41st Annual Meeting of the Assocation for Chemoreception Sciences

Printable Program & Abstracts

April 14-17, 2019
Bonita Springs, FL

Monday, April 19, 2021

10:00 - 12:00 PMPlenary Room 1
Welcome & Keynote Lecture

Welcome By Achems 2021 President
Linda Barlow
University of Colorado Anschutz Medical Campus

Program Highlights
Max Fletcher
The University of Tennessee Health Science Center

Awards Ceremony
Nirupa Chaudhari
University of Miami

Keynote: Mouse Facial Expressions Reflect Emotions And Reveal Subjective Value
Nadine Gogolla
Max Planck Institute of Neurobiology

Questions & Answers

1:00 - 3:00 PMParallel Room 1
Cell Types in Taste Buds and Tentacles

Chair(s): Thomas Finger

Cell Types In Taste Buds And Tentacles
Thomas Finger, Sue Kinnamon
Rocky Mtn. Taste & Smell Ctr. / U. Colo Med Sch, Aurora, CO, United States

This symposium will discuss the current thinking about the diversity of cells within taste buds and chemotactile sensory organs of octopus suckers.  While octopus suckers may seem an odd juxtaposition, both taste buds and sucker chemosensory receptor cells share the property of being contact chemosensory organs responsive to sapid chemical cues crucial for eliciting feeding. Both sucker chemotactile sensory organs and taste buds possess different morphological types of receptor cells that correlate with different functional properties. Vertebrate taste buds are classically described as possessing 3 types of elongate taste cells yet recent studies suggest additional cell types exist and raise the question of how to define cell types in any chemoreceptor system.

Non-Canonical Cell Types In Taste Buds
Kathryn Medler
University at Buffalo, Buffalo, NY, United States

The peripheral taste system uses distinct signaling pathways to detect chemicals in potential food items. These signaling pathways are currently thought to be expressed in specific subsets of taste cells with no overlap between them.  Bitter, sweet and umami stimuli have complex chemical structures and activate G protein coupled receptor (GPCR) pathways in Type II cells while salt and sour are detected by ionotropic receptors in Type III cells.  The canonical taste model states that bitter, sweet, and umami stimuli are transduced by Type II taste cells using GPCRs and a common PLCβ2/IP3R3/TRPM5 signaling pathway. We demonstrated that TRPM4 also has an important role in this pathway and is required for the normal transduction of these stimuli.  More recently we identified a new population of taste cells that respond to multiple taste qualities including bitter, sweet, sour, and umami, which we termed Broadly Responsive (BR) cells. Using live cell Ca2+ imaging in isolated taste cells and transgenic mice, we determined that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ3 signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Behavioral assays and analysis of the nucleus of the solitary tract (NTS) confirm that functional Type II and BR cells are both required for normal taste responses to bitter, sweet and umami stimuli.  These data, along with other recent studies, reveal that the taste bud contains non-canonical taste cells that have critical roles in the transduction of multiple taste stimuli.  

Salt-Responsive Cells &Ndash; A Unique Cell Type?
Akiyuki Taruno1,2
1Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, *, Japan, 2JST PRESTO, Saitama, *, Japan

Of the five basic tastes – sweet, umami, bitter, sour, and salty –, the least understood is salty taste comprising two pathways: sodium taste and high salt taste. Sodium taste mediates behavioral attraction to sodium salts, whereas high salt taste mediates aversion to high concentrations of various salts. The epithelial sodium channel (ENaC) has been established as the Na+ sensor in taste cells dedicated to sodium taste, which we can refer to as sodium cells. High salt taste reportedly recruits bitter- and sour-sensing taste cells; however, the identity of sodium cells and their intracellular signal transduction cascade were unclear until recently. We identified taste cells expressing ENaC and CALHM1/3 as sodium cells, whereby the entry of oral Na+ elicits suprathreshold depolarization for action potentials driving voltage-dependent neurotransmission via a channel synapse involving the CALHM1/3 channel. Each taste bud is considered to consist of three distinct cell types: I, II, and III. To which taste cell type do sodium cells belong? Expression analyses of cell-type marker proteins suggested that sodium cells do not belong to any of the known taste cell types. Remarkably, however, sodium cells and type II cells share the CALHM1/3 channel synapse whose structure has been considered the most characteristic morphological feature of type II cells. Thus, the identification of sodium cells defines a previously unidentified taste cell population, and questions the current criteria of taste cell classification. I will discuss recent data on molecular and functional properties of sodium cells to provide a framework for refining taste cell classification.

Molecular Basis Of Chemotactile Sensation In Octopus
Lena van Giesen, Peter Killian, Corey Allard, Nicholas Bellono
Harvard University, Cambridge, MA, United States

Octopuses are voracious hunters that search the seafloor for hidden prey using their eight flexible arms. These arm behaviors are supported by a peripherally-distributed nervous system to sense and capture prey inaccessible to traditional sense organs. The sensory receptors employed to mediate these behaviors in cephalopods were unknown. Our investigation in this virtually unexplored ‘touch-taste’ sense led to the discovery of a novel family of chemotactile receptors (CRs) that mediate the octopus’ contact-dependent, aquatic chemosensation CRs are found specifically in cephalopods, expressed in suction cups (suckers) along the arms, and mediate the detection of poorly-soluble terpenoid molecules from natural products which act as ‘touch-taste’ stimuli in aquatic environments. CRs are co-expressed in diverse patterns and form heteromeric ion channel complexes to specify signal detection and transduction, a filtering system suited to the octopus’ uniquely-distributed nervous system. Furthermore, separate chemo- and mechanosensory cells express specific receptors and exhibit discrete electrical activities to encode chemical and touch information, respectively.

Cannonical Cell Types In Mouse Taste Buds
Courtney E Wilson1,2,3
1University of Colorado School of Medicine Department of Otolaryngology, Aurora, CO, United States, 2University of Colorado School of Medicine Department of Cell and Developmental Biology, Aurora, CO, United States, 3Rocky Mountain Taste and Smell Center, Aurora, CO, United States

Early ultrastructural studies of mammalian taste buds identified three main taste cell types: Type I, II, and III taste cells. These categories have since been associated with distinct physiological and molecular features. Type I cells wrap around neighboring cells, and express molecular components that may degrade or take up neurotransmitters released from other cell types. In those ways, Type I cells may function as astrocyte-like support cells for Type II and III taste cells. Type II cells express receptors for bitter, sweet, or umami taste qualities, and release ATP as a neurotransmitter via unique channel synapses to activate P2X receptors on the gustatory nerve fibers. Many Type III cells express the proton channel OTOP1 and are thus responsive to acids. Unlike Type II cells, Type III cells transmit this information to nerve fibers via conventional vesicular synapses. As our body of knowledge regarding these cells grows, however, the lines between these cell categories have been somewhat complicated. Multiple cell types may be involved in the transduction of salty stimuli, and some taste cells may respond to multiple taste modalities. Anatomically, we find ultrastructural features that blur the lines between canonical cell types. Type III cells occasionally contain characteristics of channel synapses, which are canonically confined to Type II cells. Rarely, Type II cells contain atypical mitochondria that abut Type I cells, rather than nerve fibers. Type I cells share relationships with innervating nerve fibers that, while not fitting into a known synaptic structure, may nonetheless be important points of communication between the taste bud and afferent nerves. As we uncover more details of taste bud function, we may find that taste cells fit better on a spectrum than into distinct types.

1:00 - 3:00 PMParallel Room 2
Satiety-based modulation of chemosensory processing across organisms

Chair(s): Thorsten Kahnt

Shifts In Food Preference Following Selective Pre-Feeding Depend On An Intact Orbitofrontal Cortex
Matthew PH Gardner1,2, Jessica C Conroy1, Davied Sanchez1, Jingfeng Zhou1, Geoffrey Schoenbaum1,3,4
1NIDA Intramural Research Program, Baltimore, MD, United States, 2Department of Psychology, Concordia University, Montreal, QC, Canada, 3Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University, Baltimore, MD, United States, 4Departments of Anatomy & Neurobiology and Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States

Food preferences rely on a multitude of factors and are highly dependent on the current state of an organism. Many studies have indicated that preferences not only rely on general homeostatic regulatory states such as thirst and hunger, but can also vary depending on the chemosensory-specific features of recently consumed foods or fluids. This finding implies that decisions about what to consume rely on latent complex chemosensory representations of recently experienced stimuli. Although several recent studies have indicated that primary cortical chemosensory regions such as the gustatory cortex can exert direct control over decisions, other research has suggested that frontal regions, such as the orbitofrontal cortex (OFC) are required for decision-making more broadly. Recent work in humans has indicated that OFC is required for shifts in choices based on changed food preferences following sensory-specific satiety; i.e., extensive pre-feeding of a specific food such as roast beef. Using a choice task in which rats are required to make decisions by integrating the amount and type of food available for different options, we found that OFC is necessary for choice behavior when food preferences shift due to this type of sensory-specific pre-feeding. Surprisingly, OFC was not required for behavior on this multi-feature choice task when preferences remained static. This finding implies that OFC is uniquely necessary for food choices when latent specific chemosensory representations must be incorporated into the decision.    

Satiety-Based Modulation Of Chemosensory Processing Across Organisms
Thorsten Kahnt, Laura Shanahan
Northwestern University Feinberg School of Medicine, Chicago, IL, United States

It is well-appreciated that chemosensory perception and feeding behaviors are modulated by satiety, metabolic state, and body weight via central and peripheral brain mechanisms. The goal of this symposium is to bring together researchers who are seeking to understand these complex interactions at complementary levels through their work in organisms ranging from invertebrates to primates. Dennis Mathew will present data on how anorectic peptides modulate the function of olfactory neurons across satiety states in Drosophila larvae, and how dysregulation of peripheral mechanisms influences feeding behavior and animal physiology. Matthew Gardner will present data on how satiety-related changes in choice behavior for food depend on the orbitofrontal cortex. Maia Pujara will discuss findings on how interactions between orbitofrontal cortex and amygdala bias behavior when food palatability changes in nonhuman primates. Finally, Laura Shanahan will present work on how satiety influences perceptual decision-making and neural responses to food odors in humans. Together, these speakers will provide an overview of recent research on how satiety impacts chemosensory behavior in different species and the neural mechanisms driving satiety-dependent changes. By exploring this topic from a cross-species perspective, the symposium will highlight parallels in chemosensory processing across organisms, from simple to complex.

A Preliminary Investigation Of Flavor-Nutrient Conditioning On Decision-Making And Autonomic Arousal In Rhesus Macaques
Maia Pujara1,2, Jaewon Hwang1, Nicole Ciesinski1,3, Charday Long1, Dawn Lundgren1, Elisabeth Murray1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, 2Sarah Lawrence College, Bronxville, NY, United States, 3Temple University, Philadelphia, PA, United States

Flavor-nutrient conditioning (FNC) elicits increased pleasantness ratings in humans and consumption in rodents for noncaloric fluids. Either amygdala (AMY) or orbitofrontal cortex (OFC) damage in monkeys disrupts flexible shifts in stimulus choice, but not consumption, following decreases in reward value. We adapted a paradigm developed in humans to test the causal role of OFC-AMY interactions in a decision-making task following selective FNC. All monkeys learned that two stimuli predicted two unique and equally preferred fluids. Monkeys then consumed the fluids, only one of which contained maltodextrin, used to increase the caloric content of one of the fluids and thus the reward value of the fluid selectively. Following conditioning, monkeys were evaluated for choices and pupil responses, as a measure of anticipatory arousal of reward. We also measured consumption of the two fluids before and after conditioning as a ‘proof of concept’ of the FNC manipulation. First, we predicted that all monkeys would show increased consumption of the fluid that was selectively paired with maltodextrin during conditioning. Second, we anticipated that monkeys with OFC x AMY lesions (n=4) would be impaired in making adaptive stimulus choices after increases in fluid value due to FNC. Third, we predicted that pupil size during stimulus presentation would track with the shift in expected reward value and that this would be positively correlated with choice for controls (n=5), but not for the lesioned group. All monkeys showed increased consumption of the conditioned fluid. However, this did not translate to a significant increase in choice or pupil size for the stimulus that predicted the conditioned fluid. Follow-up studies will address the factors affecting choice behavior and autonomic arousal following FNC.

How Satiety Modulates Perceptual Decision-Making In Olfactory Circuits
Laura K Shanahan1, Surabhi Bhutani1,2, Thorsten Kahnt1
1Northwestern University, Chicago, IL, United States, 2San Diego State University, San Diego, CA, United States

Prior work in both animals and humans suggests that food intake and odor perception are closely linked. For instance, multiple studies have shown that food odors are perceived as less pleasant in the sated state. However, whether and how satiety shapes olfactory perceptual decision-making remains unclear. To address this gap, we developed a novel olfactory decision-making task using binary odor mixtures. The mixtures consisted of food and non-food components (e.g., pizza and pine). On each trial of the task, human participants (n = 30) had to decide which component was dominant in the mixture. Participants completed the task before and after an odor-matched meal (e.g., pizza) so we could compare olfactory choices across hungry and sated states. We found that participants were less likely to select the meal-matched food odor as dominant in the sated state. This behavioral change could serve to facilitate olfactory decision-making by dampening food-based cues when they are least relevant (i.e., when sated). We also acquired functional magnetic resonance imaging (fMRI) data while participants engaged in olfactory decision-making to investigate the underlying neural mechanisms. We found that food intake influences odor-evoked fMRI ensemble patterns in olfactory cortex. Specifically, in the sated state, (1) activity patterns evoked by food and non-food odors were less discriminable for meal-matched odors, and (2) activity patterns evoked by odor mixtures were less food-like for the meal-matched odor pair. Moreover, we observed state-dependent differences in functional connectivity between olfactory cortex and insula. Our work reveals how satiety state modulates olfactory decision-making in the human brain, and may have important implications for health and nutrition. 

Analysis Of Starvation-Dependent Modulation Of Olfaction Using The Drosophila Larva.
Eryn Slankster1, Roshni Jain2, Dominique Baria1, Brianna Dailey-Krempel1, Seth Odell3, Dennis Mathew1,2,3
1Department of Biology, University of Nevada, Reno, NV, United States, 2Cell and Molecular Biology Graduate Program, University of Nevada, Reno, NV, United States, 3Integrated Neuroscience Graduate Program, University of Nevada, Reno, NV, United States

Starvation modulates an animal’s sensitivity to food odors. A widely-accepted model is that during the animal’s starved-state, lower insulin signaling leads to enhanced odor sensitivity and attraction to food odors. The model implicates NPF (fly ortholog of Neuropeptide Y) as a downstream target of insulin signaling. However, it does not account for the mechanisms by which insulin signaling changes odor sensitivity and behavior. We examine how insulin signaling mediates the starvation-dependent modulation of olfactory sensory neurons (OSNs). We hypothesize that insulin signaling impacts gene expression of downstream targets to influence neuron function. We take advantage of the fruit fly Drosophila melanogaster larva as a model system, which allows incisive molecular genetic analyses of olfactory neurons and their functions. Using an innovative molecular technique established in our lab, we show that insulin signaling in OSNs affects the transcription of Rutabaga (Rut) and Synaptotagmin1 (Syt1), two downstream target genes. Next, we show that domeless, a receptor for leptin, also expresses in OSNs. Our evidence suggests that leptin and insulin signaling pathways interact within OSNs. However, it remains unclear why OSN-modulation requires multiple anorectic signaling mechanisms. Finally, we show that manipulating the insulin signaling pathway in OSNs impacts larval feeding behavior and body weight. Our results build upon the prevailing OSN modulation model and highlight opportunities to understand better OSN modulation mechanisms and their relationship to animal physiology.  This project will generate new hypotheses and tools for the neuroscience community to understand how the internal contexts in which foraging decisions are made shape decision-making strategies.

4:00 - 6:00 PMPlenary Room 1
Presidential Symposium

6:00 - 8:00 PMPoster Hall
On Demand Poster Session #1

Tuesday, April 20, 2021

9:00 - 11:00 AMPoster Hall
On Demand Poster Session #2

11:00 - 1:00 PMParallel Room 1
Development of Chemosensation and Perception

Chair(s): Arianna Maffei

Development Of Chemosensation And Perception
Arianna Maffei1, Hillary Schiff1, Claudia Lodovichi2, Joost Maier3, Bianca Jones Marlin4
1Stony Brook University, Stony Brook, NY, United States, 2University of Padova, Padova, *, Italy, 3Wake Forest School of Medicine, Winston-Salem, NC, United States, 4Columbia University, New York, NY, United States

Postnatal development typically represents a period of heightened plasticity during which experience and learning refine neural circuits. There is surprisingly little information about how chemosensory experience may influence neural circuit function and limited knowledge about the mechanisms regulating postnatal plasticity of gustatory and olfactory circuits. Emerging research has recently begun to address these questions directly. This symposium will bring together researchers investigating postnatal development of gustatory and olfactory systems, and will showcase novel results highlighting the importance of early experience and learning in neural circuits for chemosensory processing. The topics covered in the presentation cover a broad range of topics including investigation of homeostasis and neurogenesis in the olfactory bulb (Dr. Claudia Lodovichi, University of Padova), postnatal development in the neural circuit from the bulb to the piriform cortex (Dr. Joost Maier, Wake Forest University), epigenetic regulation of olfactory cues (Dr. Bianca Jones Marlin, Columbia University), and discussion of a newly identified critical period for experience-dependent plasticity in the gustatory cortex (Dr. Hillary Schiff, Stony Brook University). As research in this field gains a foothold, this symposium will offer an invaluable opportunity for assessing the state of the field, highlight important open questions and suggest possible directions for future work.

Early Postnatal Development Of Information Processing In Bulbo-Cortical Circuits
Joost X. Maier, Zihao Zhang, D. Chad Collins
Wake Forest School of Medicine, Winston Salem, NC, United States

Most animals must start to interact with their environment long before neural circuits have fully matured. However, information processing in neonatal brains remains poorly understood. The rodent olfactory system offers a unique opportunity to study neonatal information processing given its experimental tractability and the importance of odor perception for survival in early life. We performed extracellular recordings of network-level local field potential activity in the piriform cortex of unanesthetized rat pups ranging in age from several hours to three weeks after birth. We found that neonatal olfactory (piriform) cortex exhibits highly structured spontaneous and odor-evoked oscillations (respiration-driven slow oscillations with nested spindle oscillations). Oscillatory activity patterns remain stable during the first two weeks of life, after which they undergo rapid, quantitative changes to a mature state. Simultaneous recordings from the olfactory bulb suggest that oscillations originate in the bulb, and acute lesions of bulbo-cortical connectivity suggest that they are sustained by corticofugal feedback projections. Thus, neonatal olfactory processing is characterized by stable network-level activity patterns, despite known changes at the cellular and molecular levels. Moreover, neonatal activity patterns share characteristics with activity patterns previously observed in adults, and are generated by overlapping neural circuits. These findings stand in contrast with previous findings from sensory neocortex, where neonatal information processing is characterized by developmentally transient circuits and activity patterns, and may reflect the integral role of olfaction in guiding adaptive behavior from the time of birth.

Bridging The Gap Between Innate And Learned Behaviors: A Parent&Rsquo;S Role In Promoting Survival
Bianca Jones Marlin, Richard Axel
Columbia University in the City of New York, New York, NY, United States

My research investigates the relationship between the innate and the learned. I have examined how an organism unlocks an innate behavior at the appropriate time i.e.-maternal instinct, and how a traumatic experience is passed to subsequent generations via paternal lineage. Changes in gene expression, and consequent behavior, of a parent, may permit offspring to exhibit an inherited adaptation to the environment. This process, known as the transgenerational epigenetic inheritance of environmental information, remains a complex mystery. Novel experiments performed by myself and others have demonstrated that odors in the environment of a mouse associated with aversive consequences result in compensatory alterations in the olfactory system of their offspring. I combine neural imaging, behavior, and molecular genetics to understand the transfer of information inherent in neurons of the parent, through the gamete, to neurons of their offspring. Our goal is to uncover the process through which learning and emotion in one generation can be transmitted not culturally, but rather biologically through DNA. We believe understanding how a learned behavior in the parent can essentially become an innate behavior in the offspring will have profound implications in societal health and well-being.  

Cl Homeostasis And Neurogenesis In The Olfactory System.
Andrea Maset1,2, 3, , Luisa Galla3, 4, Simona Francia1, 5, Olga Cozzolino6, 7, Paola Capasso8, Rosa Chiara Goisis3, 4, Gabriele Losi 3, 4, Angelo Lombardo8, 9, Gian Michele Ratto6, 7, Claudia Lodovichi1, 2, 3, 4
1Veneto Institute of Molecular Medicine, Padova, *, Italy, 2Padova Neuroscience Center, Padova, *, Italy, 3Department of Biomedical Sciences, University of Padua, Padova, *, Italy, 4Neuroscience Institute, National Research Council, , Padova, *, Italy, 5Center for Synaptic Neuroscience and Technology, Genova, *, Italy, 6 Istituto Nanoscienze, Consiglio Nazionale delle Ricerche, Pisa, *, Italy, 7National Enterprise for nanoScience and nanoTechnology, Scuola Normale Superiore, Pisa, *, Italy, 8San Raffaele Telethon Institute for Gene Therapy, IRCCS , Milano, *, Italy, 9Vita-Salute San Raffaele University, , Milano, *, Italy

Neuronal information processing results from the interplay between excitation and inhibition. Mounting evidence indicates that inhibition is essential in shaping spontaneous and evoked activity. Consistent with this prime role, alterations of inhibitory circuits exert a key role in the etiopathogenesis of several neurological diseases. The polarity of the responses (hyperpolarization versus depolarization) elicited by GABA, the major inhibitory neurotransmitter of the brain, is, however, not univocal but depends critically on the intracellular Cl- concentration that is regulated by specific Cl- cotransporters, whose expression is developmentally regulated. Immature neurons express mostly NKCC1 that favors high intracellular Cl- concentration and depolarizing responses. Mature neurons express mostly the cotransporter KCC2 leading to low intracellular Cl- concentration, and inhibition. The majority of inhibitory interneurons are generated during embryonic life, but a niche of neurogenesis persists in postnatal life in most mammals including human infants. These postnatally generated inhibitory interneurons are thought to play a key role in postnatal developmental plasticity, which is essential for normal brain development. Alterations of this process could therefore account for sensory and cognitive dysfunctionalities associated with neurodevelopmental disorders. Combining 2 photon imaging, electrophysiology, and quantitative anatomy, we have analyzed the impact of Oligophrenin 1 (OPHN1), a gene associated with intellectual disability- autism, on postnatal neurogenesis of forebrain GABAergic inhibitory interneurons, in mice carrying a null mutation in OPHN1. Here, I will present the results we found and the new research lines that emerged from these results.

A Critical Period For The Development And Expression Of Sucrose Preference
Hillary C Schiff, Maria Isaac, Alfredo Fontanini, Arianna Maffei
SUNY - Stony Brook Department of Neurobiology & Behavior, Stony Brook, NY, United States

Taste preferences are critical for survival as they direct consummatory behavior toward nourishing food and away from harmful substances. At the transition from relying on mother’s milk to foraging for food, animals experience a variety of new tastes and learn relevant information associated with consuming them. It is believed that these experiences shape the regions of the brain involved in taste processing during this postnatal period, thereby influencing gustatory preferences throughout life. The effects of early experience on taste preference and the maturation and function of the gustatory cortex (GC) have not yet been the subject of investigation. Here, we report that taste experience at weaning, but not in adulthood, affects preference for sweet tastes later in life. Using a brief access test, we observed that sucrose preference is enhanced in mice following exposure to a variety of tastants at weaning compared to mice exposed only to water and chow. Mice undergoing the same exposure at 8 weeks did not show differences in sucrose preference compared to their naïve littermates. The change in sucrose preference did not depend on familiarity with sucrose. Early exposure affected the maturation of inhibitory circuits in GC, marked by an acceleration of the association of parvalbumin expressing (PV+) neurons with perineuronal nets (PNNs) and an increase in the frequency of spontaneous inhibitory currents (sIPSCs) onto excitatory neurons. Enzymatic degradation of PNNs locally in GC in adult mice restored sensitivity to taste exposure. These results point to the presence of a critical period when experience may cause long-term changes in taste preference and to a central role for PV+ neurons and their association with PNNs in the experience-dependent modulation of taste preference.

11:00 - 1:00 PMParallel Room 2
Chemosensory Dysfunction in COVID-19: Behavioral and Neurobiological Factors

Chair(s): Shima Moein

Machine Learning: A Path Toward Optimized Smell Tests For Screening Covid-19
Richard L Doty
Smell & Taste Center, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Coronavirus Disease 2019 (COVID-19) continues to negatively impact families, health care facilities, and economies throughout the world. Among the symptoms of COVID-19 is a sudden decrease in smell function, making such dysfunction an early disease biomarker. Unfortunately, a significant number of persons with COVID-19 are unaware of their smell problem until being objectively tested.  Practical, sensitive, and inexpensive smell tests have the potential for rapid identification of carriers of the SARS-CoV-2 virus responsible for this disease so that early quarantine and medical treatment can be instituted.  In this study, we employed and evaluated eight sophisticated machine learning methods to identify unique multiple practical subsets of UPSIT odorant items sensitive to COVID-19 that can be used in sequential sets. As a trade-off between computing time and completeness of the search space, we modified a sequential selection strategy to consider at each iteration all combinations of 2-3 odorant features.  AdaBoost, an ensemble learning method combining multiple decision trees, achieved the best performance in all metrics, with an accuracy of 94.1%, sensitivity (true positive rate) of 93.5%, and specificity (true negative rate) of 94.7%. Logistic Regression and k-Nearest Neighbor (kNN, k=3 with city block distance metric), and Linear Discriminant Analysis methods had a slightly worse performance than Adaboost. Based on these and other considerations, a minimum of 10 odorant items was needed to achieve >85% sensitivity and specificity.

Chemosensory Dysfunction In Covid-19: Behavioral And Neurobiological Factors
Shima T Moein1, Richard L Doty2, Valentina Parma3, Jonathan Overdevest4, Carol Yan5
1School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, *, Iran, 2Smell & Taste Center, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Psychology, Temple University, Philadelphia, PA, United States, 4Department of Otolaryngology Head and Neck Surgery, Columbia University Medical Center, New York, NY, United States, 5Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA, United States

In early March of 2020, reports appeared in the social media of many countries linking smell/taste loss to the spread of SARS-CoV-2. Such reports led to studies of the prevalence and reversibility of the smell loss of COVID-19 and the cellular mechanisms responsible for the loss. These studies have the potential to play a significant role in early COVID-19 detection and the development of preventative interventions and therapies for COVID-19. In this symposium, the olfactory and gustatory manifestations of COVID-19 will be reviewed. Dr. Parma will discuss how a global consortium approached this issue in COVID-19 patients in over 60 countries. She will address the prevalence of chemosensory loss and its continued presence in various groups of patients. Dr. Overdevest will present the evolution in investigations to identify molecular pathways that are dysregulated during COVID-19 infection through a histopathologic and transcriptomic evaluation of post-mortem nasal epithelium biopsies.As the pandemic continues despite containment and mitigation strategies, even a low percentage of patients with sustained smell loss and other problems may challenge health systems. Dr. Yan will discuss the implications of smell loss, its assessment, and its management in the clinic. Moreover, challenges for clinicians to minimize its long-term effects on physical and mental health, including quality of life, will be addressed.Finally, Dr. Doty will explain how machine learning techniques are being used to optimize the sensitivity of smell tests to detect COVID-19. Such tests have the potential to provide a sensitive and inexpensive means for detecting persons carrying SARS-CoV-2 early in the COVID-19 disease process, as well as for tracking their function over time.

Treating Covid-19 Patients With Smell Loss In The Otolaryngology Clinic: Approach, Management And Prognosis
Carol / H Yan
University of California, San Diego Division of Otolaryngology- Head and Neck Surgery, Department of Surgery, San Diego, CA, United States

A full year has passed since patients were first seen in their medical and otolaryngology clinics with reported acute onset and often profound smell and taste loss that were soon linked to the SARS-CoV-2 virus. While studies vary in their prevalence, roughly 50% of patients with COVID-19 are estimated to suffer from viral-induced chemosensory dysfunction with approximately 5-25% experiences some extent of persistent smell and/or taste loss. The widespread screening of COVID-19 has allowed for a heightened clinical awareness in the early onset of one’s olfactory dysfunction with a known viral etiology. Despite the high spontaneous recovery rate, persistent smell loss and qualitative olfactory dysfunctions such as parosmias have developed in an unfortunate subset of COVID-19 patients. Thus, consideration for early onset therapy may be appropriate and physicians have the opportunity to recommend treatment options for acute and chronic COVID-19 associated olfactory loss. Preliminary studies have suggested efficacy with the use of olfactory training as well as topical and oral steroids for olfactory loss, and topical sodium citrate for qualitative olfactory symptoms. Early longitudinal data have also suggested that the increased severity of smell dysfunction and the female gender may predispose to long term olfactory loss. Perhaps equally as important as the therapeutic management of smell loss is the counseling provided and the understanding of the impacts of olfactory dysfunction on quality of life and mental health. In this symposium talk, we will review the literature and discuss the approach and management that an otolaryngologist might provide to patients suffering from acute and chronic COVID-19 related olfactory loss.

Molecular Underpinnings Of Olfactory Dysfunction Following Sars-Cov-2 Infection
Marianna Zazhytska1, Albana Kodra1, Daisy A. Hoogland2, John Fullard2, Hani Shayva3, Arina Omer2, Stuart Firestein1, Peter D. Canoll1, Panagiotis Rousos2, Benjamin TenOever2, Stavros Lomvardas1, Jonathan B. Overdevest1
1Columbia University, New York, NY, United States, 2Icahn School of Medicine at Mt Sinai, New York, NY, United States, 3Baylor Genetics, Houston, TX, United States

Olfaction is a closely coordinated partnership between odorant flow and neuronal signaling. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, and yet, decoding the mechanism behind this abrupt sensory deficit remains elusive. Patients with COVID-19 lack symptoms of nasal congestion and rhinorrhea present in many upper respiratory tract infections that result in a conductive reduction in an ability to perceive smells. To investigate the molecular underpinnings of SARS-CoV-2 related smell loss, we performed molecular analysis, including scRNAseq, RNA-FISH, and Hi-C on both human and syrian golden hamster olfactory epithelium. Here, we report that smell loss may be attributable to non-cell autonomous mechanisms that induce genomic compartment dysregulation and subsequent downregulation of critical signaling pathways responsible for production of olfactory receptors.

2:00 - 4:00 PMPlenary Room 1
Oral Abstract Session #1

4:30 - 6:30 PMPlenary Room 1
Polak Award Symposium

Wednesday, April 21, 2021

9:00 - 11:00 AMPoster Hall
On Demand Poster Session #3

11:00 - 1:00 PMPlenary Room 1
Oral Abstract Session #2

1:30 - 3:30 PMPlenary Room 1
Oral Abstract Session #3

4:00 - 5:00 PMPlenary Room 1
Don Tucker Award Finalists

5:30 - 7:30 PMPlenary Room 1
Career Networking Social

Thursday, April 22, 2021

9:00 - 11:00 AMPoster Hall
On Demand Poster Session #4

11:00 - 12:00 PMPlenary Room 1
Business Meeting

12:30 - 2:30 PMPlenary Room 1
Oral Abstract Session #4

3:00 - 4:00 PMPlenary Room 1
Undergraduate Award Finalists

4:30 - 6:30 PMPlenary Room 1
Awards Lectures 2020

Friday, April 23, 2021

9:00 - 11:00 AMParallel Room 1
The Cure for Olfactory Loss

Chair(s): Thomas Hummel

Restoring Olfaction: From Current Paradigms To Olfactory Implants
Moustafa Bensafi
CRNL-CNRS, Lyon, *, France

Olfactory deficit influences several aspects of quality of life (ex. relationship to food, social interactions). Surgical and pharmacological treatments, and olfactory training are possible therapies. However, when these treatments fail, artificial systems assisting individuals with olfactory loss in their daily life could be a promising therapeutic alternative. Artificial noses are increasingly used in industry for specific needs (ex. quality control) but they are not made available for people with olfactory loss. How they could be useful in patients with smell deficits is still an open question. The present conference will present data from the literature combined with experimental data showing the latest technological developments in artificial olfaction. We will discuss how these technologies can be applied to the field of olfactory deficits, and how patients perceive the usefulness of such prostheses or implants of the future.

Achems Clinical Symposium:The Cure For Olfactory Loss
Thomas Hummel
Smell and Taste clinic, Dept. of ORL, TUD, Dresden, *, Germany

The corona pandemic made it painfully clear to a broader public that there are limited options for the treatment of olfactory loss. Hence, the title of the symposium is provocative. Having said this, major advances in the understanding of olfactory loss have been made during the alst 20 years. Several options for treatment have been investigated, so that their possibilities and limitations are now clearer. The symposium will almost exclusively include presentations from medical doctors who see patients with olfactory loss on a daily basis. Speakers come from the USA, the UK and France, and all of them are widely recognized researchers. First, Katie Whitcroft form London will talk about corticosteroids which are the most frequently used drugs in the treatment of olfactory loss. Vijay Ramakrishnan from Aurora will deal with the nasal microbiome which may play a major role in olfactory loss. Andrew Lane from Baltimore will then talk about most recent advances in the understanding of the mechanisms of olfactory loss associated with inflammatory conditions – which are the cause of approximately 2/3 of all olfactory disorders, apart from aging. Finally, Moustafa Bensafi from Lyon will shed light on current developments in new therapeutic options including olfactory implants.

Inflammation And Olfactory Function
Andrew Lane
Johns Hopkins School of Medicine, Baltimore, MD, United States

The anatomic location of the olfactory epithelium (OE) makes it vulnerable to damage from infectious and non-infectious agents.  The remarkable capacity for OE regeneration allows the sense of smell to be maintained in this challenging environment.  A critical component of injury and repair mechanisms at mucosal surfaces is activation of the immune system.  Inflammation is essential to removing debris and protecting the host from microbial invasion until barrier integrity is restored.  Bidirectional signaling between the neuroepithelium and immune cells regulates reparative inflammation and maintains homeostasis.  Pathologically persistent olfactory inflammation, such as in the setting of chronic rhinosinusitis, is associated with loss of mature olfactory neurons and failure of normal regeneration.  This dysfunctional state is mediated in part by basal cells, which participate in the immune response at the expense of their neuroepithelial progenitor function.  Re-establishment of the non-neuronal epithelial envelope and resolution of inflammation is a prerequisite to complete regeneration of a functional olfactory neuronal organ. Strategies to reverse the loss of the sense of smell due to age or disease will likely need to factor in neuro-immune pathways and/or leverage reparative inflammation to fully activate olfactory regeneration.

The Sinonasal Microbiome And The Sense Of Smell
Vijay R. Ramakrishnan
University of Colorado, Aurora, CO, United States

Recent years have seen a remarkable amount of research into the role of the microbiome in regulating mucosal homeostasis and inflammation. The nasal cavity and paranasal sinuses are colonized by dense assemblages of bacteria and other microbes in health and disease states. Microbiota signatures are associated with sinonasal health and disease, tissue inflammation, and symptom measures. In this symposium we will discuss rationale and hypotheses for olfactory dysfunction resulting from dysregulated microbiota-epithelial crosstalk in respiratory and olfactory epithelia. We will discuss recent publications in this area, and present novel findings from an ongoing human study. Finally, we will discuss challenges and limitations that are important to overcome in the next phase of research. 

9:00 - 11:00 AMParallel Room 2
Industry Symposium

12:00 - 2:00 PMPlenary Room 1
Oral Abstract Session #5

2:30 - 4:30 PMPlenary Room 1
Oral Abstract Session #6

5:00 - 7:00 PMPlenary Room 1
Awards Lectures 2021