Abstract: The chemical senses (smell and taste) have evolved complex repertoires of chemosensory receptors — G-protein coupled receptors with a seven-transmembrane domain structure. In the mouse, ∼1,000 odorant receptors are dedicated to the conventional sense of smell, ∼300 vomeronasal receptors mediate the detection of chemical stimuli (such as pheromones) by the vomeronasal organ, and ∼40 taste receptors are implicated in bitter, sweet and umami taste. Nearly all receptor genes have now been identified as the result of genome sequencing, but few receptor–ligand interactions have been characterized. Targeted expression of the green fluorescent protein in chemosensory cells is a promising approach to achieve this objective.

Abstract: Molecular genetics has revealed a precise stereotypy in the projection of primary olfactory sensory neurons onto secondary neurons. A major challenge is to understand how this mapping translates into odor responses in these second-order neurons. We investigated this question in Drosophila using whole-cell recordings in vivo. We observe that monomolecular odors generally elicit responses in large ensembles of antennal lobe neurons. Comparison of odor-evoked activity from afferents and postsynaptic neurons in the same glomerulus revealed that second-order neurons display broader tuning and more complex responses than their primary afferents. This indicates a major transformation of odor representations, implicating lateral interactions within the antennal lobe.

Abstract: Objectives/Hypothesis: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Th ...

Abstract: Objectives/Hypothesis: Goals of the study were to evaluate the frequency of olfactory dysfunction in a large representative population without sinonasal complaints and to investigate the extent to which general pathological conditions, medications, and aging influence olfaction. Study Design: Prospective. Methods: Results based on an odor identification test (“Sniffin' Sticks”) were reported from 1240 subjects. The subjects presented themselves to an otorhinolaryngology outpatient clinic with relatively mild and transitory complaints unrelated to the upper airways. A detailed otorhinolaryngological examination in combination with a standardized interview further ascertained that these patients had no rhinological problems or symptoms relating to sinonasal disease. Results: Apart from the confirmation of the effects of age, gender, and certain otorhinolaryngological diseases on the sense of smell, the study results revealed that certain general diseases (liver diseases, nonotolaryngological cancers) appear to influence olfactory function, whereas other diseases or disorders have little or no impact on olfaction (hypertension, cardiovascular problems). Conclusion: The data in the study revealed that olfactory dysfunction among subjects under 65 years of age is more frequent than previously reported.

Abstract: Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates.

Abstract: Hyposmia is one of the most prevalent symptoms of Parkinson's disease. It may occur even before the motor symptoms start. To determine whether the olfactory dysfunctions, like the motor symptoms, are associated with a loss of dopamine, the number of dopaminergic cells in the olfactory bulb of Parkinson's disease patients was studied using tyrosine hydroxylase immunohistochemistry. The quantitative analysis reveals that the total number of tyrosine hydroxylase-immunoreactive neurons in the olfactory bulb is twice as high in Parkinson patients compared to age and gender-matched controls. Because dopamine is known to inhibit olfactory transmission in the olfactory glomeruli, we suggest that the increase of dopaminergic neurons in the olfactory bulb is responsible for the hyposmia in Parkinson patients. The increase of dopamine in the olfactory bulb explains why olfaction does not improve with levodopa therapy.

Abstract: Among birds, the Procellariiform seabirds (petrels, albatrosses, and shearwaters) are prime candidates for using chemical cues for individual recognition These birds have an excellent olfactory sense, and a variety of species nest in burrows that they can recognize by smell However, the nature of the olfactory signature--the scent that makes one burrow smell more like home than another--has not been established for any species Here, we explore the use of intraspecific chemical cues in burrow recognition and present evidence for partner-specific odor recognition in a bird

Abstract: Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.

Abstract: Anopheles gambiae is a highly anthropophilic mosquito responsible for the majority of malaria transmission in Africa. The biting and host preference behavior of this disease vector is largely influenced by its sense of smell, which is presumably facilitated by G protein-coupled receptor signaling [Takken, W. & Knols, B. (1999) Annu. Rev. Entomol. 44, 131-157]. Because of the importance of host preference to the mosquitoes' ability to transmit disease, we have initiated studies intended to elucidate the molecular mechanisms underlying olfaction in An. gambiae. In the course of these studies, we have identified a number of genes potentially involved in signal transduction, including a family of candidate odorant receptors. One of these receptors, encoded by GPRor7 (hereafter referred to as AgOr7), is remarkably similar to an odorant receptor that is expressed broadly in olfactory tissues and has been identified in Drosophila melanogaster and other insects [Krieger, J., Klink, O., Mohl, C., Raming, K. & Breer, H. (2003) J. Comp. Physiol. A 189, 519-526; Vosshall, L. B., Amrein, H., Morozov, P. S., Rzhetsky, A. & Axel, R. (1999) Cell 96, 725-736]. We have observed AgOr7 expression in olfactory and gustatory tissues in adult An. gambiae and during several stages of the mosquitoes' development. Within the female adult peripheral chemosensory system, antiserum against the AgOR7 polypeptide labels most sensilla of the antenna and maxillary palp as well as a subset of proboscis sensilla. Furthermore, AgOR7 antiserum labeling is observed within the larval antenna and maxillary palpus. These results are consistent with a role for AgOr7 in both olfaction and gustation in An. gambiae and raise the possibility that AgOr7 orthologs may also be of general importance to both modalities of chemosensation in other insects.

Abstract: Over the last ten years, methods of cerebral imaging have revolutionized our knowledge of cognitive processes in humans. An impressive number of papers dealing with cerebral imaging for olfaction have been published to date. Whereas the early works revealed those structures participating in the processing of odours presented passively to subjects, researchers later recorded brain activity when subjects performed specific olfactory tasks based on memory, emotion and identification. From these results, we suggest that there is a dissociation of olfactory processes, with involvement of the right hemisphere in memory processes and the left hemisphere in emotional processes. The review concludes with a summary of how these lateralized processes are consistent with the gestalt-nature of our olfactory perception.

Abstract: Humans and other mammals perceive a vast number of volatile chemicals as having distinct odors. This ability derives from the existence of a large family of olfactory receptors that number about 350 in man and 1000 in mice. Individual odorants activate distinct combinations of olfactory receptors, generating an immense array of combinatorial receptor codes that define odorant identities. Sensory neurons in the nose express only one receptor type each and connect to the olfactory bulb in a spatially organized manner that yields a stereotyped sensory map. A secondary projection from the bulb to the cortex transforms receptor inputs, generating another, different stereotyped map that may permit the integration of inputs from combinations of receptors. Another olfactory structure in the nasal septum of animals, the vomeronasal organ, has two additional receptor families that detect pheromones and induce hormonal and behavioral responses through a different projection to the brain.

Abstract: We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.

Abstract: In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex.

Abstract: Purpose of review Marked olfactory dysfunction (hyposmia) is a frequent and early abnormality in Parkinson's disease. We review recent advances related to its cause and its clinical relevance with respect to the differential diagnosis of Parkinsonian syndromes.Recent findings Marked olfactory dysfunction occurs in Parkinson's disease and dementia with Lewy bodies but is not found in progressive supranuclear palsy and corticobasal degeneration. In multiple system atrophy, the deficit is mild and indistinguishable from cerebellar syndromes of other aetiologies, including the spinocerebllar ataxias. This is in keeping with evidence of cerebellar involvement in olfactory processing, which may also help to explain recent findings of mild olfactory dysfunction in essential tremor. Smell testing remains, however, a clinically relevant tool in the differential diagnosis of indeterminate tremors. Intact olfaction has also been reported recently in Parkin disease (PARK 2) and vascular Parkinsonism. The relevance of sniffing ability to olfaction and a possible role of increased tyrosine hydroxylase and dopamine in parts of the olfactory bulb are issues of current interest with respect to pathophysiology. The early or 'pre-clinical' detection of Parkinson's disease is increasingly recognized as an area in which olfactory testing may be of value.Summary Research findings have confirmed a role for olfactory testing in the differential diagnosis of movement disorders, and suggest that this approach is currently underused in clinical practice. Validated test batteries are now available that may prove to be of practical use in the differential diagnosis of Parkinsonian syndromes and indeterminate tremors.

Abstract: Odors seem to be perceived differently when presented ortho- or retronasally. In this study, stimuli of controlled concentration and duration were applied in either the anterior nasal cavity or epipharynx by means of air-dilution olfactometry. Stimulus concentration was monitored in the olfactory cleft. In Experiment 1, odor thresholds to a food (chocolate) and a nonfood (lavender) odor were lower for orthonasal, compared with retronasal, stimulation. In Experiment 2, intensity ratings to suprathreshold odor concentrations were significantly higher for orthonasal than for retronasal stimulation with hydro- hydrogen sulfide, but not phenyl ethyl alcohol. Accordingly, amplitudes and latencies of olfactory event-related gen potentials to retronasal stimuli were found to be smaller and prolonged, respectively. This indicates differential processing of olfactory stimuli presented through the retronasal or orthonasal routes. )

Abstract: We propose a theoretical framework for odor classification in the olfactory system of insects. The classification task is accomplished in two steps. The first is a transformation from the antennal lobe to the intrinsic Kenyon cells in the mushroom body. This transformation into a higher-dimensional space is an injective function and can be implemented without any type of learning at the synaptic connections. In the second step, the encoded odors in the intrinsic Kenyon cells are linearly classified in the mushroom body lobes. The neurons that perform this linear classification are equivalent to hyperplanes whose connections are tuned by local Hebbian learning and by competition due to mutual inhibition. We calculate the range of values of activity and size of the network required to achieve efficient classification within this scheme in insect olfaction. We are able to demonstrate that biologically plausible control mechanisms can accomplish efficient classification of odors.

Abstract: Our understanding of the molecular basis of chemical signal recognition in insects has been greatly expanded by the recent discovery of olfactory receptors (Ors). Since the discovery of the complete repertoire of Drosophila melanogaster Ors, candidate Ors have been identified from at least 12 insect species from four orders (Coleoptera, Lepidoptera, Diptera, and Hymenoptera), including species of economic or medical importance. Although all Ors share the same G-protein coupled receptor structure with seven transmembrane domains, they present poor sequence homologies within and between species, and have been identified mainly through genomic data analyses. To date, D. melanogaster remains the only insect species where Ors have been extensively studied, from expression pattern establishment to functional investigations. These studies have confirmed several observations made in vertebrates: one Or type is selectively expressed in a subtype of olfactory receptor neurons, and one olfactory neuron expresses only one type of Or. In addition, all olfactory neurons expressing one Or type converge to the same glomerulus in the antennal lobe. The olfactory mechanism, thus, appears to be conserved between insects and vertebrates. Although Or functional studies are in their initial stages in insects (mainly Drosophila), insects appear to be good models to establish fundamental concepts of olfaction with the development of powerful genetic, imaging, and behavioral tools. This new field of study will greatly contribute to the understanding of insect chemical communication mechanisms, particularly with agricultural pests and disease vectors, and could result in future strategies to reduce their negative effects.

Abstract: The terms "microsmatic" and "macrosmatic" refer to species with lesser or greater levels, respectively, of olfactory function. Historically, primates are considered microsmats (olfactory sense reduced) with a concomitant increased emphasis on vision. The olfactory bulbs (forebrain centers that receive peripheral olfactory input) are proportionately smaller in primates compared to most other mammals. Similarly, the regions of the nasal cavity that are covered with olfactory epithelium (containing receptor cells) have proportionately less surface area in primates than other mammals. Thus, the generalization that primates are microsmatic is most frequently stated in terms of the proportional rather than absolute size of olfactory structures. Yet the importance of scaling to body size is unclear in regard to the chemical senses such as the olfactory or vomeronasal systems-do chemosensory structures such as olfactory bulbs and olfactory epithelium exhibit the same neural relationship to body mass that is seen for neural tissues that supply innervation to musculature or the skin? Previous studies examining neuronal density, volume, and/or surface area of the olfactory epithelium illustrate that different conclusions may be supported based on the parameter used. Plots of olfactory bulb volume versus body mass that generated for large-scale taxonomic studies or growth studies benefit from body mass (or total brain volume) with a comparative perspective. However, our examination of proportional versus absolute measurements implies that in comparisons within taxa, body size adjustments needlessly distort the data. As a final consideration, another embryonic derivative of the nasal placode, the vomeronasal organ, may warrant consideration regarding a definition of microsomia versus macrosomia.

Abstract: Aedes aegypti is a highly anthropophilic mosquito responsible for the transmission of dengue and yellow fever around the world. Like other mosquitoes, the biting and host preference behaviors of this disease vector are largely influenced by its sense of smell, which is presumably facilitated by G protein-coupled receptor signaling cascades. Here, we report the identification and characterization of AaOr7, the first candidate odorant receptor from Ae. aegypti. This receptor displays extremely high primary amino acid conservation with AgOr7 another candidate odorant receptor identified in the Aftrotropical malaria vector, Anopheles gambiae as well as several previously identified candidate odorant receptors in Drosophila melanogaster and other insects. Its transcript is expressed in adult chemosensory tissues and during several stages of Ae. aegypti development. Within the adult olfactory system, AaOr7 protein is found specifically within most antennal and maxillary palp sensilla, as well as in a subset of proboscis sensilla. These results are consistent with a role for AaOr7 in olfaction and gustation supporting the hypothesis that AaOr7 and its orthologs may be of general importance to chemosensory processes throughout the lifetime of an insect.

Abstract: In the insect antennal lobe, odor discrimination depends on the ability of the brain to read neural activity patterns across arrays of uniquely identifiable olfactory glomeruli. Less is understood about the complex temporal dynamics and interglomerular interactions that underlie these spatial patterns. Using neural-ensemble recording, we show that the evoked firing patterns within and between groups of glomeruli are odor dependent and organized in both space and time. Simultaneous recordings from up to 15 units per ensemble were obtained from four zones of glomerular neuropil in response to four classes of odorants: pheromones, monoterpenoids, aromatics, and aliphatics. Each odor class evoked a different pattern of excitation and inhibition across recording zones. The excitatory response field for each class was spatially defined, but inhibitory activity was spread across the antennal lobe, reflecting a center-surround organization. Some chemically related odorants were not easily distinguished by their spatial patterns, but each odorant evoked transient synchronous firing across a uniquely different subset of ensemble units. Examination of 535 cell pairs revealed a strong relationship between their recording positions, temporal correlations, and similarity of odor response profiles. These findings provide the first definitive support for a nested architecture in the insect olfactory system that uses both spatial and temporal coordination of firing to encode chemosensory signals. The spatial extent of the representation is defined by a stereotyped focus of glomerular activity for each odorant class, whereas the transient temporal correlations embedded within the ensemble provide a second coding dimension that can facilitate discrimination between chemically similar volatiles.

Abstract: Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called “troposmia”) or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis.

Abstract: The two pairs of sensory neurons of C. elegans , AWA and AWC, that mediate odorant attraction, express six Gα-subunits, suggesting that olfaction is regulated by a complex signaling network. Here, we describe the cellular localization and functions of the six olfactory Gα-subunits: GPA-2, GPA-3, GPA-5, GPA-6, GPA-13, and ODR-3. All except GPA-6 localize to sensory cilia, suggesting a direct role in sensory transduction. GPA-2, GPA-3, GPA-5, and GPA-6 are also present in cell bodies and axons and GPA-5 specifically localizes to synaptic sites. Analysis of animals with single- to sixfold loss-of-function mutations shows that olfaction involves a balance between multiple stimulatory and inhibitory signals. ODR-3 constitutes the main stimulatory signal and is sufficient for the detection of odorants. GPA-3 forms a second stimulatory signal in the AWA and AWC neurons, also sufficient for odorant detection. In AWA, signaling is suppressed by GPA-5. In AWC, GPA-2 and GPA-13 negatively and positively regulate signaling, respectively. Finally, we show that only ODR-3 plays a role in cilia morphogenesis. Defects in this process are, however, independent of olfactory behavior. Our findings reveal the existence of a complex signaling network that controls odorant detection by C. elegans .