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[Structural reconstruction of chemo-sensitive biomembranes during the action of low molecular weight compounds using spin resonance].

Using the spin probe technique, the changes in the supramolecular structure of the central nervous system synaptic membranes and of olfactory hair membranes of Rana temporaria induced by low molecular weight organic substances of different chemical nature, were investigated. It was found that the membrane structures under study differ considerably in their sensitivity to chemical stimulation and in temporal kinetics of structural transitions. A correlation between physiological parameters of olfactory perception of the compounds used and the parameters of structural transitions in olfactory hair membranes was established. The interrelationship between the experimental data and chemoreception of odorants and mediators as well as the applicability of these preparations for membrane screening of biologically active substances are discussed.

Animals↗

Individual differences in odor imaging ability reflect differences in olfactory and emotional perception.

We asked whether the large variability in odor imaging ability is underlain by interindividual differences in the processing of smells and emotion. Olfactory imaging ability, anhedonia level, and odor perception were measured in 40 subjects, using the Vividness of Olfactory Imagery Questionnaire (VOIQ), the Physical Anhedonia Scale, and the European Test of Olfactory Capabilities. "Good" olfactory imagers, defined primarily on the basis of the VOIQ, rated pleasant smells as more familiar and had lower anhedonia scores than "bad" olfactory imagers. Based on self-reported measures, these results suggest that, like olfactory perception, the mental imagery of smells is related to emotion and that, beyond their differences in vividness, good and bad olfactory imagers differ in their experience of emotion and long-term memory of smells.

Adult↗

Spatial coding of enantiomers in the rat olfactory bulb.

Because of their unique properties, enantiomers (pairs of mirror-symmetric, nonsuperimposable molecules that differ only in optical activity and their interaction with other chiral molecules) have been instrumental in demonstrating that olfactory perception relies on molecular shape. To investigate how molecular structure is encoded by the olfactory system, we combined behavioral discrimination tasks with optical imaging of intrinsic signals. We found that rats can behaviorally discriminate members of a wide range of enantiomer pairs, and imaging revealed enantiomer-selective glomeruli in the olfactory bulb, indicating that the spatial pattern of glomerular activity provides sufficient information to discriminate molecular shape.

Animals↗

Trial-by-trial discrimination of three enantiomer pairs by neural ensembles in mammalian olfactory bulb.

Populations of output neurons in the mammalian olfactory bulb (OB) exhibit distinct, widespread spatial and temporal activation patterns when stimulated with odorants. However, questions remain as to how ensembles of mitral/tufted (M/T) neurons in the mammalian OB represent odorant information. In this report, the single-trial encoding limits of random ensembles of putative single- and multiunit M/T cells in the anesthetized rat OB during presentations of enantiomers of limonene, carvone, and 2-butanol are investigated using simultaneous multielectrode recording techniques. The results of these experiments are: the individual constituents of our recorded ensembles broadly represent information about the presented odorants, the ensemble single-trial response of small spatially distributed populations of M/T neurons can readily discriminate between six different odorants, and the most consistent odorant discrimination is attained when the ensemble consists of all available units and their responses are integrated over an entire breathing cycle. These results suggest that small differences in spike counts among the ensemble members become significant when taken within the context of the entire ensemble. This may explain how ensembles of broadly tuned OB neurons contribute to olfactory perception and may explain how small numbers of individual units receiving input from distinct olfactory receptor neurons can be combined to form a robust representation of odorants.

Action Potentials↗

Combined behavioral and c-Fos studies elucidate the vital role of sodium for odor detection.

Salt, known as taste quality, is generally neglected in olfaction, although the olfactory sensory neurons stretch into the salty nasal mucus covering the olfactory epithelium (OE). Using a psychophysical approach, we directly and functionally demonstrate in the awake rat for a variety of structurally diverse odorants that sodium is a critical factor for olfactory perception and sensitivity, both very important components of mammalian communication and sexual behavior. Bathing the olfactory mucus with an iso-osmotic sodium-free buffer solution results in severe deficits in odorant detection. However, sensitivity returns fully within a few hours, indicating continuous mucus production. In the presence of sodium in the mucus covering the OE, all odorants induce odorant-specific c-Fos expression in the olfactory bulb. Yet, if sodium is absent in the mucus, no c-Fos expression is induced as demonstrated for n-octanal. Our noninvasive approach to induce anosmia in mammals here presented--which is fully reversible within hours--opens new possibilities to study the functions of olfactory communication in awake animals.

Acetates↗

A comparison of methods for sniff measurement concurrent with olfactory tasks in humans.

There is a growing appreciation for the role of sniffing in the formation of the olfactory percept. With this in mind, monitoring and measurement of sniffing is an important aspect of olfactory experiments. There are several methods for measuring human sniffs concurrent with odor delivery in olfactory experiments. Here, we set out to compare the temporal sensitivity and power of these different methods by applying them all simultaneously with an olfactory task. We discuss the advantages and disadvantages of each method and conclude in recommending the use of a nasal cannula linked to a pressure sensor whenever possible.

Adolescent↗

Cloning, functional expression and characterization of a human olfactory receptor.

The human olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein on the olfactory neuron cell surface. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed and characterized the first human olfactory receptor (OR 17-40). Application of a mixture of hundred different odorants elicited a transient increase in intracellular calcium at HEK 293-cells which were transfected with a plasmid containing the receptor encoding DNA and a membrane import sequence. By subdividing the odorant mixture in smaller groups we could identify a single component which represented the only effective substance: helional. Testing some structurally closely related molecules we found only one other compound which also could activate the receptor: heliotropyl acetone. All other compounds tested were completely ineffective. These findings represent the beginning of molecular understanding of odorant recognition in humans.

Benzaldehydes↗

Molecular and cellular basis of human olfaction.

The human olfactory systems recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein in the ciliary membrane of olfactory neurons. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed, and characterized some of the human olfactory receptors from chromosome 17. Our results show that a receptor protein is capable of recognizing the particular chemical substructure of an odor molecule and, therefore, is able to respond only to odorants that have a defined molecular structure. These findings represent the beginning of the molecular understanding of odorant recognition in humans. In the future, this knowledge could be used for the design of synthetic ideal receptors for specific odors (biosensors), or the perfect odor molecule for a given receptor.

Humans↗

Receptor diversity and spatial patterning in the mammalian olfactory system.

In order to gain insight into the mechanisms underlying olfactory perception in mammals, we have performed experiments to identify and characterize the basic receptive elements of the olfactory system, the odorant receptors. We have identified a novel multigene family that encodes odorant receptors on olfactory sensory neurons in the nasal cavity. The tremendous size and diversity of this family indicate that perceptual acuity in the olfactory system relies heavily on the differential binding properties of hundreds of different receptor types. In order to determine how the information supplied by such a large collection of diverse receptors might be organized, we have examined the patterns of expression of different odorant receptor genes in the olfactory epithelium. We have observed distinct topographical patterns of odorant receptor RNAs that indicate that the olfactory epithelium is divided into a series of expression zones. These zones are likely to provide for a broad organization of sensory information in the nasal cavity which is maintained in the axonal projection to the olfactory bulb.

Amino Acid Sequence↗

Gene switching and the stability of odorant receptor gene choice.

Individual olfactory sensory neurons express only a single odorant receptor from a large family of genes, and this singularity is an essential feature in models of olfactory perception. We have devised a genetic strategy to examine the stability of receptor choice. We observe that immature olfactory sensory neurons that express a given odorant receptor can switch receptor expression, albeit at low frequency. Neurons that express a mutant receptor gene switch receptor transcription with significantly greater probability, suggesting that the expression of a functional odorant receptor elicits a feedback signal that terminates switching. This process of receptor gene switching assures that a neuron will ultimately express a functional receptor and that the choice of this receptor will remain stable for the life of the cell.

Animals↗

Neural processing at the speed of smell.

Olfaction is typically described as behaviorally slow, suggesting neural processes on the order of hundreds of milliseconds to seconds as candidate mechanisms in the creation of olfactory percepts. Whereas a recent study challenged this view in suggesting that a single sniff was sufficient for optimal olfactory discrimination, a study by Abraham et al. in this issue of Neuron sets out to negate the challenge by demonstrating increased processing time for discrimination of similar versus dissimilar stimuli. Here we reconcile both studies, which in our view together support the notion of a speed-accuracy tradeoff in olfactory discriminations that are made within about 200 ms. These findings are discussed in light of the challenges related to defining olfactory perceptual similarity in nonhuman animals.

Animals↗

Simulation analysis of effects of adrenaline on spike generation in olfactory receptor cells.

Adrenaline is known to affect action potentials induced by the step current injection in an olfactory receptor cell (ORC). It is unclear, however, whether it also modulates action potentials induced by odor stimuli. In the present study, the effects of adrenaline on action potentials in ORCs were investigated quantitatively using a computer simulation. Adrenaline suppressed simulated action potentials induced by step current injection near threshold, and increased spike frequency to strong stimuli by 8-25%. Similar effects were obtained by applying a pseudo-transduction current to a model cell. Surprisingly, adrenaline markedly increased spike frequency to strong stimuli by 30-140%, and increased the slope of the stimulus-response relation compared with that of the step current injection. This suggests that adrenaline enhances odorant contrast in olfactory perception by modulating signal encoding of ORCs.

Action Potentials↗

[Subjective and objectifying olfactometry by means of flow-olfactometer].

BACKGROUND: Is the flow-olfactometer OM2S suitable for subjective and objectifying screening of olfactory function, additional to its use for chemosensory evoked potentials? METHODS: 53 normosmics were challenged prenasally and synchronously with inspiration by two short weak, moderate and strong hydrogen sulfide (H (2)S)- and phenylethyl alcohol (PEA)-stimuli. The subject pressed a button if there was an olfactory perception. The respiratory nasal pressure changes were recorded continuously via a differential pressure transducer. The alterations of breathing pattern during olfactory stimulation were calculated using a custom made LabView software. The interstimulus interval was at least 3 minutes, the respiration had to be regular. RESULTS: The detection-rate (79 - 98 %) was dependent on quality of odor and its concentration during stimulation. H (2)S-stimuli were detected more frequently than PEA-stimuli. The frequency of detection with simultaneous alteration of breathing pattern was independent of quality of odor and strength of odor concentration. 64 % of the subjects detected both weak H (2)S as well as changed synchronously their first poststimulatory breath. CONCLUSION: The H (2)S-detection threshold was estimated both by subjective data and by data of olfactory evoked respiration changes. The flow-olfactometer by Kobal is very well suitable for subjective and respiration-olfactometry, too.

Adult↗

A substructure-based SAR model for odor perception in humans relevant to health risk assessments.

The ability of human to perceive odors is a very complex phenomenon involving the selective binding of molecules to approximately 1000 olfactory receptors. Accordingly, the derivation of a substructure-based SAR model can be expected to be problematic. Yet, based upon published data on odor thresholds of volatile organic chemicals, we were able to derive such an SAR model. An examination of the structural determinants and related modulators indicates that lipophilicity is a major contributor to olfactory perception. The availability of a substructure-based SAR model permits an examination of the relationship between the presence in the environment of odorous chemicals and public health risks.

Environmental Pollutants↗

Olfactory learning.

Unravelling the mechanisms of learning and memory can, and should, be tackled at many levels. Discovery of the huge family of odourant receptor genes provided olfaction with 'molecular' respectability similar to that afforded to the visual system. Consequently, molecular studies have dominated the olfactory literature this past year, even to the point of providing a molecular basis of olfactory perception. Needless to say, the molecular approach favours a 'hard-wired' system; however, other results suggest that flexibility in the olfactory system provides for certain adaptations that are crucial to the biological needs of mammals.

Animals↗

Cortical and medial amygdala are both involved in the formation of olfactory offspring memory in sheep.

Ewes form a selective olfactory memory for their lambs after 2 h of mother-young interaction following parturition. Once this recognition is established, ewes will subsequently reject any strange lamb approaching the udder (i.e. maternal selectivity). The present study tested the functional contribution of different amygdala nuclei to lamb olfactory memory formation. Using the anaesthetic lidocaine, cortical, medial or basolateral nuclei of the amygdala were transiently inactivated during lamb odour memory formation. Reversible inactivation of either cortical or medial amygdala during the first 8 h postpartum impaired lamb olfactory recognition, whereas inactivation of the basolateral nucleus or infusion of artificial cerebrospinal fluid did not. Control experiments indicate that inactivation of the cortical and medial nuclei of the amygdala specifically disrupt memory formation rather than olfactory perception or memory retrieval. These findings show that both nuclei of the amygdala are required for the formation of a lamb olfactory memory and suggest functional interaction between these two nuclei.

Amygdala↗

[Effect of rhythmic and tonic stimulation on the neuronal activity of the olfactory bulb in the newt Triturus cristatus].

Studies have been made of the dependence of neuronal reactions in the olfactory bulb of the newt on the pattern of presentation of a test solution (glutamine 10(-5) M) into the nasal cavity. Responses to stimulation at a frequency 6/min (which corresponds to the minimal rhythm of normal buccal movements) varied in the intensity and sign. The peak of excitation was usually observed after the 2nd or the 3rd stimuli. The increase of stimulation frequency up to 12-24/min increased the number of the inhibitory reactions and the intensity of inhibition. Replacement of rhythmic flow by a constant one results in inhibition of 34% of neurones which reacted by activation to the rhythmic series of 6/min. The data obtained are discussed in relation to the pattern of olfactory perception in newts under natural conditions.

Animals↗

Mucosal activity patterns as a basis for olfactory discrimination: comparing behavior and optical recordings.

In over half a century numerous studies have demonstrated that different odorants produce individually different spatial patterns of neural receptor activity on the olfactory mucosa. However, the thought that these differential activity patterns could be the neural code underlying olfactory perception has not been tested directly. In the present study using operant techniques, rats were trained to differentially identify five odors from a homologous series of iso-intensive straight-chain aldehydes that differed serially by only one carbon atom, viz. hexaldehyde to decaldehyde. The rats identified each of the five odorants with greater than 90% correct identification. The degree of perceptual similarity between any pair of the five odorants was determined. Using multidimensional scaling techniques (MDS) the similarity measures yielded a two-dimensional perceptual odorant space. Optical techniques were used to record the olfactory mucosal activity patterns in response to these same five iso-intensive aldehydes. The mucosal activity elicited by each odorant revealed individually distinct band-like patterns that varied both within and across these bands. More importantly, the relative differential responsivity of the bands was related to chain length. An MDS analysis of the dissimilarity measure between all possible pairs of odorant induced activity patterns yielded a two-dimensional neurophysiologic odorant space. Further analysis indicated that the neurophysiologic and psychophysically determined odorant spaces were highly correlated (F(1,39)=23.9, P=nil). These results give additional credence to the concept that the odorant-induced mucosal activity patterns may serve as the substrate for the perception of odorant quality.

Aldehydes↗