Olfactory Adaptation Research Articles

Olfactory cilia, regulation and control of olfaction.

The sense of smell is still considered a fuzzy sensation. Softly wafting aromas can stimulate the appetite and trigger memories; however, there are many unexplored aspects of its underlying mechanisms, and not all of these have been elucidated. Although the final sense of smell takes place in the brain, it is greatly affected during the preliminary stage, when odorants are converted into electrical signals. After signal conversion through ion channels in olfactory cilia, action potentials are generated through other types of ion channels located in the cell body. Spike trains through axons transmit this information as digital signals to the brain, however, before odorants are converted into digital electric signals, such as an action potential, modification of the transduction signal has already occurred. This review focuses on the early stages of olfactory signaling. Modification of signal transduction mechanisms and their effect on the human sense of smell through three characteristics (signal amplification, olfactory adaptation, and olfactory masking) produced by olfactory cilia, which is the site of signal transduction are being addressed in this review.

Decomposition of an odorant in olfactory perception and neural representation.

Molecules-the elementary units of substances-are commonly considered the units of processing in olfactory perception, giving rise to undifferentiated odour objects invariant to environmental variations. By selectively perturbing the processing of chemical substructures with adaptation ('the psychologist's microelectrode') in a series of psychophysical and neuroimaging experiments (458 participants), we show that two perceptually distinct odorants sharing part of their structural features become significantly less discernible following adaptation to a third odorant containing their non-shared structural features, in manners independent of olfactory intensity, valence, quality or general olfactory adaptation. The effect is accompanied by reorganizations of ensemble activity patterns in the posterior piriform cortex that parallel subjective odour quality changes, in addition to substructure-based neural adaptations in the anterior piriform cortex and amygdala. Central representations of odour quality and the perceptual outcome thus embed submolecular structural information and are malleable by recent olfactory encounters.

Phasic/tonic glial GABA differentially transduce for olfactory adaptation and neuronal aging

Phasic (fast) and tonic (sustained) inhibition of γ-aminobutyric acid (GABA) are fundamental for regulating day-to-day activities, neuronal excitability, and plasticity. However, the mechanisms and physiological functions of glial GABA transductions remain poorly understood. Here, we report that the AMsh glia in Caenorhabditis elegans exhibit both phasic and tonic GABAergic signaling, which distinctively regulate olfactory adaptation and neuronal aging. Through genetic screening, we find that GABA permeates through bestrophin-9/-13/-14 anion channels from AMsh glia, which primarily activate the metabolic GABAB receptor GBB-1 in the neighboring ASH sensory neurons. This tonic action of glial GABA regulates the age-associated changes of ASH neurons and olfactory responses via a conserved signaling pathway, inducing neuroprotection. In addition, the calcium-evoked, vesicular glial GABA release acts upon the ionotropic GABAA receptor LGC-38 in ASH neurons to regulate olfactory adaptation. These findings underscore the fundamental significance of glial GABA in maintaining healthy aging and neuronal stability.

Insulin signaling in dopaminergic neurons regulates extended memory formation in Caenorhabditis elegans.

Insulin alters several brain functions, and perturbations in insulin levels could be a precipitating factor for Parkinson's disease, a disease associated with the degeneration of dopaminergic neurons. It is unclear whether insulin alters the dopamine signaling pathway and modulates learning and memory. In Caenorhabditis elegans, daf-2 insulin receptor mutants have extended memory when trained for olfactory adaptation. In this study, we show that the absence of daf-2 receptors in dopamine neurons results in this unusual learning behavior. Our results show that insulin function in memory is dopamine-dependent. In the absence of the daf-2 receptor, the calcium influx in dopamine neurons shows an altered pattern resulting in memory recall for an extended period. These results indicate that learning and memory involve insulin-dopamine crosstalk. Imbalances in this pathway result in changes in memory recall.

Transcriptome analysis of Apis mellifera antennae reveals molecular divergence underlying the division of labour in worker bees.

The olfactory system plays a fundamental role in mediating insect behaviour. Worker bees exhibit an age-dependent division of labour, performing discrete sets of behaviours throughout their lifespan. The behavioural states of bees rely on their sense of the environment and chemical communication via their olfactory system, the antennae. However, the olfactory adaptation mechanism of worker bees during their behavioural development remains unclear. In this study, we conducted a comprehensive and quantitative analysis of antennal gene expression in the Apis mellifera of newly emerged workers, nurses, foragers and defenders using RNA-seq. We found that the antenna tissues of honey bees continued developing after transformation from newly emerged workers to adults. Additionally, we identified differentially expressed genes associated with bee development and division of labour. We validated that major royal jelly protein genes are highly and specifically expressed in nurse honey bee workers. Furthermore, we identified and validated significant alternative splicing events correlated with the development and division of labour. These findings provide a comprehensive transcriptome profile and a new perspective on the molecular mechanisms that may underlie the worker honey bee division of labour.

Patients with olfactory loss exhibit pronounced adaptation to chemosensory stimuli: an electrophysiological study.

Pronounced chemosensory adaptation affects many patients with olfactory loss. The study aimed to investigate adaptation to olfactory and trigeminal nasal stimuli in patients with olfactory loss in comparison to controls using electrophysiological measures. Thirty-four patients with olfactory loss (mean age ± SD = 59 ± 16 years) and 17 healthy volunteers (mean age ± SD = 50 ± 14 years) were recruited. Sniffin’ sticks test was used for evaluation of olfactory function and EEG-derived chemosensory event-related potentials were recorded. Intranasal stimuli were presented using high-precision, computer-controlled stimulators based on the principles of air-dilution olfactometry. Data were analyzed in two different approaches according to the relatively short or long inter-stimulus interval. A decreased peak amplitude or a prolonged latency was considered as an expression of adaptation. The majority of participants (88%) responded reliably to chemosensory stimulation. Patients with olfactory loss exhibited pronounced olfactory and trigeminal adaptation within the long-term design, without such effects in healthy controls. Odor sensitivity correlated with both olfactory and trigeminal amplitude changes: the worse the olfactory sensitivity, the more pronounced chemosensory adaptation. The results help to explain the patients’ complaints in terms of the fast adaptation towards chemosensory stimuli, for example during eating and drinking. The differences in adaptation in patients with olfactory loss and healthy controls could serve as a clinical criterion to gauge olfactory dysfunction.

Odor-evoked layer-specific fMRI activities in the awake mouse olfactory bulb

Awake rodent fMRI is increasingly common over the use of anesthesia since it permits behavioral paradigms and does not confound normal brain function or neurovascular coupling. It is well established that adequate acclimation to the loud fMRI environment and head fixation reduces stress in the rodents and allows for whole brain imaging with little contamination from motion. However, it is unknown whether high-resolution fMRI with increased susceptibility to motion and lower sensitivity can measure small, but spatially discrete, activations in awake mice. To examine this, we used contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI in the mouse olfactory bulb for its enhanced sensitivity and neural specificity. We determined that activation patterns in the glomerular layer to four different odors were spatially distinct and were consistent with previously established histological patterns. In addition, odor-evoked laminar activations were greatest in superficial layers that decreased with laminar depth, similar to previous observations. Interestingly, the fMRI response strengths in the granule cell layer were greater in awake mice than our previous anesthetized rat studies, suggesting that feedback neural activities were intact with wakefulness. We finally determined that fMRI signal changes to repeated odor exposure (i.e., olfactory adaptation) attenuated relatively more in the feedback granule cell layer compared to the input glomerular layer, which is consistent with prior observations. We, therefore, conclude that high-resolution CBVw fMRI can measure odor-specific activation patterns and distinguish changes in laminar activity of head and body restrained awake mice.

Segregation of Ca2+ signaling in olfactory signal transduction.

Olfactory signal transduction is conducted through a cAMP-mediated second messenger cascade. The cytoplasmic Ca2+ concentration increases through the opening of CNG channels, a phenomenon that underlies two major functions, namely, signal boosting and olfactory adaptation. Signal boosting is achieved by an additional opening of the Ca2+-activated Cl- channel whereas adaptation is regulated by Ca2+ feedback to the CNG channel. Thus, the influx of Ca2+ and the resultant increase in cytoplasmic Ca2+ levels play seemingly opposing effects: increasing the current while reducing the current through adaptation. The two functions could be interpreted as compensating for each other. However, in real cells, both functions should be segregated. Ca2+ dynamics in olfactory cilia need to be directly measured, but technical difficulties accompanying the thin structure of olfactory cilia have prevented systematic analyses. In this study, using a combination of electrophysiology, local photolysis of caged cAMP, and Ca2+ imaging, we found that free Ca2+ in the local ciliary cytoplasm decreased along with a reduction in the current containing Ca2+-activated Cl- components returning to the basal level, whereas Ca2+-dependent adaptation persisted for a longer period. The activity of Cl- channels is highly likely to be regulated by the free Ca2+ that is present only immediately after the influx through the CNG channel, and an exclusive interaction between Ca2+ and Ca2+-binding proteins that mediate the adaptation may modulate the adaptation lifetime.

Effect of Herbal Perfumes and Synthetic Perfumes on Attention and Cognitive Functions in Young Adults: A Sequential Cross-sectional Study

Introduction: Focused and sustained attention, executive function, working memory and task switching are important cognitive abilities. Efforts to enhance cognitive abilities, have engaged the scientific community since ages. Human beings are exposed to several fragrances and the perception of the sense of smell, plays an important role in the physiological effects of mood, stress, and working capacity. Perception of olfactory stimuli involves complex brain processing, which can be directly associated with cognition and emotion. Several Electroencephalogram (EEG) studies have revealed that, fragrances significantly modulate the activities of different brain waves and are responsible for various states of the brain. Aim: To objectively demonstrate the effect of olfactory stimulation with herbal (rose) perfume on attention and executive functions. Materials and Methods: This sequential cross-sectional study was conducted in the Department of Physiology at Osmania Medical College, Hyderabad, Telangana, India. The duration of the study was one month, from 16th August 2021 to 16th September 2021. Study included 40 healthy participants (15 males and 25 females), aged between 18-30 years to olfactory stimulation by herbal (rose) extract perfume and synthetic (rose) perfume, and the effects are assessed, using the psychophysiological tests viz., Rapid Serial Visual Presentation task (RSVP), Trail Making Tests (TMT) A&B, Ruff Figural Fluency Test (RFT), and compared with the baseline scores, which are then analysed using Paired t-test. The data was analysed by using Statistical Package for Social Sciences (SPSS) version 16.0. Results: Olfactory stimulation with herbal rose perfume enhances the attention and speed of processing, as shown by the nearly significant improvement in the performance of the TMT-A (p-value=0.05433), with decreased time taken to perform the test, whereas, the synthetic rose perfume enhanced the attention, speed, switching between tasks, cognitive fluency, and flexibility. This is evident by the significant improvement in the performance of the TMT-A (p-value=0.00326) and TMT-B (p-value=0.0001693), with decreased time taken to perform the tests. The derived index TMT (B-A), which removes the speed component and is a purer index of executive functions, also showed significant results (p-value=0.002092). Conclusion: The effects of herbal and synthetic rose olfactory stimulation have shown positive influence on the attention and cognitive functions and this finding can be applied to create student friendly learning environments, by providing pleasant stimuli through means of aromatic sprays delivering the odorant in a pulsatile manner at a frequency to overcome the ensuing olfactory adaptation.

Genomic insight into the nocturnal adaptation of the black-crowned night heron (Nycticorax nycticorax)

BackgroundThe black-crowned night heron (Nycticorax nycticorax) is an ardeid bird successfully adapted to the nocturnal environment. Previous studies had indicated that the eyes of the night herons have evolved several specialized morphological traits favoring nocturnal vision. However, the molecular mechanisms of the nocturnal vision adaptation of night herons remained inattentions. In this study, the whole genome of N. nycticorax was sequenced and comparative analyses were performed on the vision-related and olfactory receptor (OR) genes to understand the molecular mechanisms of the visual and olfactory adaptation of night herons.ResultsThe results indicated that a number of vision genes were under positive or relaxed selection in N. nycticorax, whereas a number of other vision genes were under relaxed or intensified selection in the boat-billed heron (Cochlearius cochlearius), which suggested that the two species adapt to nocturnality with different genetic mechanisms. The different selections acting on vision genes are probably associated with the enlargement of eye size and the enhancement of visual sensitivity in night herons. The analyses on olfactory receptor (OR) genes indicated that the total number of OR genes in the genomes of N. nycticorax and C. cochlearius were about half those in the little egret (Egretta garzetta), whereas the diversity of their OR genes was not remarkably different. Additionally, the number of expressed OR genes in the transcriptomes of N. nycticorax was also fewer than that in E. garzetta. These results suggest a reduced olfactory capability in night herons compared with E. garzetta.ConclusionsOur results provided evidence that several vision genes of the night herons were subjected to different natural selections, which can contribute to a better understanding of the genetic mechanisms of visual adaptions of the night heron. In addition, the finding of the reduced number of total and expressed OR genes in night herons may reflect a trade-off between olfaction and vision.

Impact of indoor aroma on students’ mood and learning performance

Indoor environment has an appreciable impact on occupants' mood, health and performance. Among numerous indoor environmental components, indoor air quality is often considered to be one of the most crucial ones. While odor is a decisive factor for evaluating perceived indoor air quality, its effects - particularly the positive effects of pleasant aromas - on human responses and performance have yet to be revealed. In this study, experiments were conducted to investigate the effect of indoor aroma on students' mood and learning performance. Participants comprised 76 university students and they performed two learning tasks under one of the four odor conditions: “control (aromaless)”, “rosemary”, “lemon”, and “peppermint.” First, the way in which students sense the indoor aroma in a study space was investigated using several mood scales, including odor intensity, pleasantness, preference, acceptability, and impression. Second, the influence of indoor aroma on learning and memory performance was quantitatively assessed using a reading task and a verbal memory task. Lastly, the impacts of odor preference on subjective evaluation and performance were explored. This experiment showed that subjective evaluations were significantly different before and after olfactory adaptation, particularly in the rosemary condition. Of all three aroma conditions, the lemon aroma had the highest preference and led to the highest scores in the memory task. Although the significant impact of indoor aroma on learning performance was not detected, our results indicated that pleasant aroma has the potential to enhance students’ mood and learning performance.

Differences in ASP1 expression and binding dynamics to queen mandibular pheromone HOB between Apis mellifera and Apis cerana workers reveal olfactory adaptation to colony organization

The eastern Apis cerana (Ac) and the western Apis mellifera (Am) are two closely related and most economically valuable honeybee species managed extensively worldwide. However, how worker bees of Ac and Am are adapted to their colony organization remains to be uncovered. Here, we found that the expression level of gene encoding antennae-specific proteins 1 (ASP1, a key regulator in recognizing queen mandibular pheromone) was positively correlated with the colony sizes in both bee species, and the expression level in Am was higher than that in Ac, suggesting that ASP1 may play an important role in maintaining colony homeostasis. Using competitive binding assay, molecular docking, and site-directed mutagenesis, we then confirmed the good binding affinities of both Ac-ASP1 and Am-ASP1 to methyl p-hydroxy benzoate (HOB), and Val115 was the key amino acid. However, the affinity of Am-ASP1 was stronger than that of Ac-ASP1. EAG analysis further demonstrated that antennae of Am worker bees had faster depolarization and repolarization in response to HOB stimulation. Taken together, these findings indicate that the differences in expression levels and binding dynamics allow ASP1 recognizing HOB to potentially serve as a specific regulator of colony organization in Ac and Am.

Behavioral Forgetting of Olfactory Learning Is Mediated by Interneuron-Regulated Network Plasticity in Caenorhabditis elegans.

Forgetting is important for animals to manage acquired memories to enable adaptation to changing environments; however, the neural network in mechanisms of forgetting is not fully understood. To understand the mechanisms underlying forgetting, we examined olfactory adaptation, a form of associative learning, in Caenorhabditis elegans. The forgetting of diacetyl olfactory adaptation in C. elegans is regulated by secreted signals from AWC sensory neurons via the TIR-1/JNK-1 pathway. These signals cause a decline of the sensory memory trace in AWA neurons, where diacetyl is mainly sensed. To further understand the neural network that regulates this forgetting, we investigated the function of interneurons downstream of AWA and AWC neurons. We found that a pair of interneurons, AIA, is indispensable for the proper regulation of behavioral forgetting of diacetyl olfactory adaptation. Loss or inactivation of AIA caused the impairment of the chemotaxis recovery after adaptation without causing severe chemotaxis defects in the naive animal. AWA Ca2+ imaging analyses suggested that loss or inactivation of AIA interneurons did not affect the decline of the sensory memory trace after the recovery. Furthermore, AIA responses to diacetyl were observed in naive animals and after the recovery, but not just after the conditioning, suggesting that AIA responses after the recovery are required for the chemotaxis to diacetyl. We propose that the functional neuronal circuit for attractive chemotaxis to diacetyl is changed temporally at the recovery phase so that AIA interneurons are required for chemotaxis, although AIAs are dispensable for attractive chemotaxis to diacetyl in naive animals.

The Voltage-Gated Calcium Channel EGL-19 Acts on Glia to Drive Olfactory Adaptation.

Calcium channelopathies have been strongly linked to cardiovascular, muscular, neurological and psychiatric disorders. The voltage-gated calcium channels (VGCC) are vital transducers of membrane potential changes to facilitate the dynamics of calcium ions and release of neurotransmitter. Whether these channels function in the glial cell to mediate calcium variations and regulate behavioral outputs, is poorly understood. Our results showed that odorant and mechanical stimuli evoked robust calcium increases in the amphid sheath (AMsh) glia from C. elegans, which were largely dependent on the L-Type VGCC EGL-19. Moreover, EGL-19 modulates the morphologies of both ASH sensory neurons and AMsh glia. Tissue-specific knock-down of EGL-19 in AMsh glia regulated sensory adaptability of ASH neurons and promoted olfactory adaptation. Our results reveal a novel role of glial L-Type VGCC EGL-19 on olfaction, lead to improved understanding of the functions of VGCCs in sensory transduction.

Effect of intra-nasal nitrilotriacetic acid trisodium salt in lowering elevated calcium cations and improving olfactory dysfunction in COVID-19 patients

PurposeAn association between COVID-19 and olfactory dysfunction has been noted in many patients worldwide. The olfactory adaptation process leads to an increase in intracellular calcium cation levels. Nitrilotriacetic acid trisodium salt has high selective chelation for calcium cations from olfactory mucus. The aim of this work is to test the effect of an intranasal nitrilotriacetic acid trisodium salt to lower the elevated calcium cations in COVID-19 patients with relevant symptoms of olfactory dysfunction.MethodsFifty-eight COVID-19 adult patients with relevant symptoms of olfactory dysfunction were enrolled in a prospective randomized controlled trial. They received a nasal spray containing either 0.9% sodium chloride or 2% nitrilotriacetic acid trisodium salt. Olfactory function was assessed before and after treatment using the Sniffin’ Sticks test. Quantitative analysis of calcium cation concentration in nasal secretions was performed using a carbon paste ion-selective electrode.ResultsAfter the application of nitrilotriacetic acid trisodium salt compared to sodium chloride, a significant improvement from functional anosmia to healthy normosmia with significant decrease in calcium cation concentration was observed.ConclusionsFurther collaborative research is needed to fully investigate the effect of an intranasal nitrilotriacetic acid trisodium salt in the treatment of olfactory disorders.

Deficiency in RCAT-1 Function Causes Dopamine Metabolism Related Behavioral Disorders in Caenorhabditis elegans.

When animals are faced with food depletion, food search-associated locomotion is crucial for their survival. Although food search-associated locomotion is known to be regulated by dopamine, it has yet to investigate the potential molecular mechanisms governing the regulation of genes involved in dopamine metabolism (e.g., cat-1, cat-2) and related behavioral disorders. During the studies of the pheromone ascaroside, a signal of starvation stress in C. elegans, we identified R02D3.7, renamed rcat-1 (regulator of cat genes-1), which had previously been shown to bind to regulatory sequences of both cat-1 and cat-2 genes. It was found that RCAT-1 (R02D3.7) is expressed in dopaminergic neurons and functions as a novel negative transcriptional regulator for cat-1 and cat-2 genes. When a food source becomes depleted, the null mutant, rcat-1(ok1745), exhibited an increased frequency of high-angled turns and intensified area restricted search behavior compared to the wild-type animals. Moreover, rcat-1(ok1745) also showed defects in state-dependent olfactory adaptation and basal slowing response, suggesting that the mutants are deficient in either sensing food or locomotion toward food. However, rcat-1(ok1745) has normal cuticular structures and locomotion genes. The discovery of rcat-1 not only identifies a new subtype of dopamine-related behaviors but also provides a potential therapeutic target in Parkinson’s disease.

Palmitoylation as a post-translational modification of the K+-dependent Na+/Ca2+-exchanger 4

The K+-dependent Na+/Ca2+-exchanger (NCKX) family comprises five proteins (NCKX1-5) that play an important role in modulating Ca2+ efflux and in maintaining cellular Ca2+ homeostasis. NCKX4 has been shown to play a critical role in multiple physiological processes such as visual and olfactory signal termination and adaptation, tooth enamel formation, melanocortin-dependent satiety signalling, as well as age related cognitive function. However, how NCKX4 is regulated is an important but understudied question.

Transcriptome Analysis Reveals Olfactory System Expression Characteristics of Aquatic Snakes.

Animal olfactory systems evolved with changes in habitat to detect odor cues from the environment. The aquatic environment, as a unique habitat, poses a formidable challenge for olfactory perception in animals, since the higher density and viscosity of water. The olfactory system in snakes is highly specialized, thus providing the opportunity to explore the adaptive evolution of such systems to unique habitats. To date, however, few studies have explored the changes in gene expression features in the olfactory systems of aquatic snakes. In this study, we carried out RNA sequencing of 26 olfactory tissue samples (vomeronasal organ and olfactory bulb) from two aquatic and two non-aquatic snake species to explore gene expression changes under the aquatic environment. Weighted gene co-expression network analysis showed significant differences in gene expression profiles between aquatic and non-aquatic habitats. The main olfactory systems of the aquatic and non-aquatic snakes were regulated by different genes. Among these genes, RELN may contribute to exploring gene expression changes under the aquatic environment by regulating the formation of inhibitory neurons in the granular cell layer and increasing the separation of neuronal patterns to correctly identify complex chemical information. The high expression of TRPC2 and V2R family genes in the accessory olfactory systems of aquatic snakes should enhance their ability to bind water-soluble odor molecules, and thus obtain more information in hydrophytic habitats. This work provides an important foundation for exploring the olfactory adaptation of snakes in special habitats.

Olfactory adaptation: recordings from the human olfactory epithelium

PurposeOlfactory adaptation is a peripheral (at the epithelium level) or a central (at the brain level) mechanism resulting from repeated or prolonged odorous exposure that can induce a perceptual decrease. The aim of this study was to assess whether a peripheral adaptation occurs when an odor is repeated ten times. Moreover, the specificity of the peripheral adaptation to the nature of the odorant was investigated.MethodsFour odorants (eugenol, manzanate, ISO E Super and phenylethanol) were presented using precisely controlled air-dilution olfactometry. They differed in terms of their physicochemical properties. Electrophysiological recordings were made at the level of the olfactory mucosa, the so-called electro-olfactogram (EOG). Thirty-five right-handed participants were recruited.ResultsSixty-nine percent of the participants presented at least one EOG, whatever the odor condition. The EOG amplitude did not significantly decrease over 10 repeated exposures to any odorant. The intensity ratings tended to decrease over stimulations for manzanate, PEA, and eugenol. No correlation was found between the mean EOG amplitudes and the mean intensity ratings. However, the presence of EOG amplitude decreases over stimulations for few subjects suggests that peripheral adaptation might exist.ConclusionOverall, our results did not establish a clear peripheral adaptation measured with EOG but indicate the eventuality of such an effect.

The Mammalian Olfactory Bulb Contributes to the Adaptation of Odor Responses: A Second Perceptual Computation Carried Out by the Bulb

While humans and other mammals exhibit adaptation to odorants, the neural mechanisms and brain locations involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted to the brain. An alternative possibility is that adaptation occurs because of processing in the brain. We made an initial test of these possibilities using a two-color imaging strategy to simultaneously measure the activity of the olfactory receptor nerve terminals (input to the bulb) and mitral/tufted cell apical dendrites (output from the bulb) in anesthetized and awake mice. Repeated odor stimulation at the same concentration resulted in a decline in the bulb output, while the input remained relatively stable. Thus, the mammalian olfactory bulb appears to participate in generating the perception of olfactory adaptation under this stimulus condition. Similar experiments conducted previously showed that the bulb may also participate in the perception of concentration invariance of odorant recognition (Storace and Cohen, 2017); thus, the bulb is simultaneously carrying out more than one computation, as is true of other mammalian brain regions and perhaps is the case for all animals with sophisticated nervous systems. However, in contrast with other sensory systems (Van Essen et al., 1992), the very first processing stage in the olfactory system has an output that may directly represent perceptions.