Abstract: ▪ Abstract Olfaction begins with the transduction of the information carried by odor molecules into electrical signals in sensory neurons. The activation of different subsets of sensory neurons to different degrees is the basis for neural encoding and further processing of the odor information by higher centers in the olfactory pathway. Recent evidence has converged on a set of transduction mechanisms, involving G-protein-coupled second-messenger systems, and neural processing mechanisms, involving modules called glomeruli, that appear to be adapted for the requirements of different species. The evidence is highlighted in this review by focusing on studies in selected vertebrates and in insects and crustaceans among invertebrates. The findings support the hypothesis that olfactory transduction and neural processing in the peripheral olfactory pathway involve basic mechanisms that are universal across most species in most phyla.

Abstract: Electrophysiologic and lesion studies of animals increasingly implicate the amygdala in aspects of emotional processing. Yet, the functions of the human amygdala remain poorly understood. To examine the contributions of the amygdala and other limbic and paralimbic regions to emotional processing, we exposed healthy subjects to aversive olfactory stimuli while measuring regional cerebral blood flow (rCBF) with positron emission tomography. Exposure to a highly aversive odorant produced strong rCBF increases in both amygdalae and in the left orbitofrontal cortex. Exposure to less aversive odorants produced rCBF increases in the orbitofrontal cortex but not in the amygdala. Change of rCBF within the left amygdala and the left OFC was highly intercorrelated, indicating a strong functional interaction between these brain regions. Furthermore, the activity within the left amygdala was associated significantly with subjective ratings of perceived aversiveness. These findings provide evidence that the human amygdala participates in the hedonic or emotional processing of olfactory stimuli.

Abstract: Although cyclic nucleotide-gated channels mediate sensory transduction in olfaction and vision, other forms of sensory transduction are independent of these channels. Caenorhabditis elegans cyclic nucleotide-gated channel mutants respond normally to some olfactory stimuli and to osmotic stimuli, suggesting that these chemosensory responses use an alternative sensory transduction pathway. One gene that may act in this pathway isosm-9, which is required for each of these responses as well as a mechanosensory response to nose touch. osm-9encodes a protein with ankyrin repeats and multiple predicted transmembrane domains that has limited similarity to theDrosophila phototransduction channels transient receptor potential (TRP) and TRP-like (TRPL). The sequence of OSM-9 and other TRP-like genes reveals a previously unsuspected diversity of mammalian and invertebrate genes in this family. osm-9 is required for the activity of the predicted G-protein-coupled odorant receptor ODR-10, which acts in the AWA olfactory neurons; its similarity to other G-protein-regulated transduction channels suggests that OSM-9 is involved in AWA signaling. osm-9:: GFP fusion genes are expressed in a subset of chemosensory, mechanosensory, and osmosensory neurons. osm-9 also affects olfactory adaptation within neurons that require the cyclic nucleotide-gated channel for olfaction; in these neurons, the gene has a regulatory function and not a primary role in sensory transduction.

Abstract: Most animals depend on the identification of odours to locate food or to find mating partners. To accomplish this, the olfactory system must recognize relative concentrations of a large number of substances by analysing complex patterns of chemoreceptor activations1,2, but how these patterns are represented in the brain is not well understood. Previous studies indicated that odours evoke specific patterns of activity in olfactory sensory centres3–7 and led to the hypothesis that single glomeruli in the olfactory bulb of mammals respond to particular receptor types8–10. We made optical recordings in vivo in the honeybee brain to investigate neuronal population responses to odorants delivered naturally to the animal. We report here that odours evoked specific spatio–temporal excitation patterns in the antennal lobe, the structural and functional analogue of the olfactory bulb11. Specific ensembles of active glomeruli represent odours in a combinatorial manner. A comparison between different individuals shows remarkable similarities for a pheromone component, but not for general flower odours. Mixtures evoked patterns that were combinations of the single odorant responses. These combinations were not fully additive, however, indicating inhibitory effects on single glomeruli. Such interactions could be crucial for the formation of singular codes for complex odour blends.

Abstract: Sheep learn to recognize the odours of their lambs within two hours of giving birth, and this learning involves synaptic changes within the olfactory bulb Specifically, mitral cells become increasingly responsive to the learned odour, which stimulates release of both glutamate and GABA (gamma-aminobutyric acid) neurotransmitters from the reciprocal synapses between the excitatory mitral cells and inhibitory granule cells Nitric oxide (NO) has been implicated in synaptic plasticity in other regions of the brain as a result of its modulation of cyclic GMP levels Here we investigate the possible role of NO in olfactory learning We find that the neuronal enzyme nitric oxide synthase (nNOS) is expressed in both mitral and granule cells, whereas the guanylyl cyclase subunits that are required for NO stimulation of cGMP formation are expressed only in mitral cells Immediately after birth, glutamate levels rise, inducing formation of NO and cGMP, which potentiate glutamate release at the mitral-to-granule cell synapses Inhibition of nNOS or guanylyl cyclase activity prevents both the potentiation of glutamate release and formation of the olfactory memory The effects of nNOS inhibition can be reversed by infusion of NO into the olfactory bulb Once memory has formed, however, inhibition of nNOS or guanylyl cyclase activity cannot impair either its recall or the neurochemical release evoked by the learned lamb odour Nitric oxide therefore seems to act as a retrograde and/or intracellular messenger, being released from both mitral and granule cells to potentiate glutamate release from mitral cells by modulating cGMP concentrations We propose that the resulting changes in the functional circuitry of the olfactory bulb underlie the formation of olfactory memories

Abstract: The general features of the olfactory system are remarkably consistent across vertebrates. A phylogenetic analysis of central olfactory projections indicates that at least three distinct olfactory subsystems may be broadly present in vertebrates and that a fourth, the accessory olfactory or vomeronasal system, arose in tetrapods. The origin and function of the vomeronasal system have been the subject of much controversy, but some conclusions can be drawn. The vomeronasal system did not arise as an adaptation to terrestrial life, as indicated by the presence of a vomeronasal system in modern aquatic amphibians and the increasing paleontological evidence that the last common ancestor of amphibians and amniotes was aquatic. The vomeronasal system is involved in both foraging and reproductive behaviors in reptiles and has been shown to be involved in some pheromonally mediated behaviors in mammals. However, among mammals, some pheromonal responses are not mediated by the vomeronasal system, and the possible involvement of the vomeronasal system in other type of behaviors has not yet been investigated. Thus, the relative functions of the olfactory and vomeronasal systems of tetrapods remain unclear. Other hypotheses that features of the olfactory system are specialized for aquatic chemoreception or for pheromone detection are similarly insupportable. For example, the suggestion that members of the olfactory receptor family can be separated into two groups that function for transduction of air-borne or water-borne odorants is contradicted by the presence of both groups in aquatic amphibians and by a phylogenetic analysis of the sequences for these genes. Interestingly, the putative odorant receptors from the vomeronasal epithelium share little sequence similarity with those from the olfactory epithelium, indicating that these receptors may have been independently co-opted from the larger family of seven transmembrane domain receptors for use in odor transduction. A phylogenetic analysis of the distribution of olfactory receptor cell types indicates that microvillar olfactory receptor cells are widespread among vertebrates and are not restricted to aquatic animals or to the vomeronasal epithelium of tetrapods. Previous suggestions that all microvillar receptor cells are specialized for the detection of pheromones are not tenable. Attempts to recognize features of the olfactory system that are common to all vertebrates and might be specialized for the detection of pheromones vs. more general odorants, or for the detection of water-borne vs. air-borne odorants, are not supported by current evidence.

Abstract: PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cin...

Abstract: The application of the grand canonical ensemble in statistical thermodynamics to the stimulus adsorption on the olfactory receptor sites, assuming some simplifying hypotheses, leads us to an expression of the olfactory response R, which is a function of various physico-chemical parameters involved in the olfaction mechanism, e.g. the stimulus concentration, the saturated vapor pressure, the power law exponent and the partition coefficient. This expression of R is in agreement with the olfactory response of the Hill model, but is more explicit. Stevens' law and the olfactory threshold expression are easily deduced from R. The expression of the threshold we established from R enabled us to explain some empirical relations in the literature between the parameters quoted above. The use of the grand canonical ensemble with the chemical potential notion gave us an interpretation of Stevens' law and a better understanding of the role of some parameters involved in the olfaction mechanism, such as saturated vapor pressure and power law exponent.

Abstract: Decrease of olfactory function in patients with Parkinson's disease (PD) has been reported by several authors. The current study investigated olfaction in PD patients using olfactory event-related potentials (OERPs) as an electrophysiologic correlate of olfactory function in combination with psychophysical testing. A specific focus was the influence of antiparkinsonian drugs. We investigated PD patients treated with antiparkinsonian drugs (n = 13) and PD patients who received no pharmacologic treatment (n = 18). They were compared to age- and sex-matched control subjects (n = 38). To obtain OERPs, stimulants were chosen to stimulate specifically the olfactory nerve (2.1 ppm vanillin, 0.8 ppm H2S). In addition, chemosomatosensory event-related potentials were recorded after trigeminal stimulation with 52% v/v CO2. Moreover, the subjects' ability to identify and to discriminate odorants was tested by means of a "squeeze bottle" technique. The study yielded the following major results: (1) Odor identification was impaired in PD patients. It was not influenced by treatment with antiparkinsonian drugs. (2) The OERP latencies were prolonged in both PD patients taking and not taking antiparkinsonian drugs; however, this effect was more pronounced in PD patients taking antiparkinsonian drugs. (3) The intranasal chemosensory trigeminal system seemingly was neither affected by the neuronal degeneration seen in PD nor by treatment with antiparkinsonian drugs.

Abstract: Objective: The authors examined the relationship between deficits in olfactory identification and duration of illness in young and elderly patients with schizophrenia. Method: Olfactory identification performance of 38 patients with schizophrenia and 40 normal subjects was compared by using the University of Pennsylvania Smell Identification Test. Results: The schizophrenic patients demonstrated olfactory deficits relative to the comparison group, and the elderly schizophrenic patients displayed a greater magnitude of olfactory deficit than the younger patients. Independent of normal aging effects and cognitive deficit, patients with schizophrenia showed a strong relationship between olfactory identification scores and duration of illness, which suggests that olfactory abilities decline progressively over the course of the disorder. Conclusions: In contrast to other neuropsychological measures that have been reported to be stable over the course of illness, olfactory identification abilities deteriorate steadily in patients with schizophrenia, even for those with relatively recent onset. (Am J Psychiatry 1997; 154:1016‐1018)

Abstract: Over the last fifteen years, we have witnessed a rapid expansion in the development of artificial odour sensing systems, or so called 'electronic nose' systems. Whilst the power of this approach to flavour analysis has undoubtedly been demonstrated by its recent application to various complex odours, it will be argued that the original research programme, aimed at developing a comparative model of the biological olfactory pathway, has degenerated into an attempt to obtain an ad hoc workable system, based around readily available sensor and pattern recognition (PARC) technologies. At the time, the first 'model' nose system reflected the limited understanding of sensory information processing carried out within the biological olfactory pathway. We are now presented with an opportunity to evaluate and re-assess the architecture for an electronic nose, in view of the recent advances in understanding the key processing principals exploited by the olfactory bulb and cortex in the identification and characterisation of molecular stimuli. In Part I of this paper, the rapid developments in the understanding of the information processing performed by the biological olfactory system are critically reviewed, and its relevance to current research in artificial olfaction is considered. Not only have the initial biochemical pathways involved in the transduction of odour stimuli been uncovered, but also computational models of the key synaptic circuits have advanced to the point where network simulations are clearly capable of odour discrimination. The key processing principles exploited in the olfactory pathway for overcoming operating constraints such as sensor drift/degeneration, limited sensitivity, and xenobiotic response are highlighted, so that their integration into the electronic analogue may be explored in Part II.

Abstract: Odorant-binding proteins (OBPs) are small soluble proteins present in the aqueous medium surrounding olfactory receptor neurons. Their function in olfaction is still unknown: they have been proposed to facilitate the transit of hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to play a role in chemosensory coding. In this study we examine the genomic organization and expression patterns of two o lfactory- s pecific genes ( OS-E and OS-F ) of Drosophila melanogaster , the products of which are members of a protein family in Drosophila sharing sequence similarity with moth OBPs. We show that the OS-E and OS-F transcription units are located <1 kb apart. They are oriented in the same direction and display a similar intron–exon organization. Expression of both OS-E and OS-F proteins is restricted spatially to the ventrolateral region of the Drosophila antenna. Within this region both OS-E and OS-F proteins are expressed within two different types of sensory hairs: in most, if not all, sensilla trichodea and in ∼40% of the interspersed small sensilla basiconica. We consistently observe that OS-E and OS-F are coexpressed, indicating that an individual sensillum can contain more than one odorant-binding protein. The functional significance of the observed expression pattern and its implications for olfactory coding are discussed.

Abstract: (1) Electro-olfactogram recording was used to determine whether the olfactory epithelium of adult sea lamprey is specifically sensitive to bile acids, some of which have been hypothesized to function as pheromones. Ten bile acids were selected from 38 which had already been pre-screened for olfactory activity. These compounds were first tested on their own, then as adapting stimuli, and finally as components of mixtures (2) The lamprey-specific bile acids, petromyzonol sulfate and allocholic acid, were the most potent compounds tested. Five other bile acids were also detectable at picomolar concentrations. Petromyzonol sulfate had a distinctive dose-response curve. (3) Cross-adaptation demonstrated that sensitivity to bile acids is attributable to at least four independent classes of olfactory receptor sites and that both the nature and position of conjugating group(s) are critical to receptor specificity. Notably, petromyzonol sulfate has its own highly specific and independent receptor site. The situation for unconjugated bile acids was more complex and there appeared to be several sub-classes of receptor sites for these compounds. (4) Mixture studies largely confirmed the cross-adaptation results, describing receptor site independence for the same four sets of odorants. Mixture enhancement was also seen when expected and there was no evidence of mixture suppression. (5) Together, these data demonstrate that conspecific bile acids are discriminated by the olfactory epithelium of the sea lamprey, supporting the possibility that these compounds may function as migratory pheromones.

Abstract: Wine is an complex beverage, from a sensory as well as a chemical point of view. Wine can elicit a large number of olfactory responses, in addition to the taste responses of sweet, sour, and bitter, and the oral sensations of astringency, irritation, viscosity, and temperature. The physiology underlying the transduction of these sensory signals is equally complex, and is just beginning to be understood. It is now known that a large number of olfactory receptors are expressed in the olfactory epithelium, with axonal convergence at the glomeruli level in the olfactory bulb. There appear to be at least two antagonistic second-messenger systems utilized in olfactory transduction. Gustation, on the other hand, appears to utilize a variety of transduction mechanisms, including direct ion influx, receptor-dependent and receptor-independent ion channels, and regulation of membrane permeability. Oral sensation represents a third frontier of study; current research indicates that we have yet to develop an effective language for describing the breadth of perceived oral sensations. The implications of differential response for olfactory and gustatory sensory research are briefly discussed.

Abstract: We studied the associative learning capabilities for behaviourally relevant cues in the moth Spodoptera littoralis. The moths were trained to associate a conditioned stimulus (CS), geraniol odour, with an unconditioned stimulus (US), a sucrose solution. The occurrence of a proboscis extension reflex (PER) was tested. The PER performance during acquisition increased steadily with the number of training trials. Non-associative control procedures did not result in learning. PER conditioning was achieved when the CS was presented 1-3 s before the US. A wide range of inter-trial intervals was able to support conditioning. Males and females learned equally well. Moths could to some degree learn the CS-US association after a single trial. These results demonstrate that S. littoralis females and males have a good capability to associate an odour with a reward. The neural basis of olfactory coding in moths has been well studied; thus, the moth provides a powerful system in which to examine the neurobiology of olfactory learning.

Abstract: Chemosensory event-related potentials (CSERP) can be used to examine central nervous odor processing. An important question for understanding odor perception is how different concentrations are processed. In the present study two odors were chosen which activate either the olfactory (linalool) or the trigeminal (menthol) system. Both odors were presented to 11 subjects in four different concentrations. Four subjects had to attend actively to the odors while the others perceived the odors under passive attention. The results showed that increased concentrations of the olfactory stimulus resulted in shorter latencies of the N1 component but did not affect the amplitudes of the CSERP. However, the amplitudes of the stimulus dependent, exogenous components (N1, P2) increased with higher concentrations of the trigeminal stimulus. The amplitude of the late positive complex, which reflects endogenous processes, was usually larger when the odorous stimuli had to be attended to actively. It is concluded that olfactory intensity coding results in a qualitatively different but not in a stronger neuronal response of the human brain.

Abstract: Odor identification ability and detection threshold sensitivity were measured in 25 probands with Huntington's disease, 12 at-risk offspring, and 37 unrelated controls. Relative to controls and at-risk offspring, HD patients exhibited significant impairment on both measures of olfactory function. By contrast, at-risk offspring did not evidence any olfactory impairment relative to controls. Thus, impaired olfactory function does not aggregate in the family members of HD patients, and does not serve as an indicator of genetic vulnerability to the disorder.