findings suggest that greater attention is warranted to characterize potential novel olfactory therapeutic targets-across the lifespan.

Due to the complex stimulation methods required, olfaction and touch are 2 relatively understudied senses in the field of perceptual (neuro-)science. In order to establish a consistent presentation method for the bimodal stimulation of these senses, we combined an olfactometer with the newly developed Unimodal Tactile Stimulation Device. This setup allowed us to study the influence of olfaction on tactile perception and opened up an unexplored field of research by examining the crossmodal influence of tactile stimuli on olfaction. Using a pseudorandomized design, we analyzed how positive or negative tactile and olfactory stimuli influenced the opposing modality's perceived intensity and pleasantness. By asking participants to rate tactile stimuli, we were able to reproduce previously reported differences indicating that bimodal presentation with an olfactory stimulus increases or reduces perceived tactile pleasantness in an odor-dependent manner while highlighting that this effect appears unique to women. Furthermore, we found the first evidence for the influence of tactile stimuli on perceived odor pleasantness, an effect that is also driven primarily by women in our study. Based on these findings we believe that future neurophysiological studies, using controlled stimulus presentation can help unravel how and why olfactory and tactile perception interact in the human brain.

Olfactory sensory neurons (OSNs) are bipolar neurons, unusual because they turn over continuously and have a multiciliated dendrite. The extensive changes in gene expression accompanying OSN differentiation in mice are largely known, especially the transcriptional regulators responsible for altering gene expression, revealing much about how differentiation proceeds. Basal progenitor cells of the olfactory epithelium transition into nascent OSNs marked by Cxcr4 expression and the initial extension of basal and apical neurites. Nascent OSNs become immature OSNs within 24-48 h. Immature OSN differentiation requires about a week and at least 2 stages. Early-stage immature OSNs initiate expression of genes encoding key transcriptional regulators and structural proteins necessary for further neuritogenesis. Late-stage immature OSNs begin expressing genes encoding proteins important for energy production and neuronal homeostasis that carry over into mature OSNs. The transition to maturity depends on massive expression of one allele of one odorant receptor gene, and this results in expression of the last 8% of genes expressed by mature OSNs. Many of these genes encode proteins necessary for mature function of axons and synapses or for completing the elaboration of non-motile cilia, which began extending from the newly formed dendritic knobs of immature OSNs. The cilia from adjoining OSNs form a meshwork in the olfactory mucus and are the site of olfactory transduction. Immature OSNs also have a primary cilium, but its role is unknown, unlike the critical role in proliferation and differentiation played by the primary cilium of the olfactory epithelium's horizontal basal cell.

Xenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites). Enzymes, such as cytochrome P450 and glutathione transferases (GSTs), have been proposed to participate in odorant clearance in insects and mammals as odorant metabolizing enzymes. This study aims to explore the function of GSTs in human olfaction. Using immunohistochemical methods, GSTs were found to be localized in human tissues surrounding the olfactory epithelium. Then, the activity of 2 members of the GST family toward odorants was measured using heterologously expressed enzymes. The interactions/reactions with odorants were further characterized using a combination of enzymatic techniques. Furthermore, the structure of the complex between human GSTA1 and the glutathione conjugate of an odorant was determined by X-ray crystallography. Our results strongly suggest the role of human GSTs in the modulation of odorant availability to ORs in the peripheral olfactory process.

Honeybees rely on nectar as their main source of carbohydrates. Sucrose, glucose, and fructose are the main components of plant nectars. Intriguingly, honeybees express only 3 putative sugar receptors (AmGr1, AmGr2, and AmGr3), which is in stark contrast to many other insects and vertebrates. The sugar receptors are only partially characterized. AmGr1 detects different sugars including sucrose and glucose. AmGr2 is assumed to act as a co-receptor only, while AmGr3 is assumedly a fructose receptor. We show that honeybee gustatory receptor AmGr3 is highly specialized for fructose perception when expressed in Xenopus oocytes. When we introduced nonsense mutations to the respective AmGr3 gene using CRISPR/Cas9 in eggs of female workers, the resulting mutants displayed almost a complete loss of responsiveness to fructose. In contrast, responses to sucrose were normal. Nonsense mutations introduced by CRISPR/Cas9 in honeybees can thus induce a measurable behavioral change and serve to characterize the function of taste receptors in vivo. CRISPR/Cas9 is an excellent novel tool for characterizing honeybee taste receptors in vivo. Biophysical receptor characterization in Xenopus oocytes and nonsense mutation of AmGr3 in honeybees unequivocally demonstrate that this receptor is highly specific for fructose.

A sweet taste receptor is composed of heterodimeric G-protein-coupled receptors T1R2 and T1R3. Although there are many sweet tastants, only a few compounds have been reported as negative allosteric modulators (NAMs), such as lactisole, its structural derivative 2,4-DP, and gymnemic acid. In this study, candidates for NAMs of the sweet taste receptor were explored, focusing on the structural motif of lactisole. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), has an α-methylacetic acid moiety, and this structure is also shared by lactisole and 2,4-DP. When ibuprofen was applied together with 1 mM aspartame to the cells that stably expressed the sweet taste receptor, it inhibited the receptor activity in a dose-dependent manner. The IC50 value of ibuprofen against the human sweet taste receptor was calculated as approximately 12 μM, and it was almost equal to that of 2,4-DP, which is known as the most potent NAM for the receptor to date. On the other hand, when the inhibitory activities of other profens were examined, naproxen also showed relatively potent NAM activity against the receptor. The results from both mutant analysis for the transmembrane domain (TMD) of T1R3 and docking simulation strongly suggest that ibuprofen and naproxen interact with T1R3-TMD, similar to lactisole and 2,4-DP. However, although 2,4-DP and ibuprofen had almost the same inhibitory activities, these activities were acquired by filling different spaces of the ligand pocket of T1R3-TMD; this knowledge could lead to the rational design of a novel NAM against the sweet taste receptor.

Visual and olfactory communications are vital for coordinated group hunting in most animals. To hunt for prey, the group-raiding termite specialist ant Megaponera analis, which lacks good vision, must first confirm the presence or absence of conspecific raiders. Here, we show that M. analis uses olfactory cues for intraspecific communication and showed greater preference for conspecific odors over clean air (blank) or odors from its termite prey. Chemical analysis of ant volatiles identified predominantly short-chained hydrocarbons. Electrophysiological analysis revealed differential sensory detection of the odor compounds, which were confirmed in behavioral olfactometric choice assays with odor bouquets collected from major and minor castes and the 2 most dominant volatiles and n-undecane n-tridecane. A comparative analysis of the cuticular hydrocarbon profile with those of the short-chained odor bouquet of different populations shows a high divergence in the long-chained profile and a much-conserved short-chained odor bouquet. This suggests that there is less selection pressure for divergence and individual recognition in the short- than the long-chained odor profiles. We conclude that olfactory communication serves as an alternative to visual or sound communication, especially during group raids in M. analis when ants are not in direct contact with one another.

Rostral forebrain structures, such as the central nucleus of the amygdala (CeA), send projections to the nucleus of the solitary tract (NST) and the parabrachial nucleus (PBN) that modulate taste-elicited responses. However, the proportion of forebrain-induced excitatory and inhibitory effects often differs when taste cell recording changes from the NST to the PBN. The present study investigated whether this descending influence might originate from a shared or distinct population of neurons marked by expression of somatostatin (Sst). In Sst-reporter mice, the retrograde tracers' cholera toxin subunit B AlexaFluor-488 and -647 conjugates were injected into the taste-responsive regions of the NST and the ipsilateral PBN. In Sst-cre mice, the cre-dependent retrograde tracers' enhanced yellow fluorescent protein Herpes Simplex Virus (HSV) and mCherry fluorescent protein HSV were injected into the NST and the ipsilateral PBN. The results showed that ~40% of CeA-to-PBN neurons expressed Sst compared with ~ 23% of CeA-to-NST neurons. For both the CeA Sst-positive and -negative populations, the vast majority projected to the NST or PBN but not both nuclei. Thus, a subset of CeA-to-NST and CeA-to-PBN neurons are marked by Sst expression and are largely distinct from one another. Separate populations of CeA/Sst neurons projecting to the NST and PBN suggest that differential modulation of taste processing might, in part, rely on differences in local brainstem/forebrain synaptic connections.

Sweet flavorants enhance palatability and intake of alcohol in adolescent humans. We asked whether sweet flavorants have similar effects in adolescent rats. The inherent flavor of ethanol in adolescent rats is thought to consist of an aversive odor, bitter/sweet taste, and burning sensation. In Experiment 1, we compared ingestive responses of adolescent rats to 10% ethanol solutions with or without added flavorants using brief-access lick tests. We used 4 flavorants, which contained mixtures of saccharin and sucrose or saccharin, sucrose, and maltodextrin. The rats approached (and initiated licking from) the flavored ethanol solutions more quickly than they did unflavored ethanol, indicating that the flavorants attenuated the aversive odor of ethanol. The rats also licked at higher rates for the flavored than unflavored ethanol solutions, indicating that the flavorants increased the naso-oral acceptability of ethanol. In Experiment 2, we offered rats chow, water, and a flavored or unflavored ethanol solution every other day for 8 days. The rats consistently consumed substantially more of the flavored ethanol solutions than unflavored ethanol across the 8 days. When we switched the rats from the flavored to unflavored ethanol for 3 days, daily intake of ethanol plummeted. We conclude that sweet and sweet/maltodextrin flavorants promote high daily intake of ethanol in adolescent rats (i.e., 6-10 g/kg) and that they do so in large part by improving the naso-oral sensory attributes of ethanol.

Under natural conditions, an animal orienting to an air-borne odor plume must contend with the shifting influence of meteorological variables, such as air temperature, humidity, and wind speed, on the location and the detectability of the plume. Despite their importance, the natural statistics of such variables are difficult to reproduce in the laboratory and hence few studies have investigated strategies of olfactory orientation by mobile animals under different meteorological conditions. Using trained search and rescue dogs, we quantified the olfactory orientation behaviors of dogs searching for a trail (aged 1-3 h) of a hidden human subject in a natural landscape, under a range of meteorological conditions. Dogs were highly successful in locating the human target hidden 800 m from the start location (93% success). Humidity and air temperature had a significant effect on search strategy: as air conditions became cooler and more humid, dogs searched significantly closer to the experimental trail. Dogs also modified their speed and head position according to their search location distance from the experimental trail. When close to the trail, dogs searched with their head up and ran quickly but when their search took them farther from the trail, they were more likely to search with their nose to the ground, moving more slowly. This study of a mammalian species responding to localized shifts in ambient conditions lays the foundation for future studies of olfactory orientation, and the development of a highly tractable mammalian species for such research.