In line with the critical role of human olfaction in motivated behavior, positively valenced odors have been shown to boost hedonic perception of visual stimuli, especially facial expressions, compared to unpleasant smells. However, it remains unclear whether pleasant fragrances, which vary in character and subjective affective profile, differentially impact different categories of visual stimuli. We also postulate that individual differences in emotional responses to odors modulate their subsequent effect on hedonic evaluations of images. The current study investigated how (relative to a clean air control) 4 pleasant odors (vanilla, rose, lavender, and lemon) influenced hedonic ratings of different categories of visual images (faces, landscapes, and objects), with each category comprising images of neutral and positive valence. Forty participants (aged 18 to 35) rated the pleasantness of each image during each odor condition presented using a computer-controlled olfactometer. Participants also reported their emotional response to each fragrance on 7 dimensions (happiness, disgust, relaxation, thirstiness, sensuality, energy, and nostalgia) using the Liverpool Emotion and Odor Scale (LEOS), self-report questionnaire. Pleasant odors significantly affected image pleasantness ratings, but the effects of specific fragrances differed by image category. Individual differences in emotional experiences elicited by each fragrance were shown to modulate the impact of odors on hedonic evaluations, and these effects varies across the different image categories. The findings offer new insights into the differential effects of pleasant odors on hedonic evaluations of visual stimuli and the role of individual affective processing in cross-modal olfactory-visual integration.

Animals use their sense of smell for survival and well-being. Any disruption to olfactory perception, can lead to devastating consequences and decreased quality of life. Psychedelics alter perception in humans, yet little is known about the impact of psychedelics on olfactory behaviors. Using an olfactory search task, we investigated the impact of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on olfactory search behavior of mice. We found that DOI decreases search accuracy, alters movement, and increases sniff rate. These findings suggest that DOI disrupts olfactory-guided behavior, elucidating psychedelic-induced changes to olfactory processes.

Taste modulation induced by interactions among specific compounds remains poorly understood. L-histidine and creatinine are both bitter compounds abundant in dried bonito dashi. This study investigated whether 10 bitter compounds could shift the taste quality of L-histidine from bitterness toward sweetness, as assessed by sensory evaluation using a fixed-sum method. When presented alone, 4% L-histidine elicited bitterness accompanied by weak sweetness, whereas iso-bitter creatinine evoked predominantly bitterness. Remarkably, pre-stimulation with creatinine shifted the taste quality of L-histidine toward sweetness. Similar effects were observed after pre-stimulation with isoleucine, tryptophan, phenylalanine, and creatine, but not with histidine, valine, leucine, caffeine, or carnosine. This effect was transient, as increasing the interval after creatinine pre-stimulation restored the bitterness of L-histidine. In addition, 0.1% NaCl altered the bitterness-to-sweetness balance of L-histidine toward sweetness after pre-stimulation with creatinine. The taste quality of histidine alone was highly sensitive to pH: bitterness peaked at pH 7.0, whereas sweetness increased under alkaline conditions. In contrast, varying the pH of the pre-stimulation solution between 5.0 and 8.0 did not affect the modulation of L-histidine taste. These findings demonstrate a previously unrecognized histidine-specific form of taste modulation, suggesting interactions among naturally coexisting bitter compounds may dynamically alter taste qualities in traditional broths and other complex foods.

Sodium ascorbate (AsA-Na) is widely used as a source of vitamin C. However, the mechanisms regulating voluntary intake across different concentrations and nutritional states remain poorly understood. Therefore, we examined behavioral and neural responses to AsA-Na in osteogenic disorder Shionogi (ODS) od/od rats, which lack endogenous vitamin C synthesis. Two-bottle choice tests were used to evaluate long-term behavioral responses, and the contribution of epithelial sodium channel (ENaC)-dependent taste signaling was examined using amiloride. In parallel, chorda tympani (CT) nerve responses were recorded with and without amiloride treatment. AsA-Na consistently showed lower preference scores than NaCl across concentrations. At 30 to 100 mM, the preference for AsA-Na was lower than that for NaCl but significantly higher than that for AsA. Lick responses to AsA-Na were comparable to those for NaCl and were enhanced under vitamin C-deficient conditions. Although the 48-h intake of 100 mM AsA-Na remained low under all conditions, the intake of 10 mM AsA-Na increased selectively during the re-intake phase. Notably, amiloride strongly suppressed CT nerve responses to AsA-Na. While amiloride significantly reduced NaCl preference and intake, it had no effect on AsA-Na preference or sustained intake. These results support a dissociation between ENaC-mediated peripheral sensory signaling and long-term ingestive behavior. Although AsA-Na is detected via sodium taste pathways, this sensory input alone cannot account for sustained intake. Instead, intake is likely influenced by post-ingestive mechanisms in a concentration- and state-dependent manner. These findings suggest an important contribution of internal nutritional signals in shaping chemosensory-driven behavior.

Precise control of odorant concentration is essential for reliable olfactory research, yet existing odorant delivery methods often suffer from solvent interactions and dilution from ambient air, limiting stimulus consistency in olfactory research. We developed an odor sampling bag system using Nalophan plastic to create a closed headspace with air as the carrier medium, eliminating solvent-related variability and ambient air dilution. In 2 independent experiments, 15 participants each rated the perceived intensity of 7 concentrations of benzaldehyde and 2-heptanone using both gas-sampling bags and glass jars. Bags produced higher maximum perceptual intensities (P < 0.001) and greater test-retest reliability than jars (experiment 1: r = 0.89 vs. 0.81, P < 0.001; experiment 2: r = 0.86 vs. 0.72, P < 0.001). Notably, the 2 tested odorants showed different maximum intensities in bags (P < 0.001) but not jars (P = 0.85), suggesting bags better preserve odorant-specific concentration differences. Photoionization detector measurements confirmed stable headspace concentrations over time, comparable to industry-standard Tedlar bags. This affordable, easy-to-implement method accurately delivers desired odor concentrations without requiring expensive olfactometry equipment, offering a practical solution for olfactory psychophysics research.

Resident stem cells support tissue maintenance in self-renewing adult tissue niches, including the olfactory epithelium, the peripheral organ for smell. In adult mammals, olfactory basal cells support neurogenesis and barrier epithelial maintenance, but whether additional stem cell compartments contribute to olfactory epithelial reconstitution remains unclear. Using lineage tracing, culture models, and single-cell RNA sequencing (scRNA-seq), we demonstrate directly that cells within adult murine submucosal Bowman's glands give rise to olfactory epithelial sustentacular cells, only after severe epithelial lesion. Modeling scRNA-seq data identifies BMP family ligands, expressed by basal stem cells, as potential signals modulating Bowman's gland differentiation. We developed a Bowman's gland culture model, providing an in vitro platform for testing differentiation. Informed by scRNA-seq modeling, treatment of cultures with BMP7/GDF5/GDF11 drove sustentacular cell differentiation. Together, these findings identify Bowman's glands as an injury-responsive facultative stem cell population capable of contributing to olfactory epithelial repair, a process necessary for maintenance of olfactory function.

Processing of contaminants in odor mixtures is influenced by their categorization into food and nonfood categories. For example, we previously found that participants were more likely to perceive food odors as contaminated by nonfood odors than vice versa, and that this effect was robust to changes in explicit task instructions. However, due to the mixing of food and nonfood components, processing differences between categories were not captured by this task design and thus remain to be explored. In the current pre-registered study, we address this knowledge gap by determining the effects of attention on the perception of odor mixtures containing only food or nonfood components. Participants (N = 24) assessed the perceived dominance of a target odor within an odor mixture. Response times to all odors increased toward the dilution series' midpoint and were faster for food odor compared to nonfood odor mixtures. Perceived target dominance increased linearly for nonfood targets but exhibited a sigmoidal shape with a steeper slope (smaller just-noticeable difference) for food targets. This implies that distinguishing 2 food odors was easier than distinguishing between 2 nonfood odors, likely due to definitions higher relevance of distinct object category boundaries subserving contamination avoidance. At the same time, contamination sensitivity might be lower for nonfoods, allowing for greater tolerance of deviations. Attention did not influence the perception of nonfood but did so for ambivalent food mixtures and when the target was completely absent.

One of the key challenges to predict odor from the molecular structure is unarguably our limited understanding of the odor space and the complexity of the underlying structure-odor relationships. Here, we introduce an expert-curated taxonomy (ET) that captures the hierarchical relations between odor descriptors for molecular datasets. To quantify the usefulness and relevance of this expert taxonomy, we provide a systematic validation that leverages the predictive performance of machine learning models for structure-based odor predictions, as well as known structure-odor relationships. As a control next to the ET based on semantic and perceptual similarities, we provide a data-driven taxonomy (DT) based on clustering co-occurrence patterns of odor descriptors from our expert-curated molecular dataset. The latter is derived from available datasets in the Pyrfume repository. Both taxonomies (ET and DT) add value in the semantic organization of odor descriptors and provide an avenue for novel insights in molecular structure-odor prediction. Together with in-depth validation steps that highlight the value of odor taxonomies, the quality of the ET is quantitatively assessed. The DT further allows critical evaluation of the expert taxonomy, identification of potential inconsistencies, and a better understanding of the molecular odor space. Finally, we highlight the results of the expert-curated taxonomy by showcasing odor predictions for the case of pear odorants used in perfumery. Both taxonomies as well as a full molecular dataset are made available to the community, providing a stepping stone for a future community-driven exploration of the molecular basis of smell.

The insular cortex plays a pivotal role in processing gustatory information. Compared to those of glutamatergic neurons, the activities of GABAergic neurons in the insular cortex during feeding behaviors are less well understood. If the insular cortex GABAergic neurons have same role as other sensory cortices, they will suppress redundant neuronal activities. To elucidate GABAergic neuronal activities and their correlation with glutamatergic neuronal activity during feeding behaviors, we recorded extracellular unit activities in the rat insular cortex during a cue-guided lever manipulation task in which saccharin solution was provided as a reward. Neurons were classified into fast-spiking-like and non-fast-spiking-like neurons using spike waveforms and firing rates. Compared with non-fast-spiking-like neurons, a larger population of fast-spiking-like neurons changed their firing rates during the task. When firing increases in fast-spiking-like neurons were observed, 45% to 50% of simultaneously recorded non-fast-spiking-like neurons showed increased firing rates. In contrast, during decreases in the firing rates of fast-spiking-like neurons, only 10% to 31% of simultaneously recorded non-fast-spiking-like neurons exhibited decreased firing rates. Cross-correlation analysis between fast-spiking-like and non-fast-spiking-like neurons revealed that the pairs showing changes in the firing rate in the same direction tended to exhibit greater synchronized activity than those showing distinct firing rate changes. These results suggest that GABAergic fast-spiking-like and glutamatergic neurons in the insular cortex discretely fire depending on the processing of taste information. These distinct activities may contribute not only to taste detection but also to preceding information processing, such as expectation and anticipation of the taste.

Approach and avoidance behavior towards sensory stimuli serve as powerful behavioral readouts of our mental representations of the external world and our expectations and motivations in navigating it. In the olfactory system, approach or avoidance of odors statistically associated with people, places, and things relate to ecologically critical functions like feeding, fear, and reproduction. However, experimental methods for quantifying approach/avoidance behavior in relative terms across odors have been limited. Here we present a novel method for quantifying mouse approach/avoidance in an open field arena scented with up to four odors simultaneously. In lieu of traditional inferential statistics (which greatly limit the information that can be learned in this multivariate experiment), we demonstrate the a priori definition of quantitative hypotheses for the distribution of time among scented corners and the use of information theory-derived statistical metrics to quantify the relative likelihood of each competing hypothesis given the data collected. Finally, we use data from a fear conditioning experiment to demonstrate the application of this method to conclude that fear conditioned mice exhibit a fear generalization gradient that decreases as odorants become more different from the threat-predictive odorant, as opposed to competing hypotheses that mice are specifically avoiding the threat-predictive odorant or have overgeneralized their fear and avoid all test odors regardless of similarity. Critically, this method takes only a few minutes per animal with no prior behavioral training required, and it can be performed easily without automated apparatus.

The accessory olfactory system is specialized for detecting chemical cues that elicit innate reproductive, social, and defensive behaviors and physiological responses in mammals. In mice, vomeronasal sensory neurons express three receptor families, type 1 vomeronasal receptors, type 2 vomeronasal receptors, and vomeronasal formyl peptide receptors, that collectively detect diverse semiochemicals, including pheromones, microbe-derived peptides, and predator cues. Recent advances in molecular organization, structural diversity, and ligand specificity have begun to clarify how vomeronasal receptor families encode ethologically relevant chemical signals, thereby providing initial insight into organizational principles of vomeronasal signaling, including labeled-line and integrative coding strategies. Nevertheless, the vast majority of vomeronasal receptors remain functionally uncharacterized, and the molecular logic of sensory coding in this system is still only partially understood. This review synthesizes current knowledge of vomeronasal receptor diversity, ligand recognition, and accessory mechanisms, while highlighting both the progress made and the major gaps that remain in understanding how receptor-derived signals are transformed into adaptive behavioral and physiological responses.

Many animals utilize pheromones as chemical substances that regulate reproductive and social behaviors. Elucidating how diverse pheromonal compounds are detected and translated into specific behavioral and physiological responses is crucial for understanding animal behavior. In vertebrates, pheromone reception is primarily mediated by the vomeronasal organ. Vomeronasal sensory neurons detect a broad range of semiochemical molecules, including pheromones and allelochemicals, and transmit this information via the accessory olfactory bulb to higher brain regions, such as the amygdala and hypothalamic regions. Although recent studies have advanced the identification of pheromonal molecules and the analysis of the neural circuits responsible for their detection, ligands have been identified for only a small fraction of the hundreds of vomeronasal receptors. Analyses of genetically engineered mice lacking key components of vomeronasal signal transduction in vomeronasal sensory neurons have provided comprehensive insights into the relationship between vomeronasal sensory input and behavioral output. This review focuses on pheromones among the semiochemicals detected by the vomeronasal organ and summarizes current understanding of pheromonal perception and associated social behaviors, primarily based on studies in mice, the most extensively investigated model organism to date.

Reliable and standardized assessment of human taste function remains a critical need in clinical and research settings. Here, we pooled individual participants' data of gustatory recognition thresholds from 6 studies (N > 500) that employed a unified methodology combining taste sprays with an adaptive Bayesian algorithm (QUEST) across 4 basic tastes: sweet, salty, sour, and bitter. Thresholds were estimated using a yes-no task format and psychometrically controlled stimuli, enabling efficient and precise estimation across individuals. Results revealed approximately normal distributions of thresholds within each modality, spanning 2 to 3 log units, and modest but consistent correlations between tastes. Gender and age influenced sensitivity, with women generally showing lower (better) thresholds than men, and older adults exhibiting reduced sensitivity, particularly for bitter and sweet tastes. A composite taste score derived from z-standardized thresholds showed stronger age- and gender-related effects than individual modalities, supporting its utility as a general index of taste function. These findings validate the use of the QUEST algorithm for gustatory psychophysics and provide preliminary normative data for taste sensitivity using time-efficient procedures. The consistency of results across studies supports the development of standardized protocols for clinical and population-level taste testing. Future research should extend this framework to broader populations and additional taste qualities to establish comprehensive benchmarks for gustatory health.

Taste cell regeneration and taste signaling are regulated by myriad growth factors and signaling molecules secreted by neurons and taste papillae-resident cells. The calcitonin-related polypeptide alpha (Calca) gene is a source of 4 biologically active peptides with varied physiological roles. Alternative splicing of the Calca messenger RNA generates either preprocalcitonin gene-related peptide (CGRP) or preprocalcitonin-encoding transcripts. Proteolytic processing of preprocalcitonin generates procalcitonin, calcitonin and katacalcin. Calcitonin is a ligand for the G protein coupled receptor calcitonin receptor (CALCR) while CGRP is a ligand for the CGRP receptor (CGRP1R) formed by the calcitonin receptor like receptor (CALCRL)-receptor activity modifying protein 1 (RAMP1) complex. Interestingly, procalcitonin too is a ligand for the CGRP1R where it can antagonize CGRP. CGRP expression in taste and trigeminal neurons has been documented and is posited to regulate taste signaling. Single cell and bulk RNASeq of taste papillae revealed that the preprocalcitonin but not the Cgrp transcript is expressed in Tas1r3-expressing type II taste cells, while CGRP1R subunits are expressed in taste stem/progenitor cells and by subsets of fibroblasts and immune cells in the lingual mesenchyme. We confirmed this expression pattern using quantitative polymerase chain reaction (qPCR) and histological techniques. qPCR of geniculate and nodose-petrosal-jugular ganglia revealed that both express Cgrp and CGRP1R subunit mRNAs, but not preprocalcitonin and Calcr. This interesting expression patterns suggests that procalcitonin and CGRP might reciprocally regulate the CGRP1R in the taste papillae and potentially influence taste signaling, taste cell regeneration, and the taste microbiome.

The purpose of the study was to develop a self-reporting measure of trigeminal function, addressing the need for the participants' self-perception of comfort and sensitivity related to trigeminal sensations. A 15-item questionnaire was designed and tested on the sample of n = 1,001 participants from the general population in Dresden, Germany, aged from 18 to 86. For validation included were ratings of nasal trigeminal stimuli using ammonium, lateralization of eucalyptol as a measure of trigeminal sensitivity, odor identification, and self-ratings of nasal airflow and olfactory function. Based on factor analyses, the initially intended structure of the questionnaire was revised to improve the tool's overall psychometric quality. Originally intended structure was not well supported. Exploratory factor analysis based on a scree plot indicated 1-factor solution, with the final version comprising 8 carefully selected items, providing the best fit. The questionnaire presented good reliability (Cronbach's α = 0.74) and satisfying validity, based on correlations with other self-reporting measures and group comparisons. Invariance analysis across gender suggested the use of separate norms for men and women. The trigeminal function questionnaire is a brief, reliable and valid measure for assessing self-perception of trigeminal function.