High concentrations of dietary salt are harmful to health. Like most animals, Drosophila melanogaster are attracted to foods that have low concentrations of salt, but show strong taste avoidance of high salt foods. Salt in known on multiple classes of taste neurons, activating Gr64f sweet-sensing neurons that drive food acceptance and 2 others (Gr66a bitter and Ppk23 high salt) that drive food rejection. Here we find that NaCl elicits a bimodal dose-dependent response in Gr64f taste neurons, which show high activity with low salt and depressed activity with high salt. High salt also inhibits the sugar response of Gr64f neurons, and this action is independent of the neuron's taste response to salt. Consistent with the electrophysiological analysis, feeding suppression in the presence of salt correlates with inhibition of Gr64f neuron activity, and remains if high salt taste neurons are genetically silenced. Other salts such as Na2SO4, KCl, MgSO4, CaCl2, and FeCl3 act on sugar response and feeding behavior in the same way. A comparison of the effects of various salts suggests that inhibition is dictated by the cationic moiety rather than the anionic component of the salt. Notably, high salt-dependent inhibition is not observed in Gr66a neurons-response to a canonical bitter tastant, denatonium, is not altered by high salt. Overall, this study characterizes a mechanism in appetitive Gr64f neurons that can deter ingestion of potentially harmful salts.
Early research has shown variations in salt taste qualities in depression, anxiety, and stress. These studies evaluated changes to salt taste intensity and liking (pleasantness) of salt solutions but not of salty foods. Therefore, an Australian population survey (n = 424) was conducted where participants rated recalled intensity and liking of salt index foods and completed the Depression, Anxiety, and Stress Scale (DASS-21) to measure these states. Standard least squares regression (post hoc Tukey's HSD) compared means between groups, and nominal logistic regression assessed differences in distributions between categories. Higher salt liking was found in participants with DASS-21 scores indicative of severe depression (68.3 vs. 60.0, P = 0.005) and severe anxiety (68.4 vs. 60.0, P = 0.001) in comparison to those with normal scores, in all models. Higher salt liking was found in participants with DASS-21 scores indicative of moderate stress (67.7 vs. 60.2, P = 0.009) in the unadjusted model only. Higher salt liking was found in females with DASS-21 scores indicative of anxiety and stress, and in males with indicative depression and anxiety. No relationships between salt taste intensity ratings and the mood states were found. Results indicate that liking salty foods is positively correlated with depression, anxiety, and stress scores. Further research on the relationships between salt liking and intake of salt and salty foods, and the biological mechanisms of these mood states are needed to direct the application of findings toward potential new risk assessment measures, dietary interventions, or therapeutics.
Abundant evidence indicates that humans can communicate threat-related information to conspecifics through their body odors. However, prior research has been primarily conducted on Western (WEIRD) samples. In this study, we aimed to investigate whether threat-related information can be transmitted by individuals of East Asian descent who carry a single-nucleotide polymorphism (SNP) 538G -> A in the ABCC11 gene, which significantly reduces (noticeable) body odor. To examine this, we recruited 18 self-identified male East Asian AA-homozygotes and 18 self-identified male Western individuals who were carriers of the functional G-allele. We collected samples of their fear-related and neutral body odors. Subsequently, we conducted a double-blind behavioral experiment in which we presented these samples to 69 self-identified female participants of Western Caucasian and East Asian backgrounds. The participants were asked to rate faces that were morphed between expressions of fear and disgust. Notably, despite the "odorless" phenotypical expression of the ABCC11-mutation in East Asians, their fear odor caused a perceptual fear bias in both East Asian and Caucasian receivers. This finding leaves open the possibility of universal fear chemosignaling. Additionally, we conducted exploratory chemical analysis to gain initial insights into the chemical composition of the body odors presented. In a subsequent pre-registered behavioral study (N = 33), we found that exposure to hexadecanoic acid, an abundant compound in the fear and neutral body odor samples, was sufficient to reproduce the observed behavioral effects. While exploratory, these findings provide insight into how specific chemical components can drive chemical fear communication.
The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by their specific measurement of neural processes, have strongly contributed to this evidence. There is still no consensus as to whether such a bias exists in the chemical senses; chemosensory event-related potentials (CSERP) are an excellent tool to clarify the heterogeneous results, especially since the Late Positive Component (LPC) may be an indicator of emotional involvement after chemosensory stimulation. This research examined the association between state and trait anxiety and the amplitude and latency of pure olfactory and mixed olfactory-trigeminal LPC. In this study, 20 healthy participants (11 women) with a mean age of 24.6 years (SD=2.6) completed a validated questionnaire to measure anxiety (STAI), and CSERP were recorded during 40 pure olfactory stimulations (phenyl ethanol) and 40 mixed olfactory-trigeminal stimulations (eucalyptol). LPC latency and amplitude were measured at Cz for each participant. We observed a significant negative correlation between LPC latencies and the state anxiety scores for the mixed olfactory-trigeminal condition (r(18) = -.513; p = .021), but not for the pure olfactory condition. We did not observe any effect on LPC amplitudes. This study suggests that a higher level of state anxiety is related to a more rapid perceptual electrophysiological response for mixed olfactory-trigeminal stimuli but not for pure odors.
The underlying mechanisms of taste interactions in humans are not well understood, and three mechanisms have been proposed, namely a chemical interaction, a peripheral physiological, and a central mechanism. In the present study, it was investigated which of these mechanisms causes the suppression of sweetness by citric acid. This was investigated using a split-tongue gustometer that can stimulate the two sides of the tongue with different stimuli simultaneously, enabling a comparison of sucrose and citric acid presented either separately on each side of the tongue simultaneously or in a mixture on one side. Two studies were conducted using low (Study 1; n = 50) and high (Study 2: n = 59) concentrations of sucrose (2.5% (w/w) and 10% (w/w), respectively), and citric acid (0.14% (w/w) and 0.18% (w/w), respectively). In neither of the studies was there a significant difference in sweetness intensity ratings between the two conditions where sucrose and citric acid were presented either separately or in a mixture form. However, both showed significantly lower sweetness ratings than without citric acid indicating suppression of the sweetness of sucrose from citric acid. This provides strong evidence for a central mechanism for the suppression of the sweetness of sucrose by citric acid. This mechanism seems to be equal in high and low concentrations of both sucrose and citric acid.
People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with 10 household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 5,225 self-reported a respiratory illness and were grouped based on their reported COVID test results: COVID-positive (COVID+, N = 3,356), COVID-negative (COVID-, N = 602), and COVID unknown for those waiting for a test result (COVID?, N = 1,267). The participants who reported no respiratory illness were grouped by symptoms: sudden smell/taste changes (STC, N = 4,445), other symptoms excluding smell or taste changes (OthS, N = 832), and no symptoms (NoS, N = 416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% confidence interval (CI): 15-28%), 47% in smell (95% CI: 37-56%), and 17% in oral irritation (95% CI: 10-25%) intensity. There were medium to strong correlations between perceived intensities and self-reported abilities (r = 0.84 for smell, r = 0.68 for taste, and r = 0.37 for oral irritation). Our study demonstrates that COVID-19-positive individuals report taste dysfunction when self-tested with stimuli that have little to none olfactory components. Assessing the smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and may help to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.
Journal Article The psychophysical assessment of gustatory dysfunction in COVID-19 Get access Constantin A Hintschich, Constantin A Hintschich Department of Otorhinolaryngology, Regensburg University Hospital, Regensburg, Germany Corresponding author: Department of Otorhinolaryngology, Regensburg University Hospital, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Email: constantin.hintschich@klinik.uni-regensburg.de https://orcid.org/0000-0002-5500-600X Search for other works by this author on: Oxford Academic PubMed Google Scholar David T Liu, David T Liu Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria https://orcid.org/0000-0001-6948-737X Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Hummel Thomas Hummel Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany https://orcid.org/0000-0001-9713-0183 Search for other works by this author on: Oxford Academic PubMed Google Scholar Chemical Senses, Volume 48, 2023, bjad011, https://doi.org/10.1093/chemse/bjad011 Published: 21 June 2023 Article history Editorial decision: 28 March 2023 Corrected and typeset: 21 June 2023 Published: 21 June 2023
Sniffing is a commonly displayed behavior in rodents, yet how this important behavior adjusts throughout development to meet the sensory demands of the animals has remained largely unexplored. In this issue of Chemical Senses, Boulanger-Bertolus et al. investigates the ontogeny of odor-evoked sniffing through a longitudinal study of rats engaged in several olfactory paradigms from infancy to adulthood. The results of this study yield a cohesive picture of sniffing behavior across three developmental stages, while also providing direct comparisons within subjects between these timepoints. As we discuss herein, these results advance the field in relation to existing literature on the development of odor-evoked sniffing behavior in several important ways.
Animals use sour taste to avoid spoiled food and to choose foods containing vitamins and minerals. To investigate the response to sour taste substances during vitamin C (ascorbic acid; AA) deficiency, we conducted behavioral, neural, anatomical, and molecular biological experiments with osteogenic disorder Shionogi/Shi Jcl-od/od rats, which lack the ability to synthesize AA. Rats had higher 3 mM citric acid and 10 mM AA preference scores when AA-deficient than when replete. Licking rates for sour taste solutions [AA, citric acid, acetic acid, tartaric acid, and HCl] were significantly increased during AA deficiency relative to pre- and postdeficiency. Chorda tympani nerve recordings were conducted to evaluate organic acid taste responses in the AA-deficient and replete rats. Nerve responses to citric acid, acetic acid, and tartaric acid were significantly diminished in AA-deficient rats relative to replete controls. There was no significant difference in the number of fungiform papillae taste buds per unit area in the AA-deficient rats relative to the replete rats. However, mRNA expression levels of Gnat3 (NM_173139.1), Trpm5 (NM_001191896.1), Tas1r1 (NM_053305.1), Car4 (NM_019174.3), and Gad1 (NM_017007.1) in fungiform papillae taste bud cells from AA-deficient rats were significantly lower than those in replete rats. Our data suggest that AA deficiency decreases avoidance of acids and reduces chorda tympani nerve responses to acids. AA deficiency downregulates some taste-related genes in fungiform papillae taste bud cells. However, the results also reveal that the mRNA expression of some putative sour taste receptors in fungiform papillae taste bud cells is not affected by AA deficiency.
Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.
Oral temperature is a sensory cue relevant to food preference and nutrition. To understand how orally-sourced thermal inputs are represented in the gustatory cortex (GC) we recorded neural responses from the GC of male and female mice presented with deionized water at different innocuous temperatures (14 °C, 25 °C, 36 °C) and taste stimuli (room temperature). Our results demonstrate that GC neurons encode orally-sourced thermal information in the absence of classical taste qualities at the single neuron and population levels, as confirmed through additional experiments comparing GC neuron responses to water and artificial saliva. Analysis of thermal-evoked responses showed broadly tuned neurons that responded to temperature in a mostly monotonic manner. Spatial location may play a minor role regarding thermosensory activity; aside from the most ventral GC, neurons reliably responded to and encoded thermal information across the dorso-ventral and antero-postero cortical axes. Additional analysis revealed that more than half of GC neurons that encoded chemosensory taste stimuli also accurately discriminated thermal information, providing additional evidence of the GC's involvement in processing thermosensory information important for ingestive behaviors. In terms of convergence, we found that GC neurons encoding information about both taste and temperature were broadly tuned and carried more information than taste-selective only neurons; both groups encoded similar information about the palatability of stimuli. Altogether, our data reveal new details of the cortical code for the mammalian intraoral thermosensory system in behaving mice and pave the way for future investigations on GC functions and operational principles with respect to thermogustation.
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 5x 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 degrees C to 30 degrees 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).
A growing body of research suggests that emotional chemosignals in others' body odor (BO), particularly those sampled during fearful states, enhance emotional face perception in conscious and preconscious stages. For instance, emotional faces access visual awareness faster when presented with others' fear BOs. However, the effect of these emotional signals in self-BO, that is, one's own BO, is still neglected in the literature. In the present work, we sought to determine whether emotional self-BOs modify the access to visual awareness of emotional faces. Thirty-eight women underwent a breaking-Continuous Flash Suppression task in which they were asked to detect fearful, happy, and neutral faces, as quickly and accurately as possible, while being exposed to their fear, happiness, and neutral self-BOs. Self-BOs were previously collected and later delivered via an olfactometer, using an event-related design. Results showed a main effect of emotional faces, with happy faces being detected significantly faster than fearful and neutral faces. However, our hypothesis that fear self-BOs would lead to faster emotional face detection was not confirmed, as no effect of emotional self-BOs was found-this was confirmed with Bayesian analysis. Although caution is warranted when interpreting these results, our findings suggest that emotional face perception is not modulated by emotional self-BOs, contrasting with the literature on others' BOs. Further research is needed to understand the role of self-BOs in visual processing and emotion perception.
Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.
Odors guide food seeking, and food intake modulates olfactory function. This interaction is mediated by appetite-regulating hormones like ghrelin, insulin, and leptin, which alter activity in the rodent olfactory bulb, but their effects on downstream olfactory cortices have not yet been established in humans. The olfactory tract connects the olfactory bulb to the cortex through 3 main striae, terminating in the piriform cortex (PirC), amygdala (AMY), olfactory tubercule (OT), and anterior olfactory nucleus (AON). Here, we test the hypothesis that appetite-regulating hormones modulate olfactory processing in the endpoints of the olfactory tract and the hypothalamus. We collected odor-evoked functional magnetic resonance imaging (fMRI) responses and plasma levels of ghrelin, insulin, and leptin from human subjects (n = 25) after a standardized meal. We found that a hormonal composite measure, capturing variance relating positively to insulin and negatively to ghrelin, correlated inversely with odor intensity ratings and fMRI responses to odorized vs. clean air in the hypothalamus, OT, and AON. No significant correlations were found with activity in PirC or AMY, the endpoints of the lateral stria. Exploratory whole-brain analyses revealed significant correlations near the diagonal band of Broca and parahippocampal gyrus. These results demonstrate that high (low) blood plasma concentrations of insulin (ghrelin) decrease perceived odor intensity and odor-evoked activity in the cortical targets of the medial and intermediate striae of the olfactory tract, as well as the hypothalamus. These findings expand our understanding of the cortical mechanisms by which metabolic hormones in humans modulate olfactory processing after a meal.
Olfactory tests are used for the evaluation of ability to detect and identify common odors in humans psychophysically. Olfactory tests are currently administered by professionals with a set of given odorants. Manual administration of such tests can be labor and cost intensive and data collected as such are confounded with experimental variables, which adds personnel costs and introduces potential errors and data variability. For large-scale and longitudinal studies, manually recorded data must be collected and compiled from multiple sites. It is difficult to standardize the way data are collected and recorded. There is a need for a computerized smell test system for psychophysical and clinical applications. A mobile digital olfactory testing system (DOTS) was developed, consisting of an odor delivery system (DOTS-ODD) and a mobile application program (DOTS-APP) connected wirelessly. The University of Pennsylvania Smell Identification Test was implemented in DOTS and compared to its commercial product on a cohort of 80 normosmic subjects and a clinical cohort of 12 Parkinson's disease patients. A test-retest was conducted on 29 subjects of the normal cohort. The smell identification scores obtained from the DOTS and standard UPSIT commercial test are highly correlated (r = 0.714, P < 0.001), and test-retest reliability coefficient was 0.807 (r = 0.807, P < 0.001). The DOTS is customizable and mobile compatible, which allows for the implementation of standardized olfactory tests and the customization of investigators' experimental paradigms. The DOTS-APP on mobile devices offers capabilities for a broad range of on-site, online, or remote clinical and scientific chemosensory applications.
Smell detection depends on nasal airflow, which can make absorption of odors to the olfactory epithelium by diffusion through the mucus layer. The odors then act on the chemo-sensitive epithelium of olfactory sensory neurons (OSNs). Therefore, any pathological changes in the olfactory area, for instance, dry nose caused by Sjögren’s Syndrome (SS) may interfere with olfactory function. SS is an autoimmune disease in which aquaporin (AQP) 5 autoantibodies have been detected in the serum. However, the expression of AQP5 in olfactory mucosa and its function in olfaction is still unknown. Based on the study of the expression characteristics of AQP5 protein in the nasal mucosa, the olfaction dysfunction in AQP5 knockout (KO) mice was found by olfactory behavior analysis, which was accompanied by reduced secretion volume of Bowman’s gland by using in vitro secretion measure system, and the change of acid mucin in nasal mucus layer was identified. By excluding the possibility that olfactory disturbance was caused by changes in OSNs, the result indicated that AQP5 contributes to olfactory functions by regulating the volume and composition of OE mucus layer, which is the medium for the dissolution of odor molecules. Our results indicate that AQP5 can affect the olfactory functions by regulating the water supply of BGs and the mucus layer upper the OE that can explain the olfactory loss in the patients of SS, and AQP5 KO mice might be used as an ideal model to study the olfactory dysfunction.
Olfactory and declarative memory performances are associated, as both functions are processed by overlapping medial-temporal and prefrontal structures and decline in older adults. While a decline in olfactory identification may be related to a decline in declarative memory, the relationship between olfactory detection threshold and declarative memory remains unclear. In this meta-analysis, we assessed (i) the relationship between olfactory identification/detection threshold and verbal declarative memory in cognitively normal older adults, and (ii) the effect of age on these relationships. We included articles from PsychNet, PubMed, and Academic Search Complete according to the following criteria: (i) inclusion of cognitively normal older adults; (ii) assessment of episodic or semantic memory; and (iii) assessment of olfactory identification or detection threshold. Seventeen studies and 22 effect sizes were eligible and included in this meta-analysis. Olfactory identification was associated with episodic (small effect size: r = 0.19; k = 22) and semantic memory (small effect size: r = 0.16; k = 23). Similarly, the olfactory detection threshold was associated with both episodic (small to medium effect size: r = 0.25; k = 5) and semantic memory (small effect size: r = 0.17; k = 7). Age was found to moderate the relationship between olfactory detection threshold and memory performance. Both olfactory identification and detection threshold performances are associated with declarative memory in older adults, and age only moderates the relationship between olfactory detection threshold and declarative memory performances.
Olfactory training (OT) has been shown to be of value in the treatment of olfactory dysfunction. The present study aimed to investigate whether the efficacy of OT could be modulated with multisensory integration, attention towards odors, odor complexity, or physical activity assessed with a questionnaire. One hundred healthy participants were recruited and divided into 4 groups. Except for controls (n = 26, mean age +/- SD = 36 +/- 15 years) all participants performed OT 4 times a day. In the "video" group (n = 26, age 39 +/- 19 years) OT was performed while watching specific and congruent video sequences. In the "counter" group (n = 24, 38 +/- 17 years) participants additionally counted the number of odors 1 day per week, and in the "training only" group no additional measures were taken in addition to OT (n = 24, 38 +/- 20 years). "Single-molecule" odorants or "complex mixtures" were distributed randomly for training stimulation. Sniffin' sticks tests (odor identification, odor discrimination, and odor threshold), cognitive tests, and a series of scales were measured at both baseline and after 3 months of OT. The degree of physical activity was recorded with a questionnaire. Olfactory function improved in the video and counter groups after OT, especially for odor threshold and discrimination. Yet, odor complexity and the degree of physical activity had limited effects on olfactory improvement after OT. Both multisensory interaction and attention towards odors plus OT appeared to facilitate improvement of olfactory function in healthy individuals compared with OT alone and controls, which could provide new promising treatments for clinical applications.
