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Expression of olfactory receptors during development in Xenopus laevis.

A coordinated expression of tissue- and cell-specific genes during development is required to establish the complex functional organization of the vertebrate olfactory system. Owing to the unique features of its olfactory system and the well-characterized phases of its development, Xenopus laevis was chosen as a model organism to study the onset and the temporal and spatial patterns of expression of olfactory-specific genes. Using RT-PCR and in situ hybridization, it was found that expression of Xenopus olfactory marker protein and of class I receptors, which are thought to be responsible for the perception of water-soluble odorants, was detectable as early as stage 32, less than 2 days after fertilization. In contrast, expression of class II receptors, which are thought to recognize airborne odours, was not detected before stage 49, approximately 12 days after fertilization. The results indicate that the expression of olfactory receptors and marker protein is governed by temporally regulated cues during development.

Animals↗

Intranasal concentrations of orally administered flavors.

The odorants emanating from the oral cavity during eating and drinking reach the olfactory mucosa via the pharynx (retronasal olfaction). It is unclear which variables influence the perception of intraorally applied substances. The aim of the present study was to determine the temporal profiles of volatile odor concentrations at different locations in the nasal cavity during consumption of liquid and solid custard samples using proton transfer reaction mass spectrometry. Intranasal odor concentrations were measured at least twice in nine subjects (six female, three male) at four nasal positions during the consumption of liquid and solid custards. The low-viscosity custard was swallowed earlier than the more solid one. The compounds were found to reach the nose in different concentrations. Largest maximal amplitudes were measured in the nasopharynx, whereas lowest concentrations were found in the region of the olfactory cleft. In addition, different odorants reached the different regions in the nasal cavity in varying concentrations, indicated by a significant interaction between factors "position" and "compound". Furthermore, the compounds were found to reach the positions within the nasal cavity with different latencies. These results indicate that different volatile flavor compounds exhibit different temporal and spatial profiles in terms of their intranasal distribution.

Administration, Oral↗

Olfactory deficits in schizophrenia are not a function of task complexity.

The purpose of the current study was to determine if olfactory identification deficits in patients with schizophrenia were related to task complexity. Given that we had previously reported that male patients with schizophrenia are the most impaired on olfactory identification tests (the University of Pennsylvania Smell Identification Test, UPSIT), we wished to determine whether a similar deficit would exist for this group on a task of similar format and complexity, the Colour Identification Test (CIT). Sixty-five neuroleptically medicated patients with a DSM-III-R diagnosis of schizophrenia and 30 normal control subjects participated. The dependent measures were scores on the UPSIT and CIT. Overall, patients with schizophrenia had significantly lower USPIT scores than did the normal control subjects whereas no mean difference was observed for colour identification. Male patients with schizophrenia had olfactory identification deficits but performed comparably to all other groups on the CIT. Furthermore, microsmic patients with schizophrenia had CIT scores that did not differ from normal control subjects. Finally, CIT and UPSIT scores were not significantly correlated for the study sample as a whole. The results of this study suggest that the olfactory identification deficits observed in patients with schizophrenia likely reflect abnormalities of brain areas involved in olfactory pathways and are not a function of task complexity.

Adolescent↗

Olfaction in Drosophila.

The fruit fly, Drosophila melanogaster, is equipped with a sophisticated olfactory sensory system that permits it to recognize and discriminate hundreds of discrete odorants. The perception of these odorants is essential for the animal to identify relevant food sources and suitable sites for egg-laying. Advances in the last year have begun to define the molecular basis of this insect's discriminatory power. The identification of a large multi-gene family of candidate Drosophila odorant receptors suggests that, as in other animals, a multitude of distinct odorants is recognized by a diversity of ligand-binding receptors. How olfactory signals are transduced and interpreted by the brain remains an important question for future analysis. The availability of genetic tools and a complete genome sequence makes Drosophila a particularly attractive organism for studying the molecular basis of olfaction.

Animals↗

Treatment with AC pulsed electromagnetic fields improves olfactory function in Parkinson's disease.

Olfactory dysfunction is a common symptom of Parkinson's disease (PD). It may manifest in the early stages of the disease and infrequently may even antedate the onset of motor symptoms. The cause of olfactory dysfunction in PD remains unknown. Pathological changes characteristic of PD (i.e., Lewy bodies) have been demonstrated in the olfactory bulb which contains a large population of dopaminergic neurons involved in olfactory information processing. Since dopaminergic drugs do not affect olfactory threshold in PD patients, it has been suggested that olfactory dysfunction in these patients is not dependent on dopamine deficiency. I present two fully medicated Parkinsonian patients with long standing history of olfactory dysfunction in whom recovery of smell occurred during therapeutic transcranial application of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density. In both patients improvement of smell during administration of EMFs occurred in conjunction with recurrent episodes of yawning. The temporal association between recovery of smell and yawning behavior is remarkable since yawning is mediated by activation of a subpopulation of striatal and limbic postsynaptic dopamine D2 receptors induced by increased synaptic dopamine release. A high density of dopamine D2 receptors is present in the olfactory bulb and tract. Degeneration of olfactory dopaminergic neurons may lead to upregulation (i.e., supersensitivity) of postsynaptic dopamine D2 receptors. Presumably, small amounts of dopamine released into the synapses of the olfactory bulb during magnetic stimulation may cause activation of these supersensitive receptors resulting in enhanced sense of smell. Interestingly, in both patients enhancement of smell perception occurred only during administration of EMFs of 7 Hz frequency implying that the release of dopamine and activation of dopamine D2 receptors in the olfactory bulb was partly frequency dependent. In fact, weak magnetic fields have been found to cause interaction with biological systems only within narrow frequency ranges (i.e., frequency windows) and the existence of such frequency ranges has been explained on the basis of the cyclotron resonance model.

Aged↗

Menstrual effects on asymmetrical olfactory acuity.

Gender specific discrepancies on psychometric examination are often interpreted to reflect static differences in cerebral hemisphere specialization, but dynamic alterations relating to circulating gonadal hormones may also be relevant after puberty. The often cited inference of a right hemisphere advantage in males and left hemisphere advantage in females derived from small but reliable differences on spatial tasks and verbal tasks, for example, may to some extent relate to gender-specific differences in circulating gonadal hormones. Performance fluctuations on other higher order cognitive tasks through the menstrual cycle tend to support a temporal association between alterations in cerebral laterality and hormone fluctuations. A potential left hemisphere advantage after menstruation when estrogen and progesterone levels are high in contrast to a right hemisphere advantage at menstruation when estrogen and progesterone levels are low has also received support from shifts in visual field perception. The present investigation continues this line of work by measurement of prospective changes in unirhinal olfactory acuity in the menstrual, ovulatory, and midluteal phases of the menstrual cycle in 11 healthy women who agreed to blood assays of estradiol and progesterone prior to completing a modified version of the Connecticut Chemosensory Perception Exam (CCPE). The CCPE detection of n-butanol showed a clear pattern of changes over the menstrual cycle marked by an asymmetry favoring the right nostril during menstruation when estradiol and progesterone levels were low, an asymmetry favoring the left nostril during ovulation when estradiol levels were high and progresterone levels were low, and an absence of asymmetry during the midluteal phase when estradiol levels decreased and progesterone levels increased. Preliminary correlation analyses revealed a potential competitive influence of estradiol and progesterone on this apparent shift in cerebral laterality. There is thus sufficient evidence to conclude that dynamic changes in relative cerebral hemisphere advantages have a temporal relation to fluctuations in circulating gonadal hormones and to suggest the value of additional investigation of more specific causal relations.

Adult↗

Evidence of conscious and subconscious olfactory information processing during word encoding: a magnetoencephalographic (MEG) study.

The present study was meant to distinguish between unconscious and conscious olfactory information processing and to investigate the influence of olfaction on word information processing. Magnetic field changes were recorded in healthy young participants during deep encoding of visually presented words whereby some of the words were randomly associated with an odor. All recorded data were then split into two groups. One group consisted of participants who did not consciously perceive the odor during the whole experiment whereas the other group did report continuous conscious odor perception. The magnetic field changes related to the condition 'words without odor' were subtracted from the magnetic field changes related to the condition 'words with odor' for both groups. First, an odor-induced effect occurred between about 200 and 500 ms after stimulus onset which was similar in both groups. It is interpreted to reflect an activity reduction during word encoding related to the additional olfactory stimulation. Second, a later effect occurred between about 600 and 900 ms after stimulus onset which differed between the two groups. This effect was due to higher brain activity related to the additional olfactory stimulation. It was more pronounced in the group consisting of participants who consciously perceived the odor during the whole experiment as compared to the other group. These results are interpreted as evidence that the later effect is related to conscious odor perception whereas the earlier effect reflects unconscious olfactory information processing. Furthermore, our study provides evidence that only the conscious perception of an odor which is simultaneously presented to the visual presentation of a word reduces its chance to be subsequently recognized.

Adult↗

Olfactory maps and odor images.

The understanding of neuronal processing of olfactory stimuli has been furthered by genetic studies and specialized imaging of particular neuronal populations. Selective optical imaging of odor-induced presynaptic and postsynaptic glomerular activity in the olfactory bulb/antennal lobe has visualized odorant-responsive receptor repertoires and shown a more confined odor image at the level of projection neurons compared to their olfactory receptor neuron input. Genetic tracing of projection neurons connected to particular glomeruli has revealed a somewhat dispersed spatial map of termination areas for these neurons both in insects and in vertebrates. Modifications of the glomerular odor map have resulted in altered percepts of the corresponding odors.

Animals↗

Distinct mechanisms for synchronization and temporal patterning of odor-encoding neural assemblies.

Stimulus-evoked oscillatory synchronization of neural assemblies and temporal patterns of neuronal activity have been observed in many sensory systems, such as the visual and auditory cortices of mammals or the olfactory system of insects. In the locust olfactory system, single odor puffs cause the immediate formation of odor-specific neural assemblies, defined both by their transient synchronized firing and their progressive transformation over the course of a response. The application of an antagonist of ionotropic gamma-aminobutyric acid (GABA) receptors to the first olfactory relay neuropil selectively blocked the fast inhibitory synapse between local and projection neurons. This manipulation abolished the synchronization of the odor-coding neural ensembles but did not affect each neuron's temporal response patterns to odors, even when these patterns contained periods of inhibition. Fast GABA-mediated inhibition, therefore, appears to underlie neuronal synchronization but not response tuning in this olfactory system. The selective desynchronization of stimulus-evoked oscillating neural assemblies in vivo is now possible, enabling direct functional tests of their significance for sensation and perception.

Animals↗

Olfactory/trigeminal interactions in nasal chemoreception.

For a long time, studies devoted to intranasal chemoreception have separately considered the different systems which coexist in the human nasal cavity, especially the olfactory and trigeminal systems. For the former, the findings have contributed to a better understanding of transduction, perception and the treatment of odors. For the latter, data have contributed to the knowledge of somatosensory innervation into the nose, especially in relation to nociception. During the last two decades, an increasing number of studies focused on interactions occurring between both systems. Indeed, most odorant molecules have the propensity to simultaneously stimulate olfactory and trigeminal systems in the nasal cavity. The interactions between both systems appear complex and take place at peripheral, central or perceptual levels. Studies in neurobiology, electrophysiology, psychophysics or functional imaging contribute to determine how both olfactory and trigeminal systems coexist and how one system could influence the other in the treatment of sensory information. However, several structural, functional and methodological questions remain unsolved in the field of olfactory/trigeminal interactions and deserve further research.

Animals↗

Psychologic and neurologic consequences of partial and complete cerebral commissurotomy.

Preliminary psychologic testing was carried out on four patients who had undergone surgical sectioning of a portion or all of the corpus callosum and anterior commissure as a treatment for uncontrollable seizures. Results confirm earlier findings indicating the importance of the forebrain commissures in the interhemispheric exchange of a variety of sensory and motor information, and demonstrate that particular portions of the commissural system are responsible for transferring the information of specific sensory modalities. The patients also showed surprising abilities in performing complex tasks assumed to require integration of information from both hemispheres.

Adolescent↗

Functional expression of olfactory receptors in yeast and development of a bioassay for odorant screening.

The functional expression of olfactory receptors (ORs) is a primary requirement to examine the molecular mechanisms of odorant perception and coding. Functional expression of the rat I7 OR and its trafficking to the plasma membrane was achieved under optimized experimental conditions in the budding yeast Saccharomyces cerevisiae. The membrane expression of the receptor was shown by Western blotting and immunolocalization methods. Moreover, we took advantage of the functional similarities between signal transduction cascades of G protein-coupled receptor in mammalian cells and the pheromone response pathway in yeast to develop a novel biosensor for odorant screening using luciferase as a functional reporter. Yeasts were engineered to coexpress I7 OR and mammalian G(alpha) subunit, to compensate for the lack of endogenous Gpa1 subunit, so that stimulation of the receptor by its ligands activates a MAP kinase signaling pathway and induces luciferase synthesis. The sensitivity of the bioassay was significantly enhanced using mammalian G(olf) compared to the G(alpha15) subunit, resulting in dose-dependent responses of the system. The biosensor was probed with an array of odorants to demonstrate that the yeast-borne I7 OR retains its specificity and selectivity towards ligands. The results are confirmed by functional expression and bioluminescence response of human OR17-40 to its specific ligand, helional. Based on these findings, the bioassay using the luciferase reporter should be amenable to simple, rapid and inexpensive odorant screening of hundreds of ORs to provide insight into olfactory coding mechanisms.

Biological Assay↗

Responsiveness to sucrose affects tactile and olfactory learning in preforaging honey bees of two genetic strains.

Using sucrose solution as reward, we conditioned preforaging honey bees of two genetic strains to tactile stimuli or to odours. Acquisition, extinction of conditioned responses and discrimination between the conditioned stimuli and alternative tactile or olfactory stimuli were measured. Bees of the two genetic strains were selected for their foraging behaviour. In addition, they differ in their responsiveness to sucrose. To analyse the effects of sucrose perception on learning parameters independent of foraging behaviour, we conditioned preforaging bees of the two strains and compared their performance in tactile and olfactory learning paradigms. In both strains, acquisition in tactile and olfactory conditioning is determined by responsiveness to sucrose. There is no genetic effect on the relationship between responsiveness to sucrose and acquisition. Bees responding to low sucrose concentrations perform better than ones that only respond to higher concentrations. Extinction of conditioned responses correlates with acquisition. Responses to alternative stimuli are independent of responsiveness to sucrose.

Animals↗

Functional cloning and reconstitution of vertebrate odorant receptors.

The olfactory systems of vertebrates have a remarkable capacity to recognize and discriminate thousands of different odorant molecules. The initial step in the process of odorant perception is the recognition of volatile odorant molecules by a group of roughly one thousand G protein-coupled odorant receptors that are expressed on the surface of olfactory neuronal cilia. The aims of this study were to obtain functional evidence that these putative odorant receptors recognize and respond to specific odorant molecules, and to elucidate the mechanisms of odorant discrimination in vertebrate olfaction at a receptor level. In order to identify odorant receptors that specifically recognize a particular odorant of interest, we developed a functional cloning strategy in an odorant-directed manner by combining Ca2+-recording and single cell RT-PCR techniques. We then adopted an adenovirus-mediated expression system or a chimeric receptor approach to reconstitute the functionally cloned receptors for further biochemical analyses. We herein describe how we obtained experimental evidence for a combinatory mechanism of odorant recognition by examining the diversity of odorant receptors that recognize a particular odorant of interest, and by determining ligand specificity and structure-function relationships for individual odorant receptors.

Adenoviridae↗

Complexity of olfactory lateralization processes revealed by functional imaging: a review.

Currently available techniques used in neurosciences and particularly cerebral imaging are contributing to a better understanding of human perception and the treatment of sensorial information. In this field, the chemical senses (taste and smell) have received little attention when compared with the auditory, visual and tactile senses. Nevertheless, recent research has been trying to overcome this. Brain regions involved in the processing of olfactory information have been investigated in several studies including a large number dealing with the question of lateralization. However, functional asymmetry in olfaction has still not been resolved and the resulting data have not been homogeneous. In this field, the contribution of cerebral imaging studies is very important insofar as it shows that the processes of functional lateralization in olfaction depend on many factors (nature of stimulus, nature of task, characteristics of subjects ...) that future research will have to consider.

Animals↗

Relation between PROP taster status and fat perception, touch, and olfaction.

We tested the hypothesis that fat perception (sensitivity to and preferences for fat) may be linked to 6-n-propylthiouracil (PROP) taster status as a result of differences in trigeminal innervation of the oral cavity. In addition, we examined the relationship between taster status and sensitivity to other taste attributes, as well as tactile and olfactory sensitivities. Subjects (40 nontasters, 67 medium tasters, and 40 supertasters of PROP) rated samples (potato chips, chocolate drink, mashed potatoes, and vanilla pudding) varying in fat and flavor concentrations for the intensity of fattiness, saltiness, and sweetness, first without and then with nose clips, and for liking. Tactile sensitivity of the tongue was assessed according to responses to stimulation with Von Frey filaments (2.36, 2.44). Olfactory thresholds were determined for two odors (diacetyl and phenylethyl methyl ethyl carbinol). In general, taster status was not related to the perceptions of fat, saltiness, and sweetness. Subjects were able to accurately assess the fat content of the samples. Increasing the flavor levels in the potato chips and mashed potatoes enhanced the perception of fattiness for these systems. Supertasters were more sensitive to stimulation on the median of the tongue with the no. 2.36 Von Frey filament, and the olfactory thresholds for diacetyl were lower for PROP tasters and supertasters than for nontasters.

Adolescent↗

Zinc salts for the treatment of olfactory and gustatory symptoms in psychiatric patients: a case series.

BACKGROUND: Zinc salts have been used extensively in medical settings to treat disorders of gustatory and olfactory function. However, zinc supplements have not been tested in psychiatric patients with smell or taste symptoms. METHOD: The authors examined the effects of zinc supplements on five consecutive patients with symptoms of abnormal taste and smell perception in the context of acute psychiatric illness or treatment. RESULTS: All five patients had complete or partial amelioration of these olfactory and gustatory symptoms after treatment with zinc sulfate or zinc gluconate, apparently independent of the improvement in their underlying psychiatric disorder. CONCLUSION: We recommend treating unusual olfactory and gustatory symptoms with zinc salts, independent of the treatment for the underlying psychiatric disorder.

Antipsychotic Agents↗