Alterations in odor hedonics in the 5XFAD Alzheimer’s disease mouse model and the influence of sex

Olfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics are reported in the early stages of Alzheimer’s disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination – recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-months old 5XFAD (Tg6799) mice in the five-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD mice investigated odors longer than controls, an effect that was driven by 6-months old mice. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed towards individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences towards some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD mice. Taken together, 5XFAD mice, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations which may occur in AD mouse models, and how these are influenced by biological sex.

Variability in Retronasal Odor Identification Among Patients With Chronic Rhinosinusitis

Background Retronasal olfaction is important in flavor detection and enjoyment. The ability to identify specific individual retronasal odors may play a role in quality of life for patients with chronic rhinosinusitis (CRS). Objective To identify patterns and improve understanding of retronasal identification of individual odors in CRS patients. Methods Patients diagnosed with CRS underwent retronasal and orthonasal (Sniffin’ Sticks) olfactory testing and taste testing (taste strips). Retronasal identification was tested with presentation of flavored powders on the posterior tongue. Retronasal identification for individual odors was compared with results of orthonasal and taste testing. Results Seventy participants were evaluated. Retronasal identification correlated with orthonasal identification and discrimination for most individual odors. Among all patients, cinnamon and apple were identified better retronasally and banana better orthonasally ( P < .05). Anosmics identified retronasal orange, cinnamon, mushroom, coffee, smoked ham, peach, ginger, grape, and cheese more than would be expected by chance for a forced-choice paradigm with 3 distractor items ( P < .05), and this was independent of objective taste function for most odors. Conclusion Retronasal and orthonasal identification of most odors correlate in CRS patients; however, patients with anosmia can still identify certain retronasal odors more often than expected. These odors do not appear to stimulate gustatory pathways and may involve trigeminal stimulation. Understanding preserved retronasal neural stimuli may allow providers to improve eating-related quality of life in these patients.

An odor delivery system for arbitrary time-varying patterns of odors, mixtures and concentrations

Odor stimuli in the natural environment are intermittent and the concentration of any given odor fluctuates rapidly over time. Further, even in the simplest scenario, the olfactory sensors receive uncorrelated, intermittent inputs in the form of odor plumes arising from several odor sources in the local environment. However, typically used odor stimuli under laboratory settings are restricted to long-duration (~seconds), single pulse of one odor at a time that are rarely encountered in nature. This inadequate choice of odor stimuli is due to the dearth of affordable odor delivery systems that can generate plume-like, naturalistic stimuli with high reproducibility such as to allow for repeat measurements under laboratory conditions. We thus developed an odor delivery system that generates arbitrary time-varying patterns of individual odors and ternary mixtures at time scales of ~20 Hz. Here, we provide a detailed description of the construction and output characterization of our odor delivery system.

Expanding the olfactory code by in silico decoding of odor-receptor chemical space

Coding of information in the peripheral olfactory system depends on two fundamental factors: interaction of individual odors with subsets of the odorant receptor repertoire and mode of signaling that an individual receptor-odor interaction elicits, activation or inhibition. We develop a cheminformatics pipeline that predicts receptor–odorant interactions from a large collection of chemical structures (>240,000) for receptors that have been tested to a smaller panel of odorants (∼100). Using a computational approach, we first identify shared structural features from known ligands of individual receptors. We then use these features to screen in silico new candidate ligands from >240,000 potential volatiles for several Odorant receptors (Ors) in the Drosophila antenna. Functional experiments from 9 Ors support a high success rate (∼71%) for the screen, resulting in identification of numerous new activators and inhibitors. Such computational prediction of receptor–odor interactions has the potential to enable systems level analysis of olfactory receptor repertoires in organisms.