Abstract: The olfactory systems of various species solve the challenging problem of general molecular recognition in widely differing ways. Despite this variety, the molecular receptors are invariably G protein-coupled seven-transmembrane proteins, and are encoded by the largest gene families known to exist in a given animal genome. Receptor gene families have been identified in vertebrates and two invertebrate species, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. The complexity of the odorant receptor repertoire is estimated in mouse and rat at 1000 genes, or 1 percent of the genome, surpassing that of the immunoglobulin and T cell receptor genes combined. Two distinct seven-transmembrane gene families may encode in rodents the chemosensory receptors of the vomeronasal organ, which is specialized in the detection of pheromones. Remarkably, these five receptor families have practically no sequence homology among them. Genetic manipulation experiments in mice imply that vertebrate odorant receptors may fulfill a dual role, also serving as address molecules that guide axons of olfactory sensory neurons to their precise target in the brain.

Abstract: Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

Abstract: ▪ Abstract The initial step in olfactory discrimination involves the interaction of odorous ligands with specific receptors on the surface of olfactory sensory neurons. The foundation for a molecular understanding of odor recognition in vertebrates was provided by the identification of a family of genes encoding putative odorant receptors, by Buck & Axel in 1991. Odorant receptor (OR) genes form the largest gene family in the vertebrate genome. This review summarizes progress over the past seven years. Major new insights are: Olfaction is accomplished in vertebrates by a very large number of receptors; olfactory sensory neurons express a small subset of the OR repertoire; in rat and mouse, axons of neurons expressing the same OR converge onto defined glomeruli in the olfactory bulb.

Abstract: Molecular biology studies of olfaction have identified a multigene family of molecular receptors that are likely to be involved in odor transduction mechanisms. However, because previous functional data on peripheral coding were mainly collected from inferior vertebrates, it has been difficult to document the degree of specificity of odor interaction mechanisms. As a matter of fact, studies of the functional expression of olfactory receptors have not demonstrated the low or high specificity of olfactory receptors. In this study, the selectivity of olfactory receptor neurons was investigated in the rat at the cellular level under physiological conditions by unitary extracellular recordings. Individual olfactory receptor neurons were broadly responsive to qualitatively distinct odor compounds. We conclude that peripheral coding is based on activated arrays of olfactory receptor cells with overlapping tuning profiles.

Abstract: Recent progress in understanding the principles and mechanisms in olfaction is the result of multidisciplinary research efforts that explored chemosensation by using a variety of model organisms. Studies on invertebrates, notably nematodes, insects, and crustaceans, to which diverse experimental approaches can be applied, have greatly helped elucidate various aspects of olfactory signaling. From the converging results of genetic, molecular, and physiological studies, a common set of chemosensory mechanisms emerges. Recognition and discrimination of odorants as well as chemo-electrical transduction and processing of olfactory signals appear to be mediated by fundamentally similar mechanisms in phylogenetically diverse animals. The common challenge of organisms to decipher the world of odors was apparently met by a phylogenetically conserved strategy. Thus, comparative studies should continue to provide important contributions toward an understanding of the sense of smell.

Abstract: The primate orbitofrontal cortex is a site of convergence of information from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the orbitofrontal cortex that responds to fat in the mouth. The neurons respond, when fatty foods are being eaten, to pure fat such as glyceryl trioleate and also to substances with a similar texture but different chemical composition such as paraffin oil (hydrocarbon) and silicone oil [Si(CH3)2O)n]. This is evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Some of the population of neurons respond unimodally to the texture of fat. Other single neurons show convergence of taste inputs, and others of olfactory inputs, onto single neurons that respond to fat. For example, neurons were found that responded to the mouth feel of fat and the taste of monosodium glutamate (both found in milk), or to the mouth feel of fat and to odor. Feeding to satiety reduces the responses of these neurons to the fatty food eaten, but the neurons still respond to some other foods that have not been fed to satiety. Thus sensory-specific satiety for fat is represented in the responses of single neurons in the primate orbitofrontal cortex. Fat is an important constituent of food that affects its palatability and nutritional effects. The findings described provide evidence that the reward value (or pleasantness) of the mouth feel of fat is represented in the primate orbitofrontal cortex and that the representation is relevant to appetite.

Abstract: The olfactory organ of an insect is formed by a pair of head appendages, the antennae which carry arrays of innervated hair structures, the sensilla. The antennae are the most important multimodal sensory organs for the insects and their relatives, bearing not only the sensilla of olfaction, but also those of taste, mechano-, hygro-, and thermoreception, and sometimes sensors for CO2. For many insects, the olfactory sense, and therefore the antenna, is of utmost importance not only in their search for food for themselves or their offspring, but for intraspecific communication as well, for example in ants or moths.

Abstract: A small expressed sequence tag (EST) project generating 506 ESTs from 375 cDNAs was undertaken on the antennae of male Manduca sexta moths in an effort to discover olfactory receptor proteins. We encountered several clones that encode apparent transmembrane proteins; however, none is a clear candidate for an olfactory receptor. Instead we found a greater diversity of odourant binding proteins (OBPs) than previously known in moth antennae, raising the number known for M. sexta from three to seven. Together with evidence of seventeen members of the family from the Drosophila melanogaster genome project, our results suggest that insects may have many tens of OBPs expressed in subsets of the chemosensory sensilla on their antennae. These results support a model for insect olfaction in which OBPs selectively transport and present odourants to transmembrane olfactory receptors. We also found five members of a family of shorter proteins, named sensory appendage proteins (SAPs), that might also be involved in odourant transport. This small EST project also revealed several candidate odourant degrading enzymes including three P450 cytochromes, a glutathione S-transferase and a uridine diphosphate (UDP) glucosyltransferase. Several first insect homologues of proteins known from vertebrates, the nematode Caenorhabditis elegans, yeast and bacteria were encountered, and most have now also been detected by the large D. melanogaster EST project. Only thriteen entirely novel proteins were encountered, some of which are likely to be cuticle proteins.

Abstract: Impaired olfaction, hyposmia or anosmia are part of the clinical phenotype in neurodegenerative disorders including Alzheimer’s disease (AD). It has been proposed that the most severely affected areas are interconnected with the central olfactory system in contrast to the relative sparing of other sensory areas which lack olfactory connections. The pathology of the first synaptic relay in the olfactory pathway, the olfactory bulb (OB), has been studied in AD, but the results have been inconsistent. In order to define more fully the pathology of the OB, we analysed 15 AD and 15 control cases, using amyloid and tau immunohistochemistry on serial sections. This study demonstrates for the first time that all layers of the OB are severely affected in AD and in normal ageing. The principal effector cells of the OB, the mitral cells, developed neurofibrillary tangles (NFTs) both in AD and in controls. All the cases, with the exception of two of the controls, contained NFTs. Amyloid immunoreactivity was detected in diffuse, primitive, classical and compact deposits in AD, while five control cases contained mainly diffuse deposits. We did not find a correlation between amyloid deposition and NFT formation. Among the control cases, two contained neither amyloid nor NFTs, eight had NFTs but no amyloid and only five had both NFTs and amyloid. All the AD cases had NFT and amyloid deposition. Our data suggest that the earlier pathology in the OB is NFT formation and more than ten NFTs/section is compatible with 93.3% diagnostic accuracy for AD.

Abstract: Using the training procedure introduced by von Frisch in 1919, we tested the ability of free-flying honeybees to discriminate a conditioning odor from an array of 44 simultaneously presented substances. The stimuli included homologous series of aliphatic alcohols, aldehydes and ketones, isomeric forms of some of these substances, as well as several terpenes and odor mixtures, and thus comprised stimuli of varying degrees of structural similarity to any conditioning odor. We found (i) that the honeybees significantly distinguished between 97.0% of the 1848 odor pairs tested, thus showing an excellent discrimination performance when tested in a free-flying situation with an array of structurally related substances; (ii) a significant negative correlation between discrimination performance and structural similarity of odorants in terms of differences in carbon chain length with all aliphatic substance classes tested; (iii) that both the position and type of a functional group also affected discriminability of odorants in a substance class-specific manner; and (iv) striking similarities in odor structure‐activity relationships between honeybees and human and nonhuman primates tested previously on a subset of substances employed here. Our findings demonstrate that the similiarities found in the structural organization of the olfactory systems of insects and vertebrates are paralleled by striking similarities in relative discrimination abilities. This strongly suggests that similar mechanisms of odor coding and discrimination may underlie olfaction in vertebrates and insects.

Abstract: Olfactory epithelial structure and olfactory bulb neurophysiological responses were measured in chinook salmon and rainbow trout in response to 25 to 300 μg copper (Cu)/L. Using confocal laser scanning microscopy, the number of olfactory receptors was significantly reduced in chinook salmon exposed to ≥0 μg Cu/L and in rainbow trout exposed to ≥200 μg Cu/L for 1 h. The number of receptors was significantly reduced in both species following exposure to 25 μg Cu/L for 4 h. Transmission electron microscopy of olfactory epithelial tissue indicated that the loss of receptors was from cellular necrosis. Olfactory bulb electroencephalogram (EEG) responses to 10−3 M L-serine were initially reduced by all Cu concentrations but were virtually eliminated in chinook salmon exposed to ≥50 μg Cu/L and in rainbow trout exposed to ≥200 μg Cu/L within 1 h of exposure. Following Cu exposure, EEG response recovery rates were slower in fish exposed to higher Cu concentrations. The higher sensitivity of the chinook salmon olfactory system to Cu-induced histological damage and neurophysiological impairment parallels the relative species sensitivity observed in behavioral avoidance experiments. This difference in species sensitivity may reduce the survival and reproductive potential of chinook salmon compared with that of rainbow trout in Cu-contaminated waters.

Abstract: Olfaction involves a dual sensory process for perceiving odors orthonasally (through the nostrils) and retronasally (through the mouth). This investigation entailed developing a measure of sensitivity to an odor delivered in an orally sampled food (orange flavoring in a sucrose-sweetened gelatin) and examining sensitivity in the elderly. In experiment 1, olfactory flavor sensitivity was 49 times lower in elderly (n = 21) than in young (n = 28) subjects. In experiment 2, with 73 elderly women, higher olfactory flavor sensitivity correlated significantly with higher orthonasal perception (Connecticut Chemosensory Clinical Research Center test). Some women, however, exhibited low olfactory flavor sensitivity despite high orthonasal perception; none had high olfactory flavor sensitivity and low orthonasal perception. Those who wore complete or palatal covering dentures had lower olfactory flavor sensitivity than those who were dentate or wore dentures that did not cover the palate. Through multiple regression analysis, orthonasal perception and denture status were found to be independent contributors to predicting olfactory flavor sensitivity. In summary, elderly subjects showed depressed olfactory flavor sensitivity (i.e. retronasal sensitivity) that related to poor orthonasal olfactory perception and denture characteristic. Thus, while good orthonasal olfaction may be necessary for good olfactory flavor sensitivity, it is not sufficient. Other factors, some associated with oral conditions, may impede release and retronasal transport of odors from the mouth to the olfactory receptors.

Abstract: Oscillatory dynamics is a universal design feature of olfactory information-processing systems. Recent results in honeybees and terrestrial slugs suggest that oscillations underlie temporal patterns of olfactory interneuron responses critical for odor discrimination. Additional general design features in olfactory information-processing systems include (1) the use of central processing areas receiving direct olfactory input for odor memory storage and (2) modulation of circuit dynamics and olfactory memory function by nitric oxide. Recent results in the procerebral lobe of the terrestrial slug Limax maximus, an olfactory analyzer with oscillatory dynamics and propagating activity waves, suggest that Lucifer Yellow can be used to reveal a band-shaped group of procerebral neurons involved in the storage of an odor memory. A model has been constructed to relate wave propagation and odor memory bands in the procerebral lobe of L. maximus and to relate these findings to glomerular odor representations in arthropods and vertebrates.

Abstract: The foraging behaviour of bumble bees is well documented for nectar and/or pollen gathering, but little is known about the learning processes underlying such behaviour. We report olfactory conditioning in worker bumble bees Bombus terrestris L. (Hymenoptera: Apidae) obtained under laboratory conditions on restrained individuals. The protocol was adapted from the proboscis extension conditioning previously described in the honey bee Apis mellifera L. Bumble bees were found to be able to learn a pure odorant when it was presented in paired association with a sugar reward, but not when odour and reward were presented in an explicitly unpaired procedure. This suggests an associative basis for this olfactory learning. Bumble bees showed similar conditioning abilities when stimulated with two different floral odours. An effect of the sugar reward concentration on the learning performances was found.

Abstract: Odor sensitivity and identification were examined in normal aging and early Alzheimer's disease (AD). The aims were to investigate AD as associated with lower odor sensitivity, odor identification as a function of retrieval support, and the relationship between global cognitive functioning (Mini-Mental State Exam [MMSE]; M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975) and olfactory performance. Results indicated intact odor sensitivity but deficient odor identification in AD. Both groups benefited from cues in identification, and the size of the gains was equally large in AD patients and controls. The finding of no selective benefit from retrieval support in AD suggests that a degradation of olfactory knowledge contributes to the odor identification deficits in these patients. MMSE and identification were positively related, whereas MMSE and olfactory sensitivity were unrelated. These findings suggest that the AD-related olfactory impairment stems from lesions in cortical rather than peripheral structures.

Abstract: We compared 7 mildly affected Huntington's disease (HD) patients to 7 age- and education-matched healthy controls (NC) on an odor detection test, the California Odor Learning Test, and the California Verbal Learning Test. Results demonstrated that odor detection sensitivity, but not group membership, accounted for significant variance in total olfactory learning. Both groups learned fewer items in the olfactory modality compared to the verbal modality, but retained a similar amount following a delay. No group differences were demonstrated for verbal recognition discriminability, but the HD group demonstrated significantly impaired odor recognition discriminability. Finally, odor detection provided excellent classification sensitivity and specificity between the patients and controls, suggesting that olfactory testing may provide a sensitive measure of the early disease process in HD. (JINS, 1999, 5, 609–615.)

Abstract: Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults and 16 older adults to assess aging effects on the olfactory P3. Amyl acetate was used to elicit the OERPs, with an intertrial interval of 45 s. Young adults produced significantly larger P3 amplitudes and shorter P3 peak latencies than older adults. The olfactory P3 response appears to be sensitive to age-related changes in the olfactory system and may reflect cognitive slowing in the central nervous system.

Abstract: This study examines the effects of a shift in the motivational state (from hunger to satiety) of human neonates on their behavioral and autonomic responsiveness to artificial and food-related odors as a function of stimulus familiarity. In Experiment 1, videotaped facial movements and autonomic (respiration rate: RR, heart rate: HR) responses to five olfactory stimuli (familiar regular formula, unfamiliar regular formula, protein hydrolysate formula, vanillin, control) are recorded in 3-day-old neonates (n = 14) during episodes of irregular sleep. The infants are tested on average 50 min. before and after bottle feeding. RR discriminates the odor stimuli from the control stimulus, indicating clear olfactory detection. Furthermore, neonates react with higher HR change only when exposed to their familiar formula milk during the postprandial condition. The measurement of facial movements with the Baby-Facial Action Coding System indicates that disgust and aversive actions are more often evoked by the odor of regular formulas (familiar or unfamiliar) than by the other olfactory stimuli during the postprandial condition. In Experiment 2, untrained adult observers, presented with the videotapes of the infants' facial responses to the odors, are able to decode differential hedonic signals from the sender faces as a function of the infants' motivational states. The present findings are in line with the concept of olfactory alliesthesia as defined in adults.