Influence of olfaction on initial weight gain in two genotypes of chicks.
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In this article we discuss five requirements that theoretically must be fulfilled for transnatal chemosensory learning to occur in three placental species, the rat, the sheep, and the human, viz. (1) minimum or partial maturity of nasal chemoreceptor systems, (2) efficient odorivector compounds in the fetal environment, (3) the ability to memorize chemosensory information across birth, (4) perinatal continuity in chemical signals, (5) neonatal ability to detect air-borne odorants previously experienced in the aquatic environment. A substantial body of data is reviewed for the rat, in which fetal chemosensation is now firmly established. The less studied ovine perinate also shows preliminary evidence of nasal chemoreception and of postnatal retention of prenatally experienced odorants. Concerning the human species, we discuss extensive anatomical data supporting nasochemoreception in utero, but as yet no direct or indirect functional demonstration is provided. Furthermore, the strongest evidence of odorivector compounds in amniotic fluid is from human data. The results presented allow generalization of chemosensory functioning in utero in the species considered.
About 1-2% of the human genome is allocated to production of receptors for the olfactory epithelium--a hint as to the possible importance of this chemical sense, which includes two anatomically distinct systems: the main olfactory system with sensory cells located in the upper part of the nasal cavity, and the vomero-nasal organ with sensory cells on the nasal septum. In adults, individual odours may influence mate preferences and a growing body of evidence indicates that naturally occurring odours play an important role in the mediation of the infant's behaviour. Even foetal olfactory learning seems to occur and breast odours from the mother exert a pheromone-like effect at the newborn's first attempt to locate the nipple. Newborns are generally responsive to breast odours produced by lactating women. Olfactory recognition may be implicated in the early stages of the mother-infant attachment process, when the newborns learn to recognize the own mother's unique odour signature--a process possibly facilitated by the high norepinephrine release and the arousal of the locus coeruleus at birth. New knowledge about human odour physiology may have diagnostic and therapeutic implications--the initiation and stabilization of breastfeeding and termination of apnoeic spells are mentioned as examples.
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Osphreiology, though beginning with Aristotle, and the title of a classical monograph from 1819 by Cloquet, has, like the human sense of smell itself, played a relatively modest role, compared to other sensory functions. The anatomical and physiological connections of the nose to the brain proved to be more complex than those of sight, hearing and even touch, and were therefore poorly understood before the second half of the 19th century. Moreover, the close association between smell and taste gave rise to much controversy regarding the respective roles of the first and the fifth cranial nerves. Next, came the unfolding of the evolutionary influence of cerebral structure and function--viz Broca's "limbic" concept, and the "olfactory desert" in the brains of "anosmatic" animals, Jackson's "uncinate" seizures featuring olfactory hallucinations brought the hippocampal formation into focus. Finally, there were the clinical manifestations of hyposmia and hyperosmia, from "coryza", the common cold, to injury or neoplasms causing hyposmia, as well as some endocrine alterations causing hyperosmia. (And let us not forget Charles Huysman's "Against the Grain" and Marcel Proust's evocative fragrant madeleine.).
Kohonen neural networks, also known as Self Organizing Map (SOM), offer a useful 2D representation of the compound distribution inside a large chemical database. This distribution results from the compound organization in a molecular diversity hyperspace derived from a large set of molecular descriptors. Fuzzy techniques based on the "concept of partial truth" reveal to be also a valuable tool for the direct exploitation of chemical databases or SOM. In such cases a fuzzy clustering algorithm is used. In this paper, a complete hybrid system, combining SOM and fuzzy clustering, is applied. As example, a series of olfactory compounds was selected. The complexity of such information is that a same compound may exhibit different odors. It is shown how fuzzy logic helps to have a better understanding of the organization of the compounds. These hybrid systems, using simultaneously SOM and fuzzy clustering, are foreseen as powerful tools for "virtual pre-screening".
To examine the relationship between emotional development and laterality, smells differing in affective valence (predetermined by adults) were presented to 10 neonates. Each infant was presented with two positive and two negative food-related odorants, each paired with a neutral stimulus. Each pair was presented twice, once with the odorant to the right nostril and once to the left nostril. These eight trials were repeated in two blocks. In addition, control trials, where a puff of air was administered to both nostrils, were included. Head turning from midline position to presentation of the odorants as videotaped while the infant slept. Direction of initial head turn served as the dependent measure. A significant interaction with Smell x Nostril x Direction was found. Post hoc analyses revealed that significant effects occurred only for the positive smells. When the positive smells were presented to the left hemisphere, neonates made significantly more head turns towards the smell. This raises the possibility that approach behaviours may develop earlier than withdrawal behaviours.
The gradient of activity produced along the olfactory mucosa by odorant stimulation was measured by the ratio (the LB/MB ratio) of the summated neural discharges recorded from two branches of the olfactory nerve, a lateral branch (LB) supplying a mucosal region near the internal naris and a medial branch (MB) supplying a region near the external naris. Twenty-four frogs "sniffed" sixteen different odorants, each odorant at four concentrations and two flow rates. Increases in concentration and flow rate produced statistically reliable increases in the ratios; the magnitude of these increases was considerably smaller than the magnitude of the statistically significant changes that could be achieved by shifting the odorants themselves. Even the small change due to concentration depended upon the odorant presented. Thus, even at the highest physiologically possible concentrations and flow rates, the general level of the activity gradient along the mucosa appeared to be determined mainly by the particular odorant used. The relative retention time of each of these 16 different odorants was measured in a gas chromatograph fitted with a Carbowax 20M column. In general, the longer the odorant's retention time the smaller its LB/MB ratio. This suggests that the different mucosal gradients of activity are established for different odorants by a chromatographic process. The data further suggest that the mucosa behaves like a polar chromatographic column.
This paper, presented in part as an invited lecture on the occasion of Professor E.P. Köster's retirement from Utrecht University, summarizes a large body of human studies performed at the University of Pennsylvania Smell and Taste Center during the last 17 years. Details of the development of standardized olfactory tests are provided, including their validation and application in a wide variety of clinical and laboratory settings. Included are studies related to transduction mechanisms in olfactory coding and factors that adversely influence olfactory function (e.g. age, gender, smoking, exposure to environmental chemicals, numerous diseases). A brief discussion of the strengths and weaknesses of the olfactory vector hypothesis for neurodegenerative diseases is also presented.
Transduction in chemosensory cells begins with the association of ligand molecules to receptor proteins borne by the cell membrane. The receptor-ligand complexes formed act as signaling compounds that trigger a G-protein cascade. This receptor-ligand interaction, described here by a single-step or double-step reaction, depends on factors controlling the access of the ligand molecules to the cell membrane. Two basic mechanisms can be distinguished: concentration detectors (CD), in which the ligand can freely diffuse to the membrane, and flux detectors (FD), in which it accumulates irreversibly in a distinct perireceptor space where it is chemically deactivated. These two systems, plus their generalization, are investigated and compared. The transient and steady-state numbers of complexes are studied as a function of the external ligand concentration. The biological significance of the results is shown in a well-studied example of FD, the insect sex-pheromone olfactory receptor neuron. How the number of complexes can code for the intensity of stimulation is analyzed using the size, dynamic range and sensitivity of the steady-state responses, and the time needed to reach a predefined level of the transient responses. It is shown that the FD design affords a large increase in sensitivity (a shift of the threshold response towards low concentration) with respect to the CD design, which is paid for by a lesser ability to follow fast changes in stimulus intensity.
It is important to learn about changes in both taste and odor perceptions with increasing age, because the taste of foods we encounter in our daily life is strongly affected by their smell. This study discusses the difference in qualitative taste and odor discrimination between the elderly and the young. Tastants and odorants used in this study were presented not as single stimuli but as a taste mixture (sucrose and tartaric acid) and an odor mixture (beta-phenylethyl alcohol and gamma-undecalactone). The results showed that quality discrimination abilities of the elderly subjects for both taste and odor were significantly lower than those of the young subjects, indicating a decline in quality discrimination abilities related to age. Also, a moderate but significant correlation was observed between the taste discrimination ability and the odor discrimination ability. We measured thresholds for single-taste and odor components in mixtures and compared them between the elderly and the young to investigate the cause for these findings.
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Odor coding in Drosophila is examined at both the cellular and molecular levels. Functional analysis of individual olfactory receptor neurons (ORNs) by single-unit electrophysiology has shown that ORNs divide into discrete classes, with each class exhibiting a characteristic odor response spectrum. Extensive analysis of ORNs in the maxillary palp has revealed six such classes, which are combined in sensilla according to a strict pairing rule. In order to identify the odor receptor genes that determine the odor specificity of these ORN classes, a new algorithm was designed to search DNA databases for proteins with a particular structure, as opposed to a particular sequence. The algorithm identified a large family of genes likely to encode odor receptors. The acj6 gene, originally identified in a screen for mutants defective in olfactory behavior, encodes a transcription factor that regulates a subset of these receptor genes, and is likely to play a critical role in the process by which ORNs select which receptors to express.
Drosophila fruit flies display robust olfactory-driven behaviors with an olfactory system far simpler than that of vertebrates. Endowed with 1300 olfactory receptor neurons, these insects are able to recognize and discriminate between a large number of distinct odorants. Candidate odorant receptor molecules were identified by complimentary approaches of differential cloning and genome analysis. The Drosophila odorant receptor (DOR) genes encode a novel family of proteins with seven predicted membrane-spanning domains, unrelated to vertebrate or nematode chemosensory receptors. There are on the order of 60 or more members of this gene family in the Drosophila genome, far fewer than the hundreds to thousands of receptors found in vertebrates or nematodes. DOR genes are selectively expressed in small subsets of olfactory neurons, in expression domains that are spatially conserved between individuals, bilaterally symmetric and not sexually dimorphic. Double in situ RNA hybridization with a number of pairwise combinations of DOR genes fails to reveal any overlap in gene expression, suggesting that each olfactory neuron expresses one or a small number of receptor genes and is therefore functionally distinct. How is activation of such a subpopulation of olfactory receptor neurons in the periphery sensed by the brain? In the mouse, all neurons expressing a given receptor project with precision to two of 1800 olfactory bulb glomeruli, creating a spatial map of odor quality in the brain. We have employed DOR promoter transgenes that recapitulate expression of endogenous receptor to visualize the projections of individual populations of receptor neurons to subsets of the 43 glomeruli in the Drosophila antennal lobe. The results suggest functional conservation in the logic of olfactory discrimination from insects to mammals.
Polyamines have been implicated in modulation of numerous cell functions. The purpose of this study was to assess the role of polyamines in intracellular regulation of insect antenna. Analysis of study data showed two main findings. First, in vivo treatment with the polyamine synthesis inhibitor alpha-difluoromethyl-ornithine enhanced the sensitivity of male Periplaneta americana antenna to female pheromonal blend. Secondly, polyamine modulated phosphorylation of several antennary proteins including two found exclusively in antenna (30 and 48 kDa). In both of these exclusive antennary proteins, phosphorylation changed after stimulation with the pheromonal blend. These results suggest that polyamines play a regulatory role in detection of female pheromonal blend and that modulation of protein phosphorylation is one of the mechanisms involved in this regulation.
We used the MembStruk first principles computational technique to predict the three-dimensional (3-D) structure of six mouse olfactory receptors (S6, S18, S19, S25, S46 and S50) for which experimental odorant recognition profiles are available for a set of 24 odorants (4-9 carbons aliphatic alcohols, acids, bromo-acids and diacids). We used the HierDock method to scan each predicted OR structure for potential odorant binding site(s) and to calculate binding energies of each odorant in these binding sites. The calculated binding affinity profiles are in good agreement with experimental activation profiles, validating the predicted 3-D structures and the predicted binding sites. For each of the six ORs, the binding site is located between trans-membrane domains (TMs) 3-6, with contributions from extracellular loops 2 and 3. In particular, we find six residue positions in TM3 and TM6 to be consistently involved in the binding modes of the odorants. Indeed, the differences in the experimental recognition profiles can be explained on the basis of these critical residues alone. These predictions are also consistent with mutation data on ligand binding for catecholamine receptors and sequence hypervariability studies for ORs. Based on this analysis, we defined amino acid patterns associated with the recognition of short aliphatic alcohols and mono-acids. Using these two sequence fingerprints to probe the alignment of 869 OR sequences from the mouse genome, we identified 34 OR sequences matching the fingerprint for aliphatic mono-acids and 36 corresponding to the recognition pattern for aliphatic alcohols. We suggest that these two sets of ORs might function as basic arrays for uniquely recognizing aliphatic alcohols and acids. We screened a library of 89 additional molecules against the six ORs and found that this set of ORs is likely to respond to aldehydes and esters with longer carbon chains than their currently known agonists. We also find that compounds associated with the flavor in foods are often among the best calculated binding affinities. This suggests that physiologic ligands for these ORs may be found among aldehydes and esters associated with flavor.
Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (<few days) convert nasal CT scans from an individual patient into an anatomically accurate 3-D numerical nasal model that can be used to predict airflow and odorant transport, which may ultimately determine olfactory sensitivity. The 3-D model can be also be rapidly modified to depict various anatomical deviations, such as polyps and their removal, that may alter nasal airflow and impair olfactory ability. To evaluate the degree to which variations in critical nasal areas such as the olfactory slit and nasal valve can alter airflow and odorant transport, inspiratory and expiratory airflow with odorants were simulated using numerical finite volume methods. Results suggest that anatomical changes in the olfactory region (upper meatus below the cribriform plate) and the nasal valve region will strongly affect airflow patterns and odorant transport through the olfactory region, with subsequent effects on olfactory function. The ability to model odorant transport through individualized models of the nasal passages holds promise for relating anatomical deviations to generalized or selective disturbances in olfactory perception and may provide important guidance for treatments for nasal-sinus disease, occupational rhinitis and surgical interventions that seek to optimize airflow and improve deficient olfactory function.