Odor Stimuli Research Articles

Initial Characterization of a Subpopulation of Inherent Oscillatory Mammalian Olfactory Receptor Neurons.

Published evidence suggests that inherent rhythmically active or "bursting" primary olfactory receptor neurons (bORNs) in crustaceans have the previously undescribed functional property of encoding olfactory information by having their rhythmicity entrained by the odor stimulus. In order to determine whether such bORN-based encoding is a fundamental feature of olfaction that extends beyond crustaceans, we patch-clamped bORN-like ORNs in mice, characterized their dynamic properties, and show they align with the dynamic properties of lobster bORNs. We then characterized bORN-like activity by imaging the olfactory epithelium of OMP-GCaMP6f mice. Next, we showed rhythmic activity is not dependent upon the endogenous OR by patching ORNs in OR/GFP mice. Lastly, we showed the properties of bORN-like ORNs characterized in mice generalize to rats. Our findings suggest encoding odor time should be viewed as a fundamental feature of olfaction with the potential to be used to navigate odor plumes in animals as diverse as crustaceans and mammals.

Clinical validation of the olfactory detection threshold module of the Snap & Sniff® olfactory test system.

Quantitative olfactory testing is essential to determine the validity and nature of a patient's complaint, accurately monitor changes in function over time (including influences of pharmacological, surgical, or immunological interventions), detect malingering, and establish disability compensation. This work describes the clinical validation of an advanced rapid odor detection threshold test that standardizes odorant delivery and eliminates unsanitary sniff bottles, the need for blindfolds, and the possibility of touching an odorant stimulus to the nose. Snap & Sniff® single-staircase phenyl ethyl alcohol detection thresholds (S&S-Ts) were assessed bilaterally in 736 patients with chemosensory complaints; 421 received both bilateral and unilateral testing. The results were correlated with scores from the University of Pennsylvania Smell Identification Test (UPSIT) and the Smell Threshold Test (STT), a widely-used standardized threshold test. Test-retest reliability data were obtained for 50 patients. S&S-Ts were highly reliable (Spearman r = 0.84), correlated with the other olfactory test measures (rs > 0.65, ps < 0.0001), and required significantly shorter administration times than the STT (<10 minutes). Bilateral thresholds were systematically lower than unilateral thresholds, a phenomenon independent of presentation order but dependent upon the better functioning side of the nose. The S&S-Ts were sensitive to age and sex. No systematic left:right nasal side threshold differences were evident. The present study validates the use of Snap & Sniff® technology in the clinic setting. High test-retest reliability and brief administration times were evident. The S&S-T test allows for a reliable, valid, inexpensive, and rapid clinical means for quantitatively assessing human olfactory sensitivity.

Short or long runs: An exploratory study of odor-induced fMRI design.

Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique widely used in olfactory research. During a typical fMRI olfactory block-design, one functional "run" refers to a combination of multiple blocks with continuous brain image acquisition. The current study investigated the length of functional runs on odor-induced brain response signals (blood oxygen level dependent [BLOD]) within the primary and key secondary olfactory areas. Twenty-five female adults (age range 19 to 30 years, mean age 25 years) underwent a block-design fMRI measurement with odor stimulation. Twelve participants received the odor stimuli within a short run paradigm (six blocks in each 4-minute run, eight runs in total), and 13 participants received the odor stimulation with a long-run paradigm (12 blocks in each 8-minute run, four runs in total). For each paradigm, two odors (peach and rose) were alternatingly presented between runs. Participants rated odor intensity and pleasantness at the end of each run. Ratings and fMRI data were analyzed for different subsections and compared between groups. There was a higher level of brain activation in the insula and orbitofrontal cortex during the short-run paradigm as compared to the long-run paradigm. However, there was no difference for odor intensity or pleasantness ratings. The current study suggested the employment of short runs with multiple repetitions for odor stimulation during fMRI research. 3 Laryngoscope, 130:1110-1115, 2020.

Odor coding in the antenna of the tsetse fly Glossina morsitans

Tsetse flies transmit trypanosomiasis to humans and livestock across much of sub-Saharan Africa. Tsetse are attracted by olfactory cues emanating from their hosts. However, remarkably little is known about the cellular basis of olfaction in tsetse. We have carried out a systematic physiological analysis of the Glossina morsitans antenna. We identify 7 functional classes of olfactory sensilla that respond to human or animal odorants, CO2, sex and alarm pheromones, or other odorants known to attract or repel tsetse. Sensilla differ in their response spectra, show both excitatory and inhibitory responses, and exhibit different response dynamics to different odor stimuli. We find striking differences between the functional organization of the tsetse fly antenna and that of the fruit fly Drosophila melanogaster One morphological type of sensilla has a different function in the 2 species: Trichoid sensilla respond to pheromones in Drosophila but respond to a wide diversity of compounds in G. morsitans. In contrast to Drosophila, all tested G. morsitans sensilla that show excitatory responses are excited by one odorant, 1-octen-3-ol, which is contained in host emanations. The response profiles of some classes of sensilla are distinct but strongly correlated, unlike the organization described in the Drosophila antenna. Taken together, this study defines elements that likely mediate the attraction of tsetse to its hosts and that might be manipulated as a means of controlling the fly and the diseases it transmits.

Odor-related brain hyper-reactivity in euthymic bipolar disorder: An fMRI and ERP study

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the “Sniffin’ Sticks” olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

Slow presynaptic mechanisms that mediate adaptation in the olfactory pathway of Drosophila

The olfactory system encodes odor stimuli as combinatorial activity of populations of neurons whose response depends on stimulus history. How and on which timescales previous stimuli affect these combinatorial representations remains unclear. We use in vivo optical imaging in Drosophila to analyze sensory adaptation at the first synaptic step along the olfactory pathway. We show that calcium signals in the axon terminals of olfactory receptor neurons (ORNs) do not follow the same adaptive properties as the firing activity measured at the antenna. While ORNs calcium responses are sustained on long timescales, calcium signals in the postsynaptic projection neurons (PNs) adapt within tens of seconds. We propose that this slow component of the postsynaptic response is mediated by a slow presynaptic depression of vesicle release and enables the combinatorial population activity of PNs to adjust to the mean and variance of fluctuating odor stimuli.

Continuous Theta Burst Stimulation Over the Right Orbitofrontal Cortex Impairs Conscious Olfactory Perception

The right orbitofrontal cortex (rOFC) has been proposed as the region where conscious olfactory perception arises; however, evidence supporting this hypothesis has all been collected from neuroimaging and lesion studies in which only correlation and not a temporal pattern can be established. Continuous theta burst stimulation (cTBS) causes a reversible disruption of cortical activity and has been used successfully to disrupt orbitofrontal activity. To overcome intrinsic limitations of current experimental research, a crossover, double-blind, prospective and longitudinal study was carried out in which cTBS was applied over the rOFC to evaluate its effect on odorant stimuli detection. All subjects received real and sham cTBS. Experimental procedures were done in two different sessions with a separation of at least one week between them to avoid carryover and learning effects. A total of 15 subjects completed the experiment, and their data were included in the final analysis (10 women, 5 men, mean age 22.40 ± 3.41). Every session consisted of two different measures of the conscious olfactory perception task: A baseline measure and one 5 min after cTBS/sham. Compared to baseline, marks in the olfactory task during the sham cTBS session increased (p = 0.010), while marks during the real cTBS session decreased (p = 0.017). Our results support the hypothesis that rOFC is an important node of a complex network required for conscious olfactory perception to arise. However, the exact mechanism that explains our results is unclear and could be explained by the disruption of other cognitive functions related to the rOFC.

What do we know about the sensory drivers of emotions in foods and beverages?

In the past decade, while interest in emotions has markedly grown, the relationships between sensory properties and emotions, and particularly the role played by product liking/disliking, remain underexplored. In this review we provide a concise summary of recent research on the emotions elicited by unbranded foods and beverages, as well as simpler taste and odour stimuli. Scientific advances and research limitations will be discussed, while taking account of heterogeneity in results due to the different methodologies used in the field and the role of individual differences. Food scientists will benefit from this state-of-affairs review to drive advances in applied research regarding the sensory drivers of emotions, much in the same way past research has contributed to an understanding of the sensory drivers of liking.

Analysis of the role of wind information for efficient chemical plume tracing based on optogenetic silkworm moth behavior

Many animals use olfactory information to search for feeding areas and other individuals in real time and with high efficiency. We focus on the chemical plume tracing (CPT) ability of male silkworm moths and investigate an efficient CPT strategy for an autonomous robot. In the case of flying insects, the wind direction is an important factor in CPT, because the wind carries odors amongst other environmental information. However, whether the same phenomenon occurs in the walking silkworm moth has not been investigated. Therefore, we examine how the silkworm moth uses wind information during CPT. To accurately investigate the response to the wind direction, we introduce an optogenetic approach that replaces the odor stimulation with light stimulation, allowing us to separate the ‘wind stimulus’ from the ‘odor stimulus’. We examine how the moth uses wind direction information in a biological experiment, and find that the movement speed is significantly reduced when the wind speed is relatively fast (1.0 m s−1). By implementing this phenomenon in an autonomous robot, we can improve the successful search rate over that of the conventional moth-inspired algorithm. Regarding the search time, the proposed algorithm finds the odor source faster in a low-frequency odorant emission environment, whereas the search is slower than the conventional method when the odor frequency is higher. Therefore, switching from the use of wind direction information to odor information according to the frequency with which the odor is encountered leads to efficient CPT performance.

Using synthetic semiochemicals to train canines to detect bark beetle\u2013infested trees

Key messageThe dog detection allows timely removal by sanitation logging of first beetle-attacked trees before offspring emergence, preventing local beetle increases. Detection dogs rapidly learned responding to synthetic bark beetle pheromone components, with known chemical titres, allowing search training during winter in laboratory and field. Dogs trained on synthetics detected naturally attacked trees in summer at a distance of > 100 m.ContextAn early detection of first beetle-attacked trees would allow timely sanitation felling before offspring emergence, curbing local beetle increase.AimsWe tested if detection dogs, trained off-season on synthetic pheromone components from Ips typographus, could locate naturally bark beetle–infested spruce trees.MethodsIndoor training allowed dogs to discriminate between the infestation odours (target) and natural odours (non-target) from the forest. Odour stimuli were shown by chemical analysis to be bioactive at extremely low-levels released (< 10−4 ng/15 min) in the laboratory.ResultsDetection dogs, trained to recognise four different synthetic pheromone compounds in the wintertime, were able to detect naturally infested spruce trees unknown to humans the following summer. The dog-handler pairs were able to detect an infested spruce tree from the first hours of beetle attack until several weeks after first attack, long before discolouration of the crown. Trained sniffer dogs detected infested spruce trees out to ≥ 100 m, as measured by GPS-collar tracks.ConclusionDog-handler pairs appear to be more efficient than humans alone in timely detecting bark beetle infestations due to the canine’s ability to cover a greater area and detect by olfaction infestations from a far longer distance than can humans.

Structural and Functional Abnormalities in the Olfactory System of Fragile X Syndrome Models.

Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability. It is produced by mutation of the Fmr1 gene that encodes for the Fragile Mental Retardation Protein (FMRP), an important RNA-binding protein that regulates the expression of multiple proteins located in neuronal synapses. Individuals with FXS exhibit abnormal sensory information processing frequently leading to hypersensitivity across sensory modalities and consequently a wide array of behavioral symptoms. Insects and mammals engage primarily their sense of smell to create proper representations of the external world and guide adequate decision-making processes. This feature in combination with the exquisitely organized neuronal circuits found throughout the olfactory system (OS) and the wide expression of FMRP in brain regions that process olfactory information makes it an ideal model to study sensory alterations in FXS models. In the last decade several groups have taken advantage of these features and have used the OS of fruit fly and rodents to understand neuronal alteration giving rise to sensory perception issues. In this review article, we will discuss molecular, morphological and physiological aspects of the olfactory information processing in FXS models. We will highlight the decreased inhibitory/excitatory synaptic balance and the diminished synaptic plasticity found in this system resulting in behavioral alteration of individuals in the presence of odorant stimuli.

Classical conditioning in earthworms employing an odorous conditioned stimulus

The study of associative learning in invertebrates has become an essential tool for exploring their cognitive abilities and for studying the biological bases of learning and memory. In this experiment with earthworms, we paired a rose odour conditioned stimulus (CS) with a bright light unconditioned stimulus (US). After these pairings, the head retraction response — which is initially elicited by the bright light — is eventually evoked by the rose odour. This is the first demonstration of classical conditioning of an odour in earthworms (vibrations are usually employed as CSs), using a procedure that enables us to rule out an explanation in terms of pseudoconditioning.

Investigation of test performance of the dual reminder A-Not A (DR A-Not A) in comparison to 3-AFC for discriminating samples of drinking water

Although the relative performance of sensory discrimination methods is well theorized in Thurstonian modeling and signal detection theory (SDT), empirical research is needed to investigate how such theorized models could be validated in complex sensory testing situations of food and beverages. This paper presents a practical procedure to utilize the existing SDT-based A-Not A sensory discrimination model based on a beta-strategy for detecting the off-sensory quality of samples of drinking water and validates the model for effective and efficient sensory quality management of food and beverages. Dual reminder A-Not A (DR A-Not A) using two tastings of the reference stimulus before evaluating every test stimulus is proposed as the optimal test procedure because it uses more sensitive test sequences and facilitates subjects’ familiarization with the standard quality of the reference. To test the performance of DR A-Not A, 3-AFC, which also uses three stimuli and is the recommended method for detecting odor or taste stimuli by ASTM, was used as a control method. In Experiment 1, 98 subjects each performed both DR A-Not A and 3-AFC. Based on these results, only sensitive subjects were selected for the next experiment, in which they were divided into two equally well performing groups. In Experiment 2, each group performed either DR A-Not A or 3-AFC over three repeated sessions. The results confirmed that the A-Not A beta-strategy was adopted for DR A-Not A and that its test performance was improved over replications. These results suggest that although DR A-Not A is an unspecified difference test method and does not use a forced-choice task, embedding the familiarization procedure for the reference renders it an effective sensory difference method for the sensory quality management of drinking water.

Reciprocal Inhibitory Glomerular Circuits Contribute to Excitation-Inhibition Balance in the Mouse Olfactory Bulb.

The major inhibitory interneurons in olfactory bulb (OB) glomeruli are periglomerular cells (PGCs) and short axon cells (SACs). PGCs and SACs provide feedforward inhibition to all classes of projection neurons, but inhibition between PGCs and SACs is not well understood. We crossed Cre and GFP transgenic mice and used virally-delivered optogenetic constructs to selectively activate either SACs or GAD65cre-ChR2-positive PGCs while recording from identified GAD65cre-ChR2-positive PGCs or SACs, respectively, to investigate inhibitory interactions between these two interneuron types. We show that GAD65cre-ChR2-positive PGCs robustly inhibit SACs and SACs strongly inhibit PGCs. SACs form the interglomerular circuit, which inhibits PGCs in distant glomeruli. Activation of GAD65cre-ChR2-positive PGCs monosynaptically inhibit mitral cells (MCs), which complements recent findings that SACs directly inhibit MCs. Thus, both classes of glomerular inhibitory neurons inhibit each other, as well as OB output neurons. We further show that olfactory nerve input to one glomerulus engages the interglomerular circuit and inhibits PGCs in distant glomeruli. Sensory activation of the interglomerular circuit directly inhibits output neurons in other glomeruli and by inhibiting intraglomerular PGCs, may potentially disinhibit output neurons in other glomeruli. The nature and context of odorant stimuli may determine whether inhibition or excitation prevails so that odors are represented in part by patterns of active and inactive glomeruli.

Grid-like Neural Representations Support Olfactory Navigation of a Two-Dimensional Odor Space

Searching for food, friends, and mates often begins with an airborne scent. Importantly, odor concentration rises with physical proximity to an odorous source, suggesting a framework for orienting within olfactory landscapes to optimize behavior. Here, we created a two-dimensional odor space composed purely of odor stimuli to model how a navigator encounters smells in a natural environment. We show that human subjects can learn to navigate in olfactory space and form predictions of to-be-encountered smells. During navigation, fMRI responses in entorhinal cortex and ventromedial prefrontal cortex take the form of grid-like representations with hexagonal periodicity and entorhinal grid strength scaled with behavioral performance across subjects. The identification of olfactory grid-like codes with 6-fold symmetry highlights a unique neural mechanism by which odor information can be assembled into spatially navigable cognitive maps, optimizing orientation, and path finding toward an odor source.

Olfactory Event-Related Potentials and Exhaled Organic Volatile Compounds: The Slow Link Between Olfactory Perception and Breath Metabolic Response. A Pilot Study on Phenylethyl Alcohol and Vaseline Oil.

Olfactory processing starts with the breath and elicits neuronal, metabolic and cortical responses. This process can be investigated centrally via the Olfactory Event-Related Potentials (OERPs) and peripherally via exhaled Volatile Organic Compounds (VOCs). Despite this, the relationship between OERPs (i.e., N1 and Late Positive Component LPC) and exhaled VOCs has not been investigated enough. The aim of this research is to study OERPs and VOCs connection to two different stimuli: phenylethyl alcohol (PEA) and Vaseline Oil (VO). Fifteen healthy subjects performed a perceptual olfactory task with PEA as a smell target stimulus and VO as a neutral stimulus. The results suggest that OERPs and VOCs distributions follow the same amplitude trend and that PEA is highly arousing in both psychophysiological measures. PEA shows ampler and faster N1, a component related to the sensorial aspect of the stimulus. The N1 topographic localization is different between PEA and VO: PEA stimulus evokes greater N1 in the left centroparietal site. LPC, a component elicited by the perceptual characteristic of the stimulus, shows faster latency in the Frontal lobe and decreased amplitude in the Central and Parietal lobe elicited by the PEA smell. Moreover, the delayed time between the onset of N1-LPC and the onset of VOCs seems to be about 3 s. This delay could be identified as the internal metabolic time in which the odorous stimulus, once perceived at the cortical level, is metabolized and subsequently exhaled. Furthermore, the VO stimulus does not allocate the attentive, perceptive and metabolic resource as with PEA.

The power of odour volatiles from unifloral melipona honey evaluated by gas chromatography-olfactometry Osme techniques.

The quality and power of each odorous volatile present in the headspace of unifloral honey velame branco (Croton heliotropiifolius Kunth) prepared by stingless uruçu (Melipona scutellaris Latrelle) were evaluated using the gas chromatography-olfactometry Osme technique. Five trained panellists evaluated the sensory chromatographic effluent in three replications, and the results were integrated by SCDTI software. Of the 42 compounds identified in the chromatogram, 17 odorous stimuli were detected by the sensory panel. Among these compounds, the most odoriferous impacts were pentanoate acetate 'ripe fruit', safranal green, medicinal plant and methyl eugenol 'clove, tea'. The furaneol compounds, hotrienol and benzaldehyde showed aroma notes associated with honey. These results are important since, in addition to revealing the presence of compounds that are not identified by other analytical methods, they can also assist in the verification of monofloral honeys compliance. © 2019 Society of Chemical Industry.

Acute exposure to diesel exhaust induces central nervous system stress and altered learning and memory in honey bees

For effective foraging, many insect pollinators rely on the ability to learn and recall floral odours, behaviours that are associated with a complex suite of cellular processes. Here, we investigated how acute exposure to a high-dose of diesel exhaust (containing 19.8 and 17.5 ppm of NO and NO2, respectively) affected associative learning behaviour of honey bees (Apis mellifera) and expression of a ubiquitous heat shock protein, HSP70, in their central nervous system (CNS). To determine whether exposure to diesel exhaust would alter their tolerance to a subsequent abiotic stress, we further subjected individuals to heat stress. Diesel exhaust exposure decreased honey bees’ ability to learn and recall a conditioned odour stimulus. Whilst there was no significant difference in CNS HSP70 expression between honey bees exposed to either diesel exhaust or clean air across the entire duration of the experiment (3.5 h), there was a significant effect of time and a significant interaction between exposure treatment and time. This interaction was investigated using correlation analyses, which demonstrated that only in the diesel exhaust exposed honey bees was there a significant positive correlation between HSP70 expression and time. Furthermore, there was a 44% reduction in honey bee individuals that were able to recall the odour 72 h after diesel exposure compared with clean air control individuals. Moreover, diesel exhaust affected A. mellifera in a way that reduced their ability to survive a second subsequent stressor. Such negative effects of air pollution on learning, recall, and stress tolerance has potential to reduce foraging efficiency and pollination success of individual honey bees.

The effect of odor exposure time on olfactory cognitive processing: An ERP study.

The present study aimed to investigate the effects of stimulus time duration on central nervous odor processing. Twenty-one young healthy males participate in our study. There are three odor mixtures in this study and every odor mixture has two different duration time (300 ms; 500 ms). The odor was presented via a computer - controlled olfactometer and EEG was recorded from 64 scalp locations. At behavioral level, the longer the odor stimulus was presented, the greater the concentration was perceived by participants. Electrophysiological data showed that longer duration time lengthened the latency of Negative waves of about 200 ms appeared in stimulation (N2) and Positive waves of about 300 ms appeared in stimulation (P3) components, besides, have a larger N2 amplitude than the shorter duration time condition in the mid-frontal and left frontal-temporal areas. These results revealed that duration time of odor mixture do have an influence on the central nervous odor processing.

Activity-Dependent Remodeling of Drosophila Olfactory Sensory Neuron Brain Innervation during an Early-Life Critical Period.

Critical periods are windows of development when the environment has a pronounced effect on brain circuitry. Models of neurodevelopmental disorders, including autism spectrum disorders, intellectual disabilities, and schizophrenia, are linked to disruption of critical period remodeling. Critical periods open with the onset of sensory experience; however, it remains unclear exactly how sensory input modifies brain circuits. Here, we examine olfactory sensory neuron (OSN) innervation of the Drosophila antennal lobe of both sexes as a genetic model of this question. We find that olfactory sensory experience during an early-use critical period drives loss of OSN innervation of antennal lobe glomeruli and subsequent axon retraction in a dose-dependent mechanism. This remodeling does not result from olfactory receptor loss or OSN degeneration, but rather from rapid synapse elimination and axon pruning in the target olfactory glomerulus. Removal of the odorant stimulus only during the critical period leads to OSN reinnervation, demonstrating that remodeling is transiently reversible. We find that this synaptic refinement requires the OSN-specific olfactory receptor and downstream activity. Conversely, blocking OSN synaptic output elevates glomeruli remodeling. We find that GABAergic neurotransmission has no detectable role, but that glutamatergic signaling via NMDA receptors is required for OSN synaptic refinement. Together, these results demonstrate that OSN inputs into the brain manifest robust, experience-dependent remodeling during an early-life critical period, which requires olfactory reception, OSN activity, and NMDA receptor signaling. This work reveals a pathway linking initial olfactory sensory experience to glutamatergic neurotransmission in the activity-dependent remodeling of brain neural circuitry in an early-use critical period.SIGNIFICANCE STATEMENT Neurodevelopmental disorders manifest symptoms at specific developmental milestones that suggest an intersection between early sensory experience and brain neural circuit remodeling. One classic example is Fragile X syndrome caused by loss of an RNA-binding translation regulator of activity-dependent synaptic refinement. As a model, Drosophila olfactory circuitry is well characterized, genetically tractable, and rapidly developing, and thus ideally suited to probe underlying mechanisms. Here, we find olfactory sensory neurons are dramatically remodeled by heightened sensory experience during an early-life critical period. We demonstrate removing the olfactory stimulus during the critical period can reverse the connectivity changes. We find that this remodeling requires neural activity and NMDA receptor-mediated glutamatergic transmission. This improved understanding may help us design treatments for neurodevelopmental disorders.