A review of the flavor profile of metal salts: understanding the complexity of metallic sensation

The oral sensation of metallic is a complex experience. Much of our current understanding of metallic sensation is from the investigation of metal salts, which elicit diverse sensations, including taste, smell, and chemesthetic sensations, and therefore meet the definition of a flavor rather than a taste. Due to the involvement of multiple chemosensory systems, it can be challenging to define and characterize metallic sensation. Here, we provide a comprehensive review of the psychophysical studies quantifying and characterizing metallic sensation, focusing on metal salts. We examine the factors that impact perception, including anion complex, concentration, nasal occlusion, and pH. In addition, we summarize the receptors thought to be involved in the perception of metallic sensation (i.e., TRPV1, T1R3, TRPA1, and T2R7) either as a result of in vitro assays or from studies in knock-out mice. By enhancing our scientific understanding of metallic sensation and its transduction pathways, it has the potential to improve food, pharmaceuticals, help identify suppression or masking strategies, and improve the ability to characterize individual differences in metallic sensation. It also has the potential to translate to clinical populations by addressing the disparities in knowledge and treatment options for individuals suffering from metallic taste disorder (i.e., phantom taste or “metal mouth”). Future psychophysical studies investigating the sensory perception of metal salts should include a range of compounds and diverse food matrices, coupled with modern sensory methods, which will help to provide a more comprehensive understanding of metallic sensation.

Automated quantification of vomeronasal glomeruli number, size, and color composition after immunofluorescent staining

Glomeruli are neuropil rich regions of the main or accessory olfactory bulbs where the axons of olfactory or vomeronasal neurons and dendrites of mitral/tufted cells form synaptic connections. In the main olfactory system olfactory sensory neurons (OSNs) expressing the same receptor innervate one or two glomeruli. However, in the accessory olfactory system, vomeronasal sensory neurons (VSNs) expressing the same receptor can innervate up to 30 different glomeruli in the accessory olfactory bulb (AOB). Genetic mutation disrupting genes with a role in defining the identity/diversity of olfactory and vomeronasal neurons can alter the number and size of glomeruli. Interestingly, two cell surface molecules, Kirrel2 and Kirrel3, have been indicated as playing a critical role in the organization of axons into glomeruli in the AOB. Being able to quantify differences in glomeruli features, such as number, size or immunoreactivity for specific markers, is an important experimental approach to validate the role of specific genes in controlling neuronal connectivity and circuit formation in either control or mutant animals. Since the manual recognition and quantification of glomeruli on digital images is a challenging and time-consuming task, we generated a program in Python able to identify glomeruli in digital images and quantify their properties, such as size, number, and pixel intensity. Validation of our program indicates that our script is a fast and suitable tool for high throughput quantification of glomerular features of mouse lines with different genetic makeup.

Predicting Olfactory Loss In Chronic Rhinosinusitis Using Machine Learning

Objective Compare machine learning (ML) based predictive analytics methods to traditional logistic regression in classification of olfactory dysfunction in chronic rhinosinusitis (CRS-OD), and identify predictors within a large multi-institutional cohort of refractory CRS patients. Methods Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study were assessed for baseline CRS-OD using a smell identification test (SIT) or brief SIT (bSIT). Four different ML methods were compared to traditional logistic regression for classification of CRS normosmics versus CRS-OD. Results Data were collected for 611 study participants who met inclusion criteria between April 2011 and July 2015. 34% of enrolled patients demonstrated olfactory loss on psychophysical testing. Differences between CRS normosmics and those with smell loss included objective disease measures (CT and endoscopy scores), age, sex, prior surgeries, socioeconomic status, steroid use, polyp presence, asthma, and aspirin sensitivity. Most ML methods performed favorably in terms of predictive ability. Top predictors include factors previously reported in the literature, as well as several socioeconomic factors. Conclusion Olfactory dysfunction is a variable phenomenon in CRS patients. ML methods perform well compared to traditional logistic regression in classification of normosmia versus smell loss in CRS, and are able to include numerous risk factors into prediction models. Several actionable features were identified as risk factors for CRS-OD. These results suggest that ML methods may be useful for current understanding and future study of hyposmia secondary to sinonasal disease, the most common cause of persistent olfactory loss in the general population.

Olfactory impairment and close social relationships. A narrative review

Olfactory impairment is one of the more unique symptoms of COVID-19 infection, and has therefore enjoyed increased public attention in recent months. Olfactory impairment has various implications and consequences ranging from difficulty detecting dangerous pathogens to hindering social functioning and social behaviours. We provide an overview of how olfactory impairment can impact three types of close social relationships; family relationships, friendships and romantic relationships. Evidence is divided into several categories representing potential mechanisms by which olfactory impairment can impact close social relationships: bonding disruptions, decreased social support, missed group-eating experiences, hygiene concerns, and altered sexual behaviours. We conclude with a discussion of emerging future research questions.

Perceptual Quality of Non-Esterified Fatty Acids Varies with Fatty Acid Chain Length

Non-esterified fatty acids (NEFA) are effective taste stimuli. The quality they impart has not been well characterized. Sourness, and “fattiness” have been reported, but an irritation component has also been described and how these transition with gradations of aliphatic chain length has not been systematically studied. This study examined intensity and quality ratings of NEFA's ranging from C2 to C18. Oral sites and the time course of sensations were also monitored. Given all NEFA contain carboxylic acid moieties capable of donating hydrogen ions, the primary stimulus for sour taste, testing was conducted with and without sour adaptation to explore the contribution of sour taste across the range of NEFA. Short chain NEFA (C2-C6) were rated as predominantly sour and this was diminished in C2 and C4 by sour adaptation. Medium chain NEFA (C8-C12) were rated as mainly irritating with long chain NEFA (C18) described mostly as bitter. The latter may reflect the lack of “fatty” lexicon to describe the sensation. Short chain NEFA were mostly localized to the anterior tongue and were of rapid onset. The sensation from medium chain NEFA was attributed to the lateral tongue while medium and long chain NEFA sensations were predominantly localized to the back of the tongue and throat and had a longer lag time. The findings indicate there is a systematic transition of NEFA taste quality and irritation with increments in chain length and this is consistent with multiple modes of transduction.

Parsing Sage and Rosemary in Time: The Machine Learning Race to Crack Olfactory Perception

Color and pitch perception are largely understandable from characteristics of a physical stimuli: the wavelengths of light and sound waves, respectively. By contrast, understanding olfactory percepts from odorous stimuli (volatile molecules) is much more challenging. No intuitive set of molecular features is up to the task. Here in Chemical Senses, the Ray lab reports using a predictive modeling framework--first breaking molecular structure into thousands of features and then using this to train a predictive statistical model on a wide range of perceptual descriptors--to create a tool for predicting the odor character of hundreds of thousands of available but previously uncharacterized molecules (Kowalewski, Huynh and Ray, 2021). This will allow future investigators to representatively sample the space of odorous molecules as well as identify previously unknown odorants with a target odor character. Here I put this work into the context of other modeling efforts and highlight the urgent need for large new datasets and transparent benchmarks for the field to make and evaluate modeling breakthroughs, respectively.

Mouse mandibular retromolar taste buds associated with a mucus salivary gland

We have characterized a recently rediscovered chemosensory structure at the rear of the mandibular mucosa in the mouse oral cavity originally reported in the 1980s. This consists of unorganized taste buds, not contained within troughs, associated with the ducts of an underlying minor salivary gland. Using whole-mount preparations of transgenic mice expressing green fluorescent protein under the promoter of taste-signaling-specific genes, we determined that the structure contains taste bud clusters and salivary gland orifices at the rear of each mandible, distal to the last molar and anterior to the ascending ramus. Immunohistochemical analysis show in the retromolar taste buds expression of the taste receptors Tas2R131 and T1R3 and taste cascade molecules TrpM5, PLCβ2, and GNAT3, consistent with type II taste cells, and expression of GAD1, consistent with type III taste cells. Furthermore, the neuronal marker CGRP in retromolar mucosa tissue wrapping around TrpM5+ taste buds was observed. RT-PCR showed that retromolar taste buds express all three mouse tas1r genes, 28 of the 35 tas2r genes, and taste transduction signaling genes gnat3, plcb2, and trpm5, making the retromolar TBs similar to other lingual and palate taste buds. Finally, histochemistry demonstrated that the mandibular retromolar secretory gland is a minor salivary gland of mucous type. The mandibular retromolar taste structure may thus play a role in taste sensation and represent a potential novel pharmacological target for taste disorders.

Olfactory-trigeminal interactions in patients with Parkinson’s disease

Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson’s disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: post-viral, sinunasal, post-traumatic and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile.We here review the literature on PD-specific chemosensory alteration patterns compared to NPOD. Specifically, we focused on the impact of PD on the trigeminal system and particularly on the interaction between olfactory and trigeminal systems. As this interaction is seemingly affected in a disease-specific manner, we propose a model of interaction between both chemosensory systems that is distinct for PD-related OD and NPOD. These patterns of chemosensory impairment still need to be confirmed in prodromal PD; nevertheless, appropriate chemosensory tests may eventually help to develop diagnostic tools to identify individuals at risks for PD.

Scent Marks Signal Species, Sex and Reproductive Status in Tamarins (Saguinus spp., Neotropical Primates)

Olfactory communication is an important mediator of social interactions in mammals, thought to provide information about an individual’s identity and current social, reproductive, and health status. In comparison with other taxa such as carnivores and rodents, few studies have examined primate olfactory communication. Tamarins (Callitrichidae) conspicuously deposit odorous secretions, produced by specialized scent glands, in their environment. In this study, we combined behavioral and chemical data on captive cotton-top tamarins, Saguinus oedipus, and bearded emperor tamarins, S. imperator subgrisescens, to examine the role of olfactory communication in the advertisement of species, sex, and reproductive status. We observed no difference in scent-marking behavior between species; however, females marked more frequently than males, and reproductive individuals more than non-reproductive ones. In addition, tamarins predominantly used their anogenital gland when scent-marking, followed by the suprapubic gland. We collected swabs of naturally deposited tamarin anogenital scent marks, and analyzed these samples using headspace gas chromatography-mass spectrometry. Despite a limited sample size, we established differences in tamarin anogenital mark chemical composition between species, sex and reproductive status, and identified 41 compounds. The compounds identified, many of which have been reported in previous work on mammalian semiochemistry, form targets for future bioassay studies to identify semiochemicals. Our non-invasive method for collecting deposited scent marks makes it a promising method for the study of olfactory communication in scent-marking animal species, applicable to field settings and for the study of elusive animals.