In mammals, the birth of olfactory sensory neurons (OSNs) occurs throughout life, presumably solely to replace damaged neurons. Each OSN precursor is thought to stochastically choose, out of hundreds of possibilities, a single odorant receptor gene, which defines the subtype identity of the mature OSN. Thus, neurogenesis in the olfactory epithelium (OE) is considered stochastic regarding subtype. Recently, however, we have found that the birthrates of specific OSN subtypes are accelerated by olfactory stimulation. These findings raise questions about the nature of the neurogenic stimuli and their relationship to the subtypes whose birthrates are altered that are critical for understanding the mechanism and function of this process. Using RNA-seq and scRNA-seq, we found evidence that OSNs of subtypes that detect male and/or musk odors are more abundant in mice exposed to male odors and can undergo stimulation-dependent neurogenesis. Based on these findings, we hypothesized that the stimuli that promote the birthrates of specific OSN subtypes are discrete odors that selectively activate the subtypes whose birthrates are accelerated. To test this, we exposed female mice to male-specific odors or muscone and then quantified the neurogenesis rates of the OSN subtypes that detect these odors using combined RNA Fluorescent in situ hybridization and EdU-birthdating. Our findings indicate that male-specific and musk odors selectively promote the birthrates of OSN subtypes that are activated by these odors. These results reveal that some discrete odors can selectively increase the neurogenesis rates, and therefore, representations of cognate OSN subtypes in the OE, and suggest that persistent neurogenesis may play an unknown adaptive function.

Childhood cancer survival rates have markedly improved in recent decades. Increased survival can be attributed to providing new therapies and more intensive treatment regimens. However, as a result, almost all children suffer from severe treatment-related side effects such as pain, nausea, and changes in appetite. Although frequently overlooked in clinical practice, taste changes occur in up to 60% of children with cancer and have been reported to be the third most common bothersome symptom. All these symptoms together can contribute to impaired nutritional status, which have been associated with more infections, worse survival, and poor quality of life. As previous studies relied on self-report, small samples, and did not include smell function, it remained unclear how, when, and among which types of childhood cancer chemosensory changes are experienced during treatment. Therefore, we conducted several studies in children with any type of childhood cancer including psychophysically measured smell and taste function (Sniffin’ Sticks and Taste Strips) and self-report (questionnaires and semi-structured interviews). We found that changes in smell and taste are very common but rather heterogeneous in its presentation. That is, smell and taste sensitivity can be either decreased or increased or perceived as completely different than before. In general, we conclude that smell sensitivity seems higher during treatment, specifically in children with acute lymphoblastic leukemia. In contrast, taste sensitivity seems lower during active treatment with chemotherapy. Moreover, most cases of taste loss were found among children with lymphomas and solid tumors specifically. During this talk, we will further share how children with cancer cope with these different types of chemosensory distortions.

Increasing acceptance of bitter stimuli is important for the health of pediatric patients who must consume bitter medicines or nutritional interventions. The aim of this study was to determine if children age six months to five years accept an amino acid (AA)-supplemented oral rehydration formula of our design that contains multiple bitter tasting AAs. These AAs can be clinically advantageous to the gastrointestinal tract, which could benefit children during acute diarrhea. Methods: Sodium chloride, sodium gluconate, zinc sulfate and sucralose were used to decrease bitterness and increase palatability. Participants were trained to give the solutions they liked to a plush toy of Big BirdTM and those they did not like to a plush toy of Oscar the GrouchTM. Participants were offered the solutions to drink and the volume consumed was also measured. Results: The addition of sodium chloride and zinc sulfate did not significantly increase acceptance of the solution. Participants rejected this solution equally to a negative control solution of quinine hydrochloride. Sodium gluconate and sucralose were added to the formulation and acceptance significantly increased (p<0.05). There was no significant difference in acceptance of the amino acid-based formula containing sodium chloride, sodium gluconate, zinc sulfate, and sucralose compared to the standard oral rehydration therapy or a comparably sweetened sucrose control solution. Participants drank and tolerated up to 80 mL of the bitter-reduced amino acid-based formulation in one 15 min sitting. Conclusion: This study demonstrates that pediatric participants will accept a bitter-reduced AA-based formulation of oral rehydration therapy, providing evidence that children are likely to accept this solution, which will be used in a clinical trial this year.

Previously, we showed that rat chorda tympani nerve responses and ultrastructural characteristics of fungiform taste pores changed with age. The effects of aging on the taste system in mice, the preferred model for chemosensory research, has been largely unstudied. The aim of this study was to examine whether aged mice had differences in taste preferences to sucrose, NaCl, and NH4Cl, and whether they had differences in ultrastructural characteristics of fungiform taste pores using scanning electron microscopy (SEM). Thirty-minute two-bottle preference tests indicated that preferences for NaCl and NH4Cl, but not sucrose, were significantly different in aged mice (16-17 months old) relative to young mice (5 months old). In the same animals, we found that the aged group had a significantly lower percentage of fungiform papilla with taste pores present. Microvilli of taste bud cells extend into the taste pores of fungiform papillae. The absence of a taste pore on fungiform papillae strongly suggests that taste stimuli cannot interact with taste bud cells beneath the epithelial surface and consequently decrease taste nerve activity. These findings are consistent with our recent findings in rats, where advanced aging had a significant impact on the magnitude of chorda tympani 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. While the morphological changes at the level of the fungiform taste pore in aged mice are might have played a role in differences in behavioral taste preferences to salt stimuli, it is possible that changes in central taste processing occur as well.

Have you ever experienced or heard from others that their taste preferences change as they age? Some people do experience changes in taste preferences because of aging. For example, you find that something you used to like is no longer salty enough.

A study by Kolbe M Sussman & Joseph M Breza from Eastern Michigan University may explain why our taste changes with age. Sussman and Breza used mice to compare the preferences for saltiness and sweetness to indicate how this changes across a lifespan. They found that mice in different age groups showed significantly different preferences for saltiness but not for sweetness. The researchers also found differences in the tongues of older mice, particularly in the key structures responsible for taste detection. Taste pores, which are located on fungiform papillae, are less abundant in aged animals.

The research suggests that a decrease in taste-detecting cells may be the reason for the perceived decrease in taste intensity with age. This could explain why our taste preferences change as we get older. The exciting implication of this finding is that future treatments targeting the tongue's receptors, the key structures responsible for taste detection, could potentially restore our sense of taste to a more youthful state!

After undergoing weight loss surgeries, most patients report “taste” changes. However, when we evaluated patients using validated sensory evaluation techniques, we found no changes in perceived taste intensity or sensitivity pre- to post-surgery. Because we assessed participants with pure gustatory stimuli in a fasting state, it is unclear if patients’ self-reported “taste” changes are due to retronasal smell/ “flavor” changes or are only manifested during the fed state. Using a cross-sectional study design, we compared sensory responses in women who underwent metabolic surgery 2-6 years ago (n=15) with a non-operated-BMI equivalent group (n=15) and a normal BMI group (n=15) over two visits: one fed and one fasted. Using a sip-and-spit method, women tasted solutions representative of basic taste qualities containing matching odorants (e.g., sucrose with strawberry extract) with and without nose clips. They used separate general labeled magnitude scales to rate their perceived intensity of taste, smell, flavor, and pleasantness. Results from mixed ANOVAs show that the surgery group rated smell intensity as stronger than the normal BMI group for all stimuli (p≤0.05); values in the non-operated-BMI equivalent group were intermediate between the other groups. However, all groups rated taste as equally intense and pleasant and displayed similar enhanced taste intensity when tasting samples without vs. with nose clips (p<0.001). Feeding conditions failed to affect intensity ratings. Our findings suggest that metabolic surgery is associated with perceiving a stronger intensity of retronasal smell without impact on taste perception and that feeding condition is unimportant for assessing taste or smell intensity perception in women.

Imagine you had weight loss surgery and people ask you if food tastes different afterwards. You might say yes, that things seem sweeter or maybe not as flavorful. But scientists wanted to see what was really happening to people's senses after weight loss surgery, not just rely on what people said. They did a taste test with several groups to better understand how weight loss surgery was affecting taste and smell. Here's the surprising part: When they tested pure taste (like sugar water), there wasn't much difference between any of the groups, whether they had surgery or not, or if they had eaten beforehand. However, there was a difference in smell! The women who had surgery seemed to smell things more strongly, especially when the taste and smell were mixed together (like strawberry-flavored sugar water). So, why do people who have weight loss surgery feel like things taste different? It seems like it might be more about how they smell their food, not necessarily how their taste buds work. It's kind of like when you have a stuffy nose and food seems bland – the taste is still there, but you can't smell it as well so it feels less flavorful.

Odorant receptors (ORs) are highly sensitive chemical receptors that respond to a diverse range of volatile compounds. While organisms relying on olfaction for survival possess remarkable abilities to detect trace chemicals, our current chemical sensing technology is inadequate in comparison. Recent studies have shown significant differences in the chemical profile of human breath between healthy individuals and those infected with pathogens such as malaria, tuberculosis, or COVID-19. Leveraging the unique chemical profiles associated with diseases could provide a robust method for disease detection. In this study, our objective is to engineer insect ORs to selectively activate in the presence of volatiles associated with diseases. Specifically, we focused on MhOR5, an odorant receptor from the Jumping Bristletail (Machilis hrabei), a basal insect that lacks the OR co-receptor (Orco) found in modern insects. MhOR5 is a well-characterized receptor with broad selectivity and an experimentally determined structure, making it an ideal candidate for targeted engineering. We expressed MhOR5 in a heterologous cell system using HEK293T cells and tested its response to disease-associated volatiles (DAVs). Through structural analysis, we identified key residues that potentially contribute to ligand selectivity, and tested mutations made at these residues for altered ligand selectivity. Our findings revealed distinct ligand selectivity among most mutants in response to individual DAVs. Additionally, we are developing a platform for high-throughput, non-biased screening of combinatorial mutants. This methodology will establish a solid foundation for engineering ORs with specificity towards particular chemicals and for developing engineered OR arrays for disease diagnosis.

Can we use insects to detect diseases? Current methods to detect diseases such as COVID-19 usually involve expensive and time-consuming biomedical techniques. But an intriguing alternative possibility has recently emerged: when people get sick, we breathe out odors that can be detected by animals, such as dogs or even honeybees (1,2).

While a swarm of bees flying around a hospital doesn’t seem like a great idea, Rhodry Brown and colleagues are taking advantage of recent breakthroughs in our understanding of how insects detect odors to design a more practical approach. They can predict how to alter the DNA sequence of an insect odorant receptor, called MhOR5, to better detect specific odors, including those from people with malaria, tuberculosis or COVID-19.

These results are an important step towards a better understanding of how odorant receptors bind volatiles and, ultimately, raise the prospect of building ‘artificial noses’ that could be installed in schools or airports to quickly screen people for infectious diseases.

References:

1. https://www.degruyter.com/document/doi/10.1515/jom-2023-0104/html
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096705/

Background—Racial and ethnic differences in taste perception may influence food preferences, diet, and medication adherence, impacting disease prevention, treatment, and health disparity. Difficulties recruiting from racial and ethnic minority populations may limit the understanding and application of these differences. Purpose—This study evaluates the recruitment approaches used by researchers to enroll participants of Sub-Saharan African (n=127) and Asian (n=154) into a bitter taste perception and medicine study. Methods—Recruitment occurred from January 2021 – December 2022 using five main recruitment strategies: 1) Paper Flyers 2) Paid Advertisements 3) Internet-based and social media outreach 4) Professional Networking 5) Personal Networking. Eligible participants were over 18 and identified as a 1st, 2nd, or 3rd generation immigrant. Results—The recruitment process extended beyond the anticipated timeline, and the effectiveness of strategies varied among the ancestry groups. Recruitment goals for individuals of Asian and European ancestry were met within the first year, with flyers and online advertisements being more successful in recruiting 52% of those participants. Recruiting participants of African ancestry required more intentionality and was not achieved until the second year, with 66% of participants recruited through professional and personal networking. Discussion—Sensory-based research may be key to understanding nutrition behaviors and disease risk; thus, adequate representation of diverse populations is necessary. Results suggest that researchers may have misunderstood fundamental differences when recruiting multi-ancestral groups. Limitations exist in understanding unique barriers and facilitators to research participation among different ethnic groups.

Taste bud cells undergo continuous turnover throughout life, relying strictly on innervation for replenishment. This nerve-dependent process was initially described over 150 years ago. Recently, our studies showed that R-spondin alone is sufficient to substitute for neuronal input to induce taste bud regeneration via its interaction with taste stem/progenitor cell-expressed receptor Rnf43/Znrf3. We provided evidence supporting the notion that R-spondin 2 (Rspo2) might be the elusive factor supplied by gustatory neurons that regulates taste stem cell activity. However, the essentiality of gustatory neuron-supplied Rspo2 in taste tissue maintenance remains unresolved. In this study, we aimed to determine the necessity of gustatory-supplied Rspo2 in taste tissue homeostasis through genetic approaches. We utilized a mouse line with the neomycin-resistance gene (NeoR) inserted into one of the intron regions of the Rspo2 gene, resulting in reduced Rspo2 expression. This led to a significant reduction in the number of taste buds in both the anterior and posterior tongue when compared to wild-type mice, with a gene dosage-dependent effect. Notably, this phenotypic change could be fully reversed by removing NeoR from the Rspo2 gene. Additionally, we employed Adeno-associated Virus-based delivery of the Cre recombinase in conjunction with a mouse line amenable to Cre-based ablation of Rspo2 exons encoding receptor binding domains. Our results demonstrate that the ablation of Rspo2 in the nodose-petrosal-jugular ganglion complex can lead to a nearly complete loss of taste buds in the circumvallate papilla. Thus, our study unequivocally establishes that Rspo2 is the elusive gustatory neuron-supplied factor that acts on taste stem cells to maintain taste tissue homeostasis.

Most volatile compounds entering the nasal cavity activate both olfactory sensory neurons and chemosensory trigeminal fibers, leading to olfactory and somatosensory (e.g., irritation) sensations. These systems interact at the peripheral and central levels, leading to a change in perceived intensity. To understand this interaction, we compared physiological and perceptual responses in mice and humans, respectively. We delivered varying concentrations of 2-phenethylalcohol (olfactory agonist) and CO2 (trigeminal agonist) and their mixtures in different ratios and recorded electro-olfactogram (EOG) responses in mice, and intensity ratings were recorded for humans. In mouse olfactory epithelia, CO2 /PEA mixtures induced EOG responses greater than the olfactory stimulus alone. In TRPA1/V1-knockout mice, which lack TRPA1, the trigeminal receptor for CO2, responses evoked by the PEA/CO2 mixture were not significantly different from those evoked by PEA alone. In humans, lower concentrations (10-20%) of CO2 increased the perceived intensity of the mixture, whereas higher CO2 concentrations overshadowed the contribution of PEA. Established odor intensity models do not predict this interaction. In summary, a trigeminal agonist modifies both neural and perceptual responses, and models of odor intensity need to account for this interaction.

When we smell something, tiny particles go into our nose and activate two different sensory systems. The olfactory system helps us detect odors, while the trigeminal system makes us feel spicy, cool (like mint) and irritation. These two systems work together making our perception of scents a complex sensory experience.

To learn how we perceive scents, scientists from the Monell Chemical Senses Center studied how the information from the two systems work together in mice and people.

They used two chemicals which can activate either one sensory system or the other: one that activates only the olfactory system and smells like rose, and carbon dioxide, which activates only the trigeminal system and causes a tingling or stinging feeling in the nose. These two were then combined together in different quantities in the experiments.

In mice, they measured the level of activation of the special cells which detect odors in the nose. They determined that these cells were more active when stimulated with a mix of the rose-smelling chemical and carbon dioxide than just using the rose-smell alone. However, in special mice in which the trigeminal system is unable to detect carbon dioxide, the activation of the odor-detecting cells did not increase. This indicates that, differently from what was previously thought, these sensory systems interact not only in the brain but also in the nose, where the activation of the trigeminal system enhances the response of the olfactory system to odors.

To understand how this process impacts final odor perception, they asked people to rate the odor intensity of either a mix of rose-like scent and carbon dioxide, or only rose-like scent. From the ratings collected, they concluded that small amounts of the tingling chemical made the rose-scent feel stronger, but when carbon dioxide was too much, reduced the scent intensity perceived, as the feeling of irritation in the nose would take over the overall sensory experience. In short, the trigeminal system can change how strong a smell feels, starting from the nose. As the trigeminal system is often overlooked, this study highlights its role in how people experience scents and gives us some insights on how these two sensory systems work together.

This research conducted by Aiden Streleckis, Robert Pellegrino, Matthew Andres, Johannes Reisert, Joel Mainland, and Federica Genovese was presented at the Association of Chemical Sciences (AChemS) 46th Annual Meeting in April 2024 at Bonita Springs, Florida. https://achems.org/2024/

Psychophysical tests are generally more sensitive and reliable in detecting and quantifying stimulus responses than behavioral testing of discrimination and recognition. In our previous work, with a “blast” style olfactometer (referred to as the sniff olfactometer) we are able to embed a 70ms odorant mixtures puff into the middle of deep inhales of greater than a second. Using perceptual data collected from human subjects across varied treatments using the sniff olfactometer (SO), we were able computed stable, reproducible logistic models. Based on the foundational components of the SO, our research group constructed a gustometer that uses the same coding and testing programming to operate peristaltic pumps as well as deliver 600ms pulses of tastants to the tip of the tongue. The data collected from the gustometer produced functional logistic models of taste perception within the same time frame as a deep inhalation during an SO measurement of odor recognition. These two delivery systems could be combined to study multimodal perception to quantitively determine the effects of tastants on odor perception. Preliminary tests have generated stable logistic functions for sucrose and “sweetness”, citric acid and “sour”, pyrazines and “toast”, hexanal and “grass”, methanethiol and “rotten cabbage”. This poster will present the computational results of odorants and tastants delivered simultaneously and asynchronously to discuss the implications for odor-taste processing such as suppression and enhancement.

Our senses of taste and smell work together to create experiences that are richer and more complex than the individual sensations alone. At Cornell University, researchers have developed innovative tools to explore how these senses interact. They created the “sniff olfactometer,” a device that delivers precise bursts of scent to the nose, and a “gustometer,” which provides controlled tastes to the tongue.

By combining these two devices, scientists can study how taste and smell influence each other. For instance, combining the smell of citrus with the taste of a citrus fruit acid may make the lemony scent stronger while reducing the sourness. This research is uncovering fascinating insights into how our senses combine to shape the flavors and aromas we experience every day. Understanding these interactions could lead to exciting new discoveries in food, fragrance, and beyond.

This research conducted by Tiffany Hsu, Yao Jiang, Leto Solla, Jing Wu, Milan Poland, Robin Dando, and Terry Acree at Cornell University was presented at the Association of Chemical Sciences (AChemS) 46th Annual Meeting in April 2024 at Bonita Springs, Florida.