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Showing papers on "Olfaction published in 2013"


Book
14 Oct 2013
TL;DR: The implications of Taste and Smell Disorders, Conditioned Flavour Aversions, Head Injury and Taste, Iatrogenic Causes of Taste Disturbances: Radiation Therapy, Surgery, Medication Other Chemosensory Systems are examined.
Abstract: Part 1 Olfaction: Anatomy, Biochemistry and Physiology - Olfactory Mucosa: Composition, Enzymatic Localization and Metabolism, Anatomy of the Human Nasal Passages, Anatomy and Ultrastructure of the Human Olfactory Neuroepithelium, Functional Anatomy, Central Connections, and Neurochemistry of the Mammalian Olfactory Bulb, The Molecular Mechanisms of Olfactory Signal Transduction, Developmental Anatomy of the Olfactory System Human Psychophysics and Measurement of Odor-Induced Responses - Current Trends In the Measurement of Olfactory Function, Modern Approaches to Air Dilution Olfactometry, Olfactory Adaptation, Perception of Odor Mixtures, Olfaction and Development of Social Preferences in Neonatal Organisms, The Genetics of Olfactory Perception Clinical Applications and Perspectives - Clinical Disorders of Olfaction - A Review, Viruses and the Olfactory System, Evaluation of Olfactory Deficits by Medical Imaging, Rhinological Considerations and Upper Airway Physical Examination of Patients with Olfactory Disorders, Distorted Olfactory Perception, Deprivation and the Olfactory System, Nasal Airway Dynamics and Olfactory Function. Part 2 Gustation: Anatomy, Biochemistry, Development, Genetics, and Physiology - Saliva: Its Function and Disorders, Anatomy of the Peripheral Taste System, Central Taste Anatomy and Neurophysiology, Receptor Mechanisms in Gustation, Transduction of Taste Stimuli by Receptor Cells in the Gustatory System Human Psychophysics and Measurement of Testant-Induced Responses - Current Trends in Measuring Taste, Perception of Taste Mixtures, Ontogeny of Human Taste Perception clinical Applications and Perspectives - nutritional implications of Taste and Smell Disorders, Conditioned Flavour Aversions, Head Injury and Taste, Iatrogenic Causes of Taste Disturbances: Radiation Therapy, Surgery, Medication Other Chemosensory Systems. (Part Contents).

734 citations


Journal ArticleDOI
Rachel Wilson1
TL;DR: This review summarizes the neurophysiology of the first two layers of this system: the peripheral olfactory receptor neurons and their postsynaptic targets in the antennal lobe and suggests some general principles with broad relevance to early sensory processing in other modalities.
Abstract: In the olfactory system of Drosophila melanogaster, it is relatively straightforward to target in vivo measurements of neural activity to specific processing channels. This, together with the numerical simplicity of the Drosophila olfactory system, has produced rapid gains in our understanding of Drosophila olfaction. This review summarizes the neurophysiology of the first two layers of this system: the peripheral olfactory receptor neurons and their postsynaptic targets in the antennal lobe. We now understand in some detail the cellular and synaptic mechanisms that shape odor representations in these neurons. Together, these mechanisms imply that interesting neural adaptations to environmental statistics have occurred. These mechanisms also place some fundamental constraints on early sensory processing that pose challenges for higher brain regions. These findings suggest some general principles with broad relevance to early sensory processing in other modalities.

328 citations


Journal ArticleDOI
TL;DR: Glutamatergic neurons are abundant in the Drosophila central nervous system, but their physiological effects are largely unknown, and the existence of two parallel inhibitory transmitter systems may increase the range and flexibility of synaptic inhibition.
Abstract: Glutamatergic neurons are abundant in the Drosophila central nervous system, but their physiological effects are largely unknown. In this study, we investigated the effects of glutamate in the Drosophila antennal lobe, the first relay in the olfactory system and a model circuit for understanding olfactory processing. In the antennal lobe, one-third of local neurons are glutamatergic. Using in vivo whole-cell patch clamp recordings, we found that many glutamatergic local neurons are broadly tuned to odors. Iontophoresed glutamate hyperpolarizes all major cell types in the antennal lobe, and this effect is blocked by picrotoxin or by transgenic RNAi-mediated knockdown of the GluClα gene, which encodes a glutamate-gated chloride channel. Moreover, antennal lobe neurons are inhibited by selective activation of glutamatergic local neurons using a nonnative genetically encoded cation channel. Finally, transgenic knockdown of GluClα in principal neurons disinhibits the odor responses of these neurons. Thus, glutamate acts as an inhibitory neurotransmitter in the antennal lobe, broadly similar to the role of GABA in this circuit. However, because glutamate release is concentrated between glomeruli, whereas GABA release is concentrated within glomeruli, these neurotransmitters may act on different spatial and temporal scales. Thus, the existence of two parallel inhibitory transmitter systems may increase the range and flexibility of synaptic inhibition.

224 citations


Journal ArticleDOI
TL;DR: Identification of proteins important for chemoreception in two of the most destructive forest pests, sharing many semiochemicals, is especially important as they might represent novel targets for population control.
Abstract: The European spruce bark beetle, Ips typographus, and the North American mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae: Scolytinae), are severe pests of coniferous forests. Both bark beetle species utilize aggregation pheromones to coordinate mass-attacks on host trees, while odorants from host and non-host trees modulate the pheromone response. Thus, the bark beetle olfactory sense is of utmost importance for fitness. However, information on the genes underlying olfactory detection has been lacking in bark beetles and is limited in Coleoptera. We assembled antennal transcriptomes from next-generation sequencing of I. typographus and D. ponderosae to identify members of the major chemosensory multi-gene families. Gene ontology (GO) annotation indicated that the relative abundance of transcripts associated with specific GO terms was highly similar in the two species. Transcripts with terms related to olfactory function were found in both species. Focusing on the chemosensory gene families, we identified 15 putative odorant binding proteins (OBP), 6 chemosensory proteins (CSP), 3 sensory neuron membrane proteins (SNMP), 43 odorant receptors (OR), 6 gustatory receptors (GR), and 7 ionotropic receptors (IR) in I. typographus; and 31 putative OBPs, 11 CSPs, 3 SNMPs, 49 ORs, 2 GRs, and 15 IRs in D. ponderosae. Predicted protein sequences were compared with counterparts in the flour beetle, Tribolium castaneum, the cerambycid beetle, Megacyllene caryae, and the fruit fly, Drosophila melanogaster. The most notable result was found among the ORs, for which large bark beetle-specific expansions were found. However, some clades contained receptors from all four beetle species, indicating a degree of conservation among some coleopteran OR lineages. Putative GRs for carbon dioxide and orthologues for the conserved antennal IRs were included in the identified receptor sets. The protein families important for chemoreception have now been identified in three coleopteran species (four species for the ORs). Thus, this study allows for improved evolutionary analyses of coleopteran olfaction. Identification of these proteins in two of the most destructive forest pests, sharing many semiochemicals, is especially important as they might represent novel targets for population control.

172 citations


Journal ArticleDOI
TL;DR: Exciting new findings have revealed how the neurons and circuits of the piriform cortex process odor information, demonstrating that, despite its superficial simplicity, the Piriform cortex is a remarkably subtle and intricate neural circuit.

169 citations


Journal ArticleDOI
23 May 2013-Nature
TL;DR: The findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours, and reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.
Abstract: Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

168 citations


Journal ArticleDOI
TL;DR: It is shown that zebrafish, a vertebrate model system, exhibit powerful and innate avoidance behavior to both diamines, and a high-affinity olfactory receptor for cadaverine is identified, providing a molecular basis for studying neural circuits connecting sensation, perception, and innate behavior.
Abstract: Carrion smell is strongly repugnant to humans and triggers distinct innate behaviors in many other species. This smell is mainly carried by two small aliphatic diamines, putrescine and cadaverine, which are generated by bacterial decarboxylation of the basic amino acids ornithine and lysine. Depending on the species, these diamines may also serve as feeding attractants, oviposition attractants, or social cues. Behavioral responses to diamines have not been investigated in zebrafish, a powerful model system for studying vertebrate olfaction. Furthermore, olfactory receptors that detect cadaverine and putrescine have not been identified in any species so far. Here, we show robust olfactory-mediated avoidance behavior of zebrafish to cadaverine and related diamines, and concomitant activation of sparse olfactory sensory neurons by these diamines. The large majority of neurons activated by low concentrations of cadaverine expresses a particular olfactory receptor, trace amine-associated receptor 13c (TAAR13c). Structure-activity analysis indicates TAAR13c to be a general diamine sensor, with pronounced selectivity for odd chains of medium length. This receptor can also be activated by decaying fish extracts, a physiologically relevant source of diamines. The identification of a sensitive zebrafish olfactory receptor for these diamines provides a molecular basis for studying neural circuits connecting sensation, perception, and innate behavior.

159 citations


Journal ArticleDOI
TL;DR: The aim of the present study was to statistically combine all published data on functional neuroimaging of olfaction to provide a probability map reflecting the state of the field to date, and to investigate whether these systematically affected the reported findings.

155 citations


Journal ArticleDOI
TL;DR: This study, for the first time using emotional scales that are appropriate to the olfactory domain, brings new insights into the variability of affective responses to odors and its relationship to odor knowledge.
Abstract: Emotion and odor scales (EOS) measuring odor-related affective feelings were recently developed for three different countries (Switzerland, United Kingdom, and Singapore). The first aim of this study was to investigate gender and cultural differences in verbal affective response to odors, measured with EOS and the usual pleasantness scale. To better understand this variability, the second aim was to investigate the link between affective reports and olfactory knowledge (familiarity and identification). Responses of 772 participants smelling 56-59 odors were collected in the three countries. Women rated odors as more intense and identified them better in all countries, but no reliable sex differences were found for verbal affective responses to odors. Disgust-related feelings revealed odor-dependent sex differences, due to sex differences in identification and categorization. Further, increased odor knowledge was related to more positive affects as reported with pleasantness and odor-related feeling evaluations, which can be related to top-down influences on odor representation. These top-down influences were thought, for example, to relate to beliefs about odor properties or to categorization (edible vs. nonedible). Finally, the link between odor knowledge and olfactory affect was generally asymmetrical and significant only for pleasant odors, not for unpleasant ones that seemed to be more resistant to cognitive influences. This study, for the first time using emotional scales that are appropriate to the olfactory domain, brings new insights into the variability of affective responses to odors and its relationship to odor knowledge.

151 citations


Journal ArticleDOI
TL;DR: It is posit that modest, yet cumulative, alterations of AgOr transcript levels modulate peripheral odor coding resulting in biologically relevant behavioral effects, and this results demonstrate that highly quantitative, RNAseq transcript abundance data can be successfully integrated with functional data to generate testable hypotheses.
Abstract: Olfactory-driven behaviors are central to the lifecycle of the malaria vector mosquito Anopheles gambiae and are initiated by peripheral signaling in the antenna and other olfactory tissues. To continue gaining insight into the relationship between gene expression and olfaction, we have performed cohort comparisons of antennal transcript abundances at five time points after a blood meal, a key event in both reproduction and disease transmission cycles. We found that more than 5,000 transcripts displayed significant abundance differences, many of which were correlated by cluster analysis. Within the chemosensory gene families, we observed a general reduction in the level of chemosensory gene transcripts, although a subset of odorant receptors (AgOrs) was modestly enhanced in post–blood-fed samples. Integration of AgOr transcript abundance data with previously characterized AgOr excitatory odorant response profiles revealed potential changes in antennal odorant receptivity that coincided with the shift from host-seeking to oviposition behaviors in blood-fed female mosquitoes. Behavioral testing of ovipositing females to odorants highlighted by this synthetic analysis identified two unique, unitary oviposition cues for An. gambiae, 2-propylphenol and 4-methylcyclohexanol. We posit that modest, yet cumulative, alterations of AgOr transcript levels modulate peripheral odor coding resulting in biologically relevant behavioral effects. Moreover, these results demonstrate that highly quantitative, RNAseq transcript abundance data can be successfully integrated with functional data to generate testable hypotheses.

149 citations


Journal ArticleDOI
TL;DR: The investigation of the potential role of olfactory cues for navigation in wild birds is still at an early stage; however, the evidence collected so far suggests that Olfactory navigation might be a widespread mechanism in avian species.
Abstract: Forty years ago, Papi and colleagues discovered that anosmic pigeons cannot find their way home when released at unfamiliar locations. They explained this phenomenon by developing the olfactory navigation hypothesis: pigeons at the home loft learn the odours carried by the winds in association with wind direction; once at the release site, they determine the direction of displacement on the basis of the odours perceived locally and orient homeward. In addition to the old classical experiments, new GPS tracking data and observations on the activation of the olfactory system in displaced pigeons have provided further evidence for the specific role of olfactory cues in pigeon navigation. Although it is not known which odours the birds might rely on for navigation, it has been shown that volatile organic compounds in the atmosphere are distributed as fairly stable gradients to allow environmental odour-based navigation. The investigation of the potential role of olfactory cues for navigation in wild birds is still at an early stage; however, the evidence collected so far suggests that olfactory navigation might be a widespread mechanism in avian species. * Anosmic : Deprived of the sense of smell. Compass : A behavioural mechanism allowing the selection of a specific direction in space on the basis of an external reference, such as the sun azimuth and the geomagnetic field. Macrophage : A cell of the immune system. Navigational map : A behavioural mechanism allowing a subject to establish the current position with respect to the goal on the basis of environmental cues. Piriform cortex : The region of the brain, more precisely of the telencephalon, that receives direct input from the olfactory bulb. The piriform cortex is involved in the discrimination and memorization of odour stimuli. Trigeminal nerve : The fifth cranial nerve. It has three branches, with sensory (the ophthalmic nerve and the maxillary nerve) or sensory-motor (the mandibular nerve) functions. True navigation : The ability of a subject to reach a goal by calculating the goal position on the basis of local cues [the ‘map step’, according to Kramer's definition ([Kramer, 1953][1])] and by determining the goal direction in space (the ‘compass step’, according to Kramer's definition). Vanishing bearing : The direction of a released bird when vanishing from the observer's view at the release site. ZENK : An immediate early gene rapidly expressed in response to external stimuli. An increased expression of the ZENK protein in certain brain regions can be directly linked to neuronal activity. [1]: #ref-34

Journal ArticleDOI
TL;DR: These findings could constitute an olfactory etiology model of emotional disorders, as exaggerated emotion–olfaction interaction in negative mood states turns innocuous odors aversive, fueling anxiety and depression with rising ambient sensory stress.
Abstract: Phylogenetically the most ancient sense, olfaction is characterized by a unique intimacy with the emotion system. However, mechanisms underlying olfaction–emotion interaction remain unclear, especially in an ever-changing environment and dynamic internal milieu. Perturbing the internal state with anxiety induction in human subjects, we interrogated emotion-state-dependent olfactory processing in a functional magnetic resonance imaging (fMRI) study. Following anxiety induction, initially neutral odors become unpleasant and take longer to detect, accompanied by augmented response to these odors in the olfactory (anterior piriform and orbitofrontal) cortices and emotion-relevant pregenual anterior cingulate cortex. In parallel, the olfactory sensory relay adapts with increased anxiety, incorporating amygdala as an integral step via strengthened (afferent or efferent) connections between amygdala and all levels of the olfactory cortical hierarchy. This anxiety-state-dependent neural circuitry thus enables cumulative infusion of limbic affective information throughout the olfactory sensory progression, thereby driving affectively charged olfactory perception. These findings could constitute an olfactory etiology model of emotional disorders, as exaggerated emotion–olfaction interaction in negative mood states turns innocuous odors aversive, fueling anxiety and depression with rising ambient sensory stress.

Journal ArticleDOI
TL;DR: Chemical analysis in combination with a series of physiological and behavioral tests identify a chemical Leitmotiv that underlies signaling of fear, but also point to a double role for the olfactory Grueneberg ganglion in intraspecies as well as interspecies communication of danger.
Abstract: Sensing the chemical warnings present in the environment is essential for species survival. In mammals, this form of danger communication occurs via the release of natural predator scents that can involuntarily warn the prey or by the production of alarm pheromones by the stressed prey alerting its conspecifics. Although we previously identified the olfactory Grueneberg ganglion as the sensory organ through which mammalian alarm pheromones signal a threatening situation, the chemical nature of these cues remains elusive. We here identify, through chemical analysis in combination with a series of physiological and behavioral tests, the chemical structure of a mouse alarm pheromone. To successfully recognize the volatile cues that signal danger, we based our selection on their activation of the mouse olfactory Grueneberg ganglion and the concomitant display of innate fear reactions. Interestingly, we found that the chemical structure of the identified mouse alarm pheromone has similar features as the sulfur-containing volatiles that are released by predating carnivores. Our findings thus not only reveal a chemical Leitmotiv that underlies signaling of fear, but also point to a double role for the olfactory Grueneberg ganglion in intraspecies as well as interspecies communication of danger.

Journal ArticleDOI
TL;DR: Olfactory dysfunction is a serious condition for those affected by it and it deserves more attention from doctors who treat affected patients as well as from scientist who research treatment options.
Abstract: Background The negative consequences of olfactory dysfunction for the quality of life are not widely appreciated and the condition is therefore often ignored or trivialized.

Journal ArticleDOI
TL;DR: A functional dissociation was observed, with central and peripheral mechanisms explaining different aspects of the observed behavioral variance in the olfactory subscores, and data suggest an important role of regional gray matter volume in the right orbitofrontal cortex and Olfactory bulb volume for olf factory performance in healthy individuals.
Abstract: While recent studies suggest an important role of higher order olfactory brain areas for basic olfactory performance, the extent to which cortical and peripheral neural markers account for separate portions of the variability in olfactory perceptual acuity is still unclear. We addressed this question by correlating voxel-based morphometry data from 90 healthy adults with olfactory performance measures. Supplementing this approach with region of interest (ROI) analyses of functionally defined olfactory cortical regions and olfactory bulb volume, we sought to disentangle the relative contribution of central and peripheral areas to behavioral variability. Whole-brain analyses revealed a significant positive correlation of gray matter volume and olfactory function scores in the right orbital sulcus. This effect was confirmed by the ROI analyses, which further indicated a significant association of the olfactory score with olfactory bulb volume. Moreover, a functional dissociation was observed, with central and peripheral mechanisms explaining different aspects of the observed behavioral variance in the olfactory subscores. In line with previous clinical studies, these data thus suggest an important role of regional gray matter volume in the right orbitofrontal cortex and olfactory bulb volume for olfactory performance in healthy individuals.

Journal ArticleDOI
TL;DR: PM-metal neurotoxicity causes brain damage in young urbanites, the olfactory bulb is a target of air pollution and participates in the neuroinflammatory response and since metal concentrations vary significantly in Mexico City urban sub-areas, place of residency has to be integrated with the risk for CNS detrimental effects particularly in children.

Journal ArticleDOI
TL;DR: This review explores the roles of Odorant‐binding proteins, which are still a matter of debate, and finds them good candidates for the transport of inhaled odorants towards the ORs via the nasal mucus.
Abstract: At the periphery of the olfactory system, the binding of odorants on olfactory receptors (ORs) is usually thought to be the first level of the perception of smell. However, at this stage, there is evidence that other molecular mechanisms also interfere with this chemoreception by ORs. These perireceptor events are mainly supported by two groups of proteins present in the olfactory nasal mucus or in the nasal epithelium. Odorant-binding proteins (OBPs), the first group of proteins have been investigated for many years. OBPs are small carrier proteins capable of binding odorants with affinities in the micromolar range. Although there is no absolute evidence to support their functional roles in vertebrates, OBPs are good candidates for the transport of inhaled odorants towards the ORs via the nasal mucus. The second group of proteins involves xenobiotic metabolizing enzymes, which are strongly expressed in the olfactory epithelium and supposed to be involved in odorant transformation, degradation, and/or olfactory signal termination. Following an overview of these proteins, this review explores their roles, which are still a matter of debate. Anat Rec, 296:1333-1345, 2013. © 2013 Wiley Periodicals, Inc.

Journal ArticleDOI
TL;DR: Findings support the concept that cortical olfactory receptors (ORs) and TASRs in the cerebral cortex may have novel physiologic functions that are affected in PD patients.
Abstract: Parkinson disease (PD) is no longer considered a complex motor disorder but rather a systemic disease with variable nonmotor deficits that may include impaired olfaction, depression, mood and sleep disorders, and altered cortical function. Increasing evidence indicates that multiple metabolic defects occur in regions outside the substantia nigra, including the cerebral cortex, even at premotor stages of the disease. We investigated changes in gene expression in the frontal cortex in PD patient brains using a transcriptomics approach. Functional genomics analysis indicated that cortical olfactory receptors (ORs) and taste receptors (TASRs) are altered in PD patients. Olfactory receptors OR2L13, OR1E1, OR2J3, OR52L1, and OR11H1 and taste receptors TAS2R5 and TAS2R50 were downregulated, but TAS2R10 and TAS2R13 were upregulated at premotor and parkinsonian stages in the frontal cortex area 8 in PD patient brains. Furthermore, we present novel evidence that, in addition to the ORs, obligate downstream components of OR function adenylyl cyclase 3 and olfactory G protein (Gαolf), OR transporters, receptor transporter proteins 1 and 2 and receptor expression enhancing protein 1, and OR xenobiotic removing UDP-glucuronosyltransferase 1 family polypeptide A6 are widely expressed in neurons of the cerebral cortex and other regions of the adult human brain. Together, these findings support the concept that ORs and TASRs in the cerebral cortex may have novel physiologic functions that are affected in PD patients.

Journal ArticleDOI
TL;DR: The presumed adaptations observed here follow to a remarkable degree those found in Drosophila sechellia, a specialist upon noni fruit, and suggest a general principle for how specialization affects the sense of smell.
Abstract: Finding appropriate feeding and breeding sites is crucial for all insects. To fulfil this vital task, many insects rely on their sense of smell. Alterations in the habitat—or in lifestyle—should accordingly also be reflected in the olfactory system. Solid functional evidence for direct adaptations in the olfactory system is however scarce. We have, therefore, examined the sense of smell of Drosophila erecta, a close relative of Drosophila melanogaster and specialist on screw pine fruits (Pandanus spp.). In comparison with three sympatric sibling species, D. erecta shows specific alterations in its olfactory system towards detection and processing of a characteristic Pandanus volatile (3-methyl-2butenyl acetate, 3M2BA). We show that D. erecta is more sensitive towards this substance, and that the increased sensitivity derives from a numerical increase of one olfactory sensory neuron (OSN) class. We also show that axons from these OSNs form a complex of enlarged glomeruli in the antennal lobe, the first olfactory brain centre, of D. erecta. Finally, we show that 3M2BA induces oviposition in D. erecta, but not in D. melanogaster. The presumed adaptations observed here follow to a remarkable degree those found in Drosophila sechellia, a specialist upon nonifruit, andsuggest a general principle for how specialization affects the sense of smell.

Journal ArticleDOI
TL;DR: Olfactory dysfunction is common and becomes more common with advancing age, and it is increasingly receiving attention as an important sign for the early diagnosis and the differential diagnosis of neurodegenerative disorders.
Abstract: SUMMARY Background: Disturbances of smell and taste are common. About 5% of the general population have anosmia (absence of the sense of smell). Olfactory dysfunction can markedly impair the quality of life. Methods: Review of pertinent literature retrieved by a selective search. Results: In recent years, simple and reliable tests of the sense of smell have been introduced in otorhinolaryngology. Olfactory testing has become a new focus of attention in neurology as well, mainly because many patients with neurodegenerative diseases—including the majority of those with Parkinson’s or Alzheimer’s disease—have olfactory loss early on in the course of their disorder. Olfactory dysfunction is thus regarded as an early sign of neuro degenerative disease that may allow a tentative diagnosis to be made years before the motor or cognitive disturbances become evident. As for the treatment of olfactory loss, anti-inflammatory drugs and surgery can help in some cases, and olfactory training can lead to significant improvement of post-viral olfactory deficits. Conclusion: Olfactory dysfunction is common and becomes more common with advancing age. It is increasingly receiving attention as an important sign for the early diagnosis and the differential diagnosis of neurodegenerative disorders. ►Cite this as:

Journal ArticleDOI
TL;DR: A physiologically significant role for gene-body 5hmC in transcriptional facilitation and the maintenance of cellular identity independent of its function as an intermediate to demethylation is suggested.
Abstract: The modified DNA base 5-hydroxymethylcytosine (5hmC) is enriched in neurons where it may contribute to gene regulation and cellular identity. To determine how 5hmC influences gene expression in an in vivo neuronal population, we assessed the patterning and function of the base along the developmental lineage of the main olfactory epithelium—from multipotent stem cells through neuronal progenitors to mature olfactory sensory neurons (mOSNs). We find that 5hmC increases over gene bodies during mOSN development with substantial patterning occuring between the progenitor and mOSN stages. Although gene-body 5hmC levels correlate with gene expression in all three developmental cell types, this association is particularly pronounced within mOSNs. Overexpression of Tet3 in mOSNs markedly alters gene-body 5hmC levels and gene expression in a manner consistent with a positive role for 5hmC in transcription. Moreover, Tet3 overexpression disrupts olfactory receptor expression and the targeting of axons to the olfactory bulb, key molecular and anatomical features of the olfactory system. Our results suggest a physiologically significant role for gene-body 5hmC in transcriptional facilitation and the maintenance of cellular identity independent of its function as an intermediate to demethylation.

Journal ArticleDOI
TL;DR: Evidence that some odors can modulate emotion and cognition is described, and the possible implications for the treatment of psychological problems, for example in reducing the effects of stress, are considered.
Abstract: The sense of smell is found widely in the animal kingdom. Human and animal studies show that odor perception is modulated by experience and/or physiological state (such as hunger), and that some odors can arouse emotion, and can lead to the recall of emotional memories. Further, odors can influence psychological and physiological states. Individual odorants are mapped via gene-specified receptors to corresponding glomeruli in the olfactory bulb, which directly projects to the piriform cortex and the amygdala without a thalamic relay. The odors to which a glomerulus responds reflect the chemical structure of the odorant. The piriform cortex and the amygdala both project to the orbitofrontal cortex (OFC) which with the amygdala is involved in emotion and associative learning, and to the entorhinal/hippocampal system which is involved in long-term memory including episodic memory. Evidence that some odors can modulate emotion and cognition is described, and the possible implications for the treatment of psychological problems, for example in reducing the effects of stress, are considered.

Journal ArticleDOI
TL;DR: It is concluded that antennal grooming removes excess native cuticular lipids and foreign chemicals that physically and/or chemically interfere with olfaction, and thus maintains the olfactory acuity of the antennae.
Abstract: Grooming, a common behavior in animals, serves the important function of removing foreign materials from body surfaces. When antennal grooming was prevented in the American cockroach, Periplaneta americana, field emission gun scanning electron microscopy images revealed that an unstructured substance accumulated on nongroomed antennae, covering sensillar pores, but not on groomed antennae of the same individuals. Gas chromatography analysis of antennal extracts showed that over a 24-h period nongroomed antennae accumulated three to four times more cuticular hydrocarbons than groomed antennae. Moreover, nongroomed antennae accumulated significantly more environmental contaminants from surfaces (stearic acid) and from air (geranyl acetate) than groomed antennae. We hypothesized that the accumulation of excess native cuticular hydrocarbons on the antennae would impair olfactory reception. Electroantennogram experiments and single-sensillum recordings supported this hypothesis: antennae that were prevented from being groomed were significantly less responsive than groomed antennae to the sex pheromone component periplanone-B, as well as to the general odorants geranyl acetate and hexanol. We therefore conclude that antennal grooming removes excess native cuticular lipids and foreign chemicals that physically and/or chemically interfere with olfaction, and thus maintains the olfactory acuity of the antennae. Similar experimental manipulations of the German cockroach (Blattella germanica), carpenter ant (Camponotus pennsylvanicus), and the housefly (Musca domestica), which use different modes of antennal grooming, support the hypothesis that antennal grooming serves a similar function in a wide range of insect taxa.

Journal ArticleDOI
TL;DR: This study improves the understanding of the molecular evolution of chemoreceptors in closely related anophelines and suggests possible mechanisms that underlie the behavioral distinctions in host seeking that, in part, account for the differential vectorial capacity of these mosquitoes.
Abstract: Two sibling members of the Anopheles gambiae species complex display notable differences in female blood meal preferences. An. gambiae s.s. has a well-documented preference for feeding upon human hosts, whereas An. quadriannulatus feeds on vertebrate/mammalian hosts, with only opportunistic feeding upon humans. Because mosquito host-seeking behaviors are largely driven by the sensory modality of olfaction, we hypothesized that hallmarks of these divergent host seeking phenotypes will be in evidence within the transcriptome profiles of the antennae, the mosquito’s principal chemosensory appendage. To test this hypothesis, we have sequenced antennal mRNA of non-bloodfed females from each species and observed a number of distinct quantitative and qualitative differences in their chemosensory gene repertoires. In both species, these gene families show higher rates of sequence polymorphisms than the overall rates in their respective transcriptomes, with potentially important divergences between the two species. Moreover, quantitative differences in odorant receptor transcript abundances have been used to model potential distinctions in volatile odor receptivity between the two sibling species of anophelines. This analysis suggests that the anthropophagic behavior of An. gambiae s.s. reflects the differential distribution of olfactory receptors in the antenna, likely resulting from a co-option and refinement of molecular components common to both species. This study improves our understanding of the molecular evolution of chemoreceptors in closely related anophelines and suggests possible mechanisms that underlie the behavioral distinctions in host seeking that, in part, account for the differential vectorial capacity of these mosquitoes.

Journal ArticleDOI
TL;DR: Surprisingly, it is found that TAAR4 is exquisitely sensitive, with apparent affinities for a preferred ligand, phenylethylamine, rivaling those seen with mammalian pheromone receptors.
Abstract: The mammalian main olfactory pathway detects volatile chemicals using two families of G-protein-coupled receptors: a large repertoire of canonical odorant receptors and a much smaller set of trace amine-associated receptors (TAARs). The TAARs are evolutionarily conserved in vertebrates, including humans, suggesting an indispensible role in olfaction. However, little is known about the functional properties of TAARs when expressed in native olfactory sensory neurons. Here we describe experiments using gene targeting, electrophysiology, and optical imaging to study the response properties of TAAR-expressing sensory neurons and their associated glomeruli in mice. We show that olfactory sensory neurons that express a subset of the TAAR repertoire are preferentially responsive to amines. In addition, neurons expressing specific TAARs, TAAR3 or TAAR4, are highly sensitive and are also broadly tuned—responding to structurally diverse amines. Surprisingly, we find that TAAR4 is exquisitely sensitive, with apparent affinities for a preferred ligand, phenylethylamine, rivaling those seen with mammalian pheromone receptors. We provide evidence that this unprecedented sensitivity is mediated via receptor coupling to the canonical odorant transduction cascade. The data suggest that the TAARs are evolutionarily retained in the olfactory receptor repertoire to mediate high-sensitivity detection of a biologically relevant class of odorous stimuli.

Journal ArticleDOI
TL;DR: The present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human Olfactory system.
Abstract: In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system.

Journal ArticleDOI
TL;DR: Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment and older adults who exercise may be able to retain Olfactory function with age.
Abstract: Importance The prevalence of olfactory impairment is high in older adults, and this decline in olfactory ability may pose health and safety risks, affect nutrition, and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objective To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting, and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n = 1611) were ages 53 to 97 years at baseline and were followed for up to 10 years (1998-2010). Main Outcomes and Measures Olfaction was measured with the San Diego Odor Identification Test at 3 examinations (1998-2000, 2003-2005, and 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment 5 (2003-2005) or 10 (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% CI, 25.3%-29.9%) and rates varied by age and sex; those who were older (hazard ratio [HR], 1.88 [95% CI, 1.74-2.03], for every 5 years) or male (HR, 1.27 [95% CI, 1.00-1.61]) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age- and sex-adjusted HR, 0.76 [95% CI, 0.60-0.97]). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment ( P value for trend = .02). Conclusions and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age.

Journal ArticleDOI
TL;DR: It is concluded that the acute Olfactory knowledge acquired through extensive olfactory training leads to the structural reorganization of olfaction brain areas.

Journal ArticleDOI
TL;DR: This study provides an update of normative values for routine clinical use of “Sniffin’ Sticks” in a Turkish population and validates that "Sniffin' Sticks" olfactory test was applicable for clinical usage in aTurkish population.
Abstract: Background: Olfactory assessment is often neglected in clinical practice, although olfactory loss can assist in diagnosis and may lead to significant morbidity. “Sniffin’ Sticks” is a modern test of nasal chemosensory performance that was developed in Germany and validated in many countries. Our aim was to validate the applicability of “Sniffin’ Sticks” in a Turkish population. Material/Methods: The study included 123 healthy volunteers with a reported normal sense of smell and 51 patients complaining of a reduction in their olfactory function presenting either at rhinology or neurology clinics. The mean age of the subjects tested was 30.2±12.5 years in 126 males and 48 females. The participants were divided into 2 groups according to subjective olfactory function – healthy or abnormal. Each subject’s olfactory function was assessed using the “Sniffin’ Sticks” test. Results: We found significant differences in “Sniffin’ Sticks” test results between the abnormal and healthy groups. In healthy subjects, the 10 th percentiles of odor threshold score, odor discrimination score, odor identification score, and TDI score were 7.25, 12, 11, and 32, respectively. Considering the 2 groups together, apple and turpentine were the least well-recognized odors from the 16 odors presented. Conclusions: Our study provides an update of normative values for routine clinical use of “Sniffin’ Sticks” in a Turkish pop ulation. Also, the present study validates that “Sniffin’ Sticks” olfactory test was applicable for clinical usage in a Turkish population.

Journal ArticleDOI
TL;DR: This non-invasive and inexpensive left-right nostril odor detection test appears to be a sensitive and specific test for probable AD.