Low Odor Concentrations Research Articles

Circuit Contributions to Sensory-Driven Glutamatergic Drive of Olfactory Bulb Mitral and Tufted Cells During Odorant Inhalation.

In the mammalian olfactory bulb (OB), mitral/tufted (MT) cells respond to odorant inhalation with diverse temporal patterns that are thought to encode odor information. Much of this diversity is already apparent at the level of glutamatergic input to MT cells, which receive direct, monosynaptic excitatory input from olfactory sensory neurons (OSNs) as well as a multisynaptic excitatory drive via glutamatergic interneurons. Both pathways are also subject to modulation by inhibitory circuits in the glomerular layer of the OB. To understand the role of direct OSN input vs. postsynaptic OB circuit mechanisms in shaping diverse dynamics of glutamatergic drive to MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized mice while blocking multisynaptic excitatory drive with ionotropic glutamate receptor antagonists and blocking presynaptic modulation of glutamate release from OSNs with GABAB receptor antagonists. GABAB receptor blockade increased the magnitude of inhalation-linked glutamate transients onto MT cell apical dendrites without altering their inhalation-linked dynamics, confirming that presynaptic inhibition impacts the gain of OSN inputs to the OB. Surprisingly, blockade of multisynaptic excitation only modestly impacted glutamatergic input to MT cells, causing a slight reduction in the amplitude of inhalation-linked glutamate transients in response to low odorant concentrations and no change in the dynamics of each transient. The postsynaptic blockade also modestly impacted glutamate dynamics over a slower timescale, mainly by reducing adaptation of the glutamate response across multiple inhalations of odorant. These results suggest that direct glutamatergic input from OSNs provides the bulk of excitatory drive to MT cells, and that diversity in the dynamics of this input may be a primary determinant of the temporal diversity in MT cell responses that underlies odor representations at this stage.

Analysis of Separation Distances under Varying Odour Emission Rates and Meteorology: A WWTP Case Study

A wide variability of odour impact criteria is found around the world. The objective of this research work was to evaluate the influence of the uncertainties related to some individual stages of odour impact assessment in the application of regulatory criteria. The evaluation procedure was established by following the guidelines of the Northern Italian regions. A wastewater treatment plant located in Northern Italy was considered as a case study. Odour dispersion modelling was carried out with the CALPUFF model. The study focused on two phases of the assessment. The first phase was the selection of the meteorology datasets. For low odour concentration thresholds (CT = 1 OU m−3), the results showed that two different years (2018 and 2019) provided similar patterns of the separation distances. The difference between the two years tended to increase by increasing the value of the concentration threshold (CT = 3 OU m−3 and CT = 5 OU m−3). The second phase of the assessment was the selection of the open field correction method for wind velocity used in the calculation of odour emission rates (OERs). Three different relationships were considered: the power law, the logarithmic law and the Deaves–Harris (D–H) law. The results showed that OERs and separation distances varied depending on the selected method. Taking the power law as the reference, the average variability of the separation distances was between −7% (D–H law) and +10% (logarithmic law). Higher variability (up to 25%) was found for single transport distances. The present study provides knowledge towards a better alignment of the concept of the odour impact criteria.

Differential Role for a Defined Lateral Horn Neuron Subset in Na\xefve Odor Valence in Drosophila

Value coding of external stimuli in general, and odor valence in particular, is crucial for survival. In flies, odor valence is thought to be coded by two types of neurons: mushroom body output neurons (MBONs) and lateral horn (LH) neurons. MBONs are classified as neurons that promote either attraction or aversion, but not both, and they are dynamically activated by upstream neurons. This dynamic activation updates the valence values. In contrast, LH neurons receive scaled, but non-dynamic, input from their upstream neurons. It remains unclear how such a non-dynamic system generates differential valence values. Recently, PD2a1/b1 LH neurons were demonstrated to promote approach behavior at low odor concentration in starved flies. Here, we demonstrate that at high odor concentrations, these same neurons contribute to avoidance in satiated flies. The contribution of PD2a1/b1 LH neurons to aversion is context dependent. It is diminished in starved flies, although PD2a1/b1 neural activity remains unchanged, and at lower odor concentration. In addition, PD2a1/b1 aversive effect develops over time. Thus, our results indicate that, even though PD2a1/b1 LH neurons transmit hard-wired output, their effect on valence can change. Taken together, we suggest that the valence model described for MBONs does not hold for LH neurons.

Possible Stochastic Mechanism for Improving the Selectivity of Olfactory Projection Neurons

A mechanism is proposed for increasing selectivity of olfactory bulb projection neurons as compared to the olfactory receptor neurons, which could operate under low odor concentration, when the lateral inhibition mechanism becomes inefficient. The mechanism proposed is based on the threshold-type reaction to stimuli a projection neuron receives from the receptor neurons, the stochastic nature of those stimuli and electrical leakage in the projection neurons. The mechanism operates at the level of individual projection neuron and does not require involvement of other bulbar neurons. Keywords: olfactory receptor neuron; projection neuron; selectivity; stochastic process; theory

Tests of the chromatographic theory of olfaction with highly soluble odors: a combined electro-olfactogram and computational fluid dynamics study in the mouse.

ABSTRACTThe idea that the vertebrate nasal cavity operates like a gas chromatograph to separate and discriminate odors, referred to herein as the ‘chromatographic theory’ (CT), has a long and interesting history. Though the last decade has seen renewed interest in the notion, its validity remains in question. Here we examine a necessary condition of the theory: a correlation between nasal odor deposition patterns based on mucus solubility and the distribution of olfactory sensory neuron odotypes. Our recent work in the mouse failed to find such a relationship even across large sorption gradients within the olfactory epithelium (OE). However, these studies did not test extremely soluble odorants or low odor concentrations, factors that could explain our inability to find supporting evidence for the CT. The current study combined computational fluid dynamics (CFD) simulations of odor sorption patterns and electro-olfactogram (EOG) measurements of olfactory sensory neuron responses. The odorants tested were at the extremes of mucus solubility and at a range of concentrations. Results showed no relationship between local odor sorption patterns and EOG response maps. Together, results again failed to support a necessary condition of the CT casting further doubt on the viability of this classical odor coding mechanism.

History-Dependent Odor Processing in the Mouse Olfactory Bulb.

In nature, animals normally perceive sensory information on top of backgrounds. Thus, the neural substrate to perceive under background conditions is inherent in all sensory systems. Where and how sensory systems process backgrounds is not fully understood. In olfaction, just a few studies have addressed the issue of odor coding on top of continuous odorous backgrounds. Here, we tested how background odors are encoded by mitral cells (MCs) in the olfactory bulb (OB) of male mice. Using in vivo two-photon calcium imaging, we studied how MCs responded to odors in isolation versus their responses to the same odors on top of continuous backgrounds. We show that MCs adapt to continuous odor presentation and that mixture responses are different when preceded by background. In a subset of odor combinations, this history-dependent processing was useful in helping to identify target odors over background. Other odorous backgrounds were highly dominant such that target odors were completely masked by their presence. Our data are consistent in both low and high odor concentrations and in anesthetized and awake mice. Thus, odor processing in the OB is strongly influenced by the recent history of activity, which could have a powerful impact on how odors are perceived.SIGNIFICANCE STATEMENT We examined a basic feature of sensory processing in the olfactory bulb. Specifically, we measured how mitral cells adapt to continuous background odors and how target odors are encoded on top of such background. Our results show clear differences in odor coding based on the immediate history of the stimulus. Our results support the argument that odor coding in the olfactory bulb depends on the recent history of the sensory environment.

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons.

Many animals follow odor trails to find food, nesting sites, or mates, and they require only faint olfactory cues to do so. The performance of a tracking dog, for instance, poses the question on how the animal is able to distinguish a target odor from the complex chemical background around the trail. Current concepts of odor perception suggest that animals memorize each odor as an olfactory object, a percept that enables fast recognition of the odor and the interpretation of its valence. An open question still is how this learning process operates efficiently at the low odor concentrations that typically prevail when animals inspect an odor trail. To understand olfactory processing under these conditions, we studied the role of an amplification mechanism that boosts signal transduction at low stimulus intensities, a process mediated by calcium‐gated anoctamin 2 chloride channels. Genetically altered Ano2 −/− mice, which lack these channels, display an impaired cue‐tracking behavior at low odor concentrations when challenged with an unfamiliar, but not with a familiar, odor. Moreover, recordings from the olfactory epithelium revealed that odor coding lacks sensitivity and temporal resolution in anoctamin 2‐deficient mice. Our results demonstrate that the detection of an unfamiliar, weak odor, as well as its memorization as an olfactory object, require signal amplification in olfactory receptor neurons. This process may contribute to the phenomenal tracking abilities of animals that follow odor trails.

Spontaneously active NaV1.5 sodium channels may underlie odor sensitivity.

The olfactory system is remarkably sensitive to airborne odor molecules, but precisely how very low odor concentrations bordering on just a few molecules per olfactory sensory neuron can trigger graded changes in firing is not clear. This report reexamines signaling in olfactory sensory neurons in light of the recent account of NaV1.5 sodium channel-mediated spontaneous firing. Using a model of spontaneous channel activity, the study shows how even submillivolt changes in membrane potential elicited by odor are expected to cause meaningful changes in NaV1.5-dependent firing. The results suggest that the random window currents of NaV1.5 channels may underpin not only spontaneous firing in olfactory sensory neurons but the cellular response to odor as well, thereby ensuring the robustness and sensitivity of signaling that is especially important for low odor concentrations.

Sex and Genotype Differences in Odor Detection in the 3×Tg-AD and 5XFAD Mouse Models of Alzheimer's Disease at 6 Months of Age.

Deficits in odor identification and detection are early symptoms of Alzheimer's disease (AD). Two transgenic mouse models of AD, the 5XFAD and the 3×Tg-AD mice and their wildtype controls, were assessed for olfactory detection with decreasing concentrations of ethyl acetate in a go no-go operant olfactometer task at 6 months of age. For both the 5XFAD and their B6SJLF1 wildtype littermates, females made fewer errors in detecting the ethyl acetate than males on all but the lowest odor concentrations. Female 5XFAD mice performed slightly better than their female wildtype littermates on the higher odor concentrations, though not at the lowest concentration. The 3×Tg-AD females showed decreased olfactory detection compared with their wildtype B6129S1 controls, whereas there was no difference in the males. Therefore, although the 5XFAD mice showed no olfactory detection deficits, female 3×Tg-AD mice had impaired olfactory detection at low odor concentrations but males did not. This difference in odor detection should be considered in studies of olfactory learning and memory, as differences in performance may be due to sensory rather than cognitive factors, though detection seems unimpaired at high odor concentrations.

A Circuit for Gradient Climbing in C. elegans Chemotaxis.

Animals have a remarkable ability to track dynamic sensory information. For example, the nematode Caenorhabditis elegans can locate a diacetyl odor source across a 100,000-fold concentration range. Here, we relate neuronal properties, circuit implementation, and behavioral strategies underlying this robust navigation. Diacetyl responses in AWA olfactory neurons are concentration and history dependent; AWA integrates over time at low odor concentrations, but as concentrations rise, it desensitizes rapidly through a process requiring cilia transport. After desensitization, AWA retains sensitivity to small odor increases. The downstream AIA interneuron amplifies weak odor inputs and desensitizes further, resulting in a stereotyped response to odor increases over three orders of magnitude. The AWA-AIA circuit drives asymmetric behavioral responses to odor increases that facilitate gradient climbing. The adaptation-based circuit motif embodied by AWA and AIA shares computational properties with bacterial chemotaxis and the vertebrate retina, each providing a solution for maintaining sensitivity across a dynamic range.

Computational modeling suggests distinct, location-specific function of norepinephrine in olfactory bulb and piriform cortex.

Noradrenergic modulation from the locus coerulus is often associated with the regulation of sensory signal-to-noise ratio. In the olfactory system, noradrenergic modulation affects both bulbar and cortical processing, and has been shown to modulate the detection of low concentration stimuli. We here implemented a computational model of the olfactory bulb and piriform cortex, based on known experimental results, to explore how noradrenergic modulation in the olfactory bulb and piriform cortex interact to regulate odor processing. We show that as predicted by behavioral experiments in our lab, norepinephrine can play a critical role in modulating the detection and associative learning of very low odor concentrations. Our simulations show that bulbar norepinephrine serves to pre-process odor representations to facilitate cortical learning, but not recall. We observe the typical non-uniform dose—response functions described for norepinephrine modulation and show that these are imposed mainly by bulbar, but not cortical processing.

Characterization of odor emission on the working face of landfill and establishing of odorous compounds index

Temporal variation (seasonal and daily) of odor emission on the working face of a large sanitary landfill in China was characterized through a 2 yearlong case study. Odor pollution was most serious in spring and autumn, while lower odor concentrations were detected in summer and winter. The daily fluctuation of odor concentration on the working face showed that 2:00am, 6:00am, 2:00pm and 10:00pm were the “most probable times” for odor pollution occurrence, which deserves focused attention in odor control projects. Correlations analysis found that 41% of the variance in odor concentrations can be explained by the chemical concentrations of odorous compounds.Moreover, the selection criteria for the index of odorous compounds were also established by evaluating the odor concentration, contribution to odor strength and the frequency of each compound present in all the samples. Ethyl alcohol, α-piene, hydrogen sulfide, dimethyl sulfide, limonene, methyl mercaptan, dimethyl disulfide, and diethyl sulfide comprise the index of odorous compounds on the working face of typical municipal solid waste landfill in China.

Application of PTR-MS for measuring odorant emissions from soil application of manure slurry.

Odorous volatile organic compounds (VOC) and hydrogen sulfide (H2S) are emitted together with ammonia (NH3) from manure slurry applied as a fertilizer, but little is known about the composition and temporal variation of the emissions. In this work, a laboratory method based on dynamic flux chambers packed with soil has been used to measure emissions from untreated pig slurry and slurry treated by solid-liquid separation and ozonation. Proton-transfer-reaction mass spectrometry (PTR-MS) was used to provide time resolved data for a range of VOC, NH3 and H2S. VOC included organic sulfur compounds, carboxylic acids, phenols, indoles, alcohols, ketones and aldehydes. H2S emission was remarkably observed to take place only in the initial minutes after slurry application, which is explained by its high partitioning into the air phase. Long-term odor effects are therefore assessed to be mainly due to other volatile compounds with low odor threshold values, such as 4-methylphenol. PTR-MS signal assignment was verified by comparison to a photo-acoustic analyzer (NH3) and to thermal desorption GC/MS (VOC). Due to initial rapid changes in odorant emissions and low concentrations of odorants, PTR-MS is assessed to be a very useful method for assessing odor following field application of slurry. The effects of treatments on odorant emissions are discussed.

National Odour Impact Criteria: Are the Modelled Separation Distances Between Sources and Receptors Comparable?

To determine separation distances between odour sources and residential areas (in order to safeguard against nuisance and complaints), odour impact criteria (OIC) are adopted by the national regulatory authorities. There is a wide variety of OIC used for this purpose, which differ by the odour concentration threshold (between 0.12 ou m-3 and 10 ou m-3), the averaging period (hourly or instantaneous) and by thetolerated exceedance probability of the adopted threshold (between 0.1% and about 35% of the time). Using two national OIC for the protection of rural residential properties (Ireland with a threshold of 6 ou m-3 and a tolerated exceedance probability of 2%) and Germany (with a threshold of 0.25 ou m-3 and a tolerated exceedance probability of 20%), the direction-dependent separation distances were calculated, and compared against those of 166 different OIC. It is interesting to investigate whether the large range ofnational OIC results in large differences in the modelled separation distances. For this investigation, the normalised mean standard error (NMSR) was selected as a statistical measure. There are two groups of OIC used in various jurisdictions: the first one with a low odour concentration threshold and a high tolerated exceedance probability (e.g. Germany); and the second group with a high odour concentration threshold and a low tolerated exceedance probability (e.g. Ireland). The modelled direction-dependent separation distances (using OIC which are supposed to offer the same protection level) can vary significantly. The OIC of the second group, considering higher ambient odour concentrations, show a much lower sensitivity to site-specific meteorological data. Therefore, a higher tolerated exceedance probability seems more appropriate for the determination of OIC. Even if the similarity of separation distances by various OIC could be determined, the direction-dependent separation distances differ considerably for the same protection level for a certain receptor type, e.g. rural residential properties.

Comparability of separation distances between odour sources and residential areas determined by various national odour impact criteria

To determine separation distances between odour sources and residential areas to avoid odour nuisance and complaints by the residents, odour impact criteria OIC have to be adopted by the responsible authorities. There is a wide variety of OIC used for this purpose, which differ by the odour concentration threshold between 0.12 ou m−3 and 10 ou m−3 and by the tolerated exceedance probability of this threshold between 0.1% and about 35%. For two national OIC for a protection level of rural residential areas (Ireland with a threshold of 6 ou m−3 and an exceedance probability of 2% and Germany 0.25 ou m−3/20%) and two national OIC fur urban residential areas (Ireland: 3 ou m−3/2%, Germany 0.25 ou m−3/13.6%), the direction depending separation distances were calculated, and the similarity to 166 various OIC was investigated. The large discrepancies among the national OIC provokes the question if separation distances calculated for the same protection level are then still comparable and thus meet general expectations or not. For this comparison the normalised mean standard error was selected as a statistical measure. There are two groups of OIC used in various jurisdictions: The first one with a low odour concentration threshold and a high exceedance probability evaluating ambient odour intensity close to the perception threshold (Germany) and the second group of the remaining countries with high odour intensity by using a high concentration threshold and a low exceedance probability. The direction depending separation distances of OIC with the same protection level can vary considerably. The OIC of the last group, evaluating higher ambient odour intensities, show a much lower sensitivity to site specific meteorological data. Therefore a higher exceedance probability seems more appropriate for the determination of OIC. Even if the similarity of separation distances by various OIC could be determined, the direction dependent separation distances differ considerably for the same protection level.

An information theoretic model of information processing in the Drosophila olfactory system: the role of inhibitory neurons for system efficiency

Fruit flies (Drosophila melanogaster) rely on their olfactory system to process environmental information. This information has to be transmitted without system-relevant loss by the olfactory system to deeper brain areas for learning. Here we study the role of several parameters of the fly's olfactory system and the environment and how they influence olfactory information transmission. We have designed an abstract model of the antennal lobe, the mushroom body and the inhibitory circuitry. Mutual information between the olfactory environment, simulated in terms of different odor concentrations, and a sub-population of intrinsic mushroom body neurons (Kenyon cells) was calculated to quantify the efficiency of information transmission. With this method we study, on the one hand, the effect of different connectivity rates between olfactory projection neurons and firing thresholds of Kenyon cells. On the other hand, we analyze the influence of inhibition on mutual information between environment and mushroom body. Our simulations show an expected linear relation between the connectivity rate between the antennal lobe and the mushroom body and firing threshold of the Kenyon cells to obtain maximum mutual information for both low and high odor concentrations. However, contradicting all-day experiences, high odor concentrations cause a drastic, and unrealistic, decrease in mutual information for all connectivity rates compared to low concentration. But when inhibition on the mushroom body is included, mutual information remains at high levels independent of other system parameters. This finding points to a pivotal role of inhibition in fly information processing without which the system efficiency will be substantially reduced.

Sniffing shapes the dynamics of olfactory bulb gamma oscillations in awake behaving rats

Mammals actively sample the environment for relevant olfactory objects. This active sampling is revealed by rapid changes in respiratory rate that influence the olfactory input. Yet the role of sniffing in shaping the neural responses to odorants has not been elucidated. In the olfactory bulb (OB), odorant-evoked gamma oscillations reflect the synchronous activity of mitral/tufted cells, a proposed mechanism for odorant representation. Here we examined the effect of sniffing frequency on the odorant-evoked gamma oscillations in the OB. We simultaneously recorded the respiratory rate and the local field potential while rats performed a lick/no-lick olfactory discrimination task with low odorant concentrations. High-frequency sniffing (HFS) augmented the power of gamma oscillations, suggesting an increase in the sensitivity to odorants. By contrast, coupling of the gamma oscillations to the sniff cycle and the amplitude of individual bursts were not modified by the respiratory rate. However, HFS prolonged the overall response to odorants and increased the frequency of the gamma oscillations, indicating that HFS reduces the adaptation to continuous odorant stimulation. Therefore, the increase in gamma power during HFS is the result of more frequent gamma bursts and the extended response to odorants. As odorant discrimination can be performed in a single sniff, a reduction in the adaptation mediated by HFS of novel odorants may facilitate odorant memory formation for subsequent odorant identification. Finally, these results corroborate that olfactory sampling should be integrated to the study of odorant coding in behaving animals.

Cellular & molecular Ca2+ microdomains in olfactory cilia support low signaling amplification of odor transduction

AbstractSignal transduction depends critically on the spatial localization of protein constituents. A key question in odor transduction is whether chemotransduction proteins organize into discrete molecular complexes throughout olfactory cilia or distribute homogeneously along the ciliary membrane. Our recordings of Ca2+ changes in individual cilia with unprecedented spatial and temporal resolution, by the use of two‐photon microscopy, provide solid evidence for Ca2+ microdomains (transducisomes). Dissociated frog olfactory neurons were preloaded with caged‐cAMP and fluo‐4 acetoxymethyl ester probe Ca2+ indicator. Ca2+ influx through cyclic nucleotide‐gated (CNG) channels was evoked by uniformly photoreleasing cAMP, while ciliary Ca2+ was measured. Discrete fluorescence events were clearly resolved. Events were missing in the absence of external Ca2+, consistent with the absence of internal Ca2+ sources. Fluorescence events at individual microdomains resembled single‐CNG channel fluctuations in shape, mean duration and kinetics, indicating that transducisomes typically contain one to three CNG channels. Inhibiting the Na+/Ca2+ exchanger or the Ca2+‐ATPase prolonged the decay of evoked intraciliary Ca2+ transients, supporting the participation of both transporters in ciliary Ca2+ clearance, and suggesting that both molecules localize close to the CNG channel. Chemosensory transducisomes provide a physical basis for the low amplification and for the linearity of odor responses at low odor concentrations.

Neuronal generator patterns of olfactory event-related brain potentials in schizophrenia

To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose-referenced 30-channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during detection of hydrogen sulfide (constant-flow olfactometer, 200 ms unirhinal exposure). Event-related potentials (ERPs) were transformed to reference-free current source density (CSD) waveforms and analyzed by unrestricted Varimax-PCA. Participants indicated when they perceived a high (10 ppm) or low (50% dilution) odor concentration. Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid-parietal P2 source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia.

Frequency Transitions in Odor-Evoked Neural Oscillations

In many species, sensory stimuli elicit the oscillatory synchronization of groups of neurons. What determines the properties of these oscillations? In the olfactory system of the moth, we found that odors elicited oscillatory synchronization through a neural mechanism like that described in locust and Drosophila. During responses to long odor pulses, oscillations suddenly slowed as net olfactory receptor neuron (ORN) output decreased; thus, stimulus intensity appeared to determine oscillation frequency. However, changing the concentration of the odor had little effect upon oscillatory frequency. Our recordings in vivo and computational models based on these results suggested that the main effect of increasing odor concentration was to recruit additional, less well-tuned ORNs whose firing rates were tightly constrained by adaptation and saturation. Thus, in the periphery, concentration is encoded mainly by the size of the responsive ORN population, and oscillation frequency is set by the adaptation and saturation of this response.