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A study shows that a multi-chromosomal hub assembles in mouse olfactory neurons to ensure that only one odour-sensing receptor is expressed in each neuron -- a feature essential to odour discrimination.A chromosomal hub enables expression of one odour receptor per neuron., Author(s): François SpitzAuthor Affiliations:Chromosomes come together to help mice distinguish odours The expression of vertebrate genes is regulated by activating genomic elements called enhancers. Enhancers can be located far from [...]

For sea turtles, an ability to detect land masses from a considerable distance away, and to distinguish coastal areas from the open sea, might be adaptive. The loggerhead turtle, Caretta caretta, can detect airborne odorants associated with food. To investigate whether sea turtles can also detect odors associated with land, we studied the responses of juvenile loggerheads to odors from coastal mud. Turtles were tested in a water-filled arena in which odorants could be introduced to the air above the water surface. Turtles exposed to air that had passed over a cup containing mud spent more time with their noses out of the water than did control turtles exposed to air that had passed over a cup containing distilled water. The results demonstrate for the first time that loggerheads can detect airborne odorants associated with land, an ability that might play a role in foraging, navigation, or both., Introduction Sea turtles migrate immense distances, sometimes crossing entire ocean basins before returning to their natal region to reproduce (Carr et al. 1978; Bolten 2003; Musick and Limpus 1997). How [...]

Pouched rats can detect Mycobacterium tuberculosis, which causes tuberculosis, in human sputum. Historically, a phosphate-buffered saline solution was added to sputum in the belief that doing so improved rats' detection of M. tuberculosis, but no relevant data were available. Experiment 1 evaluated rats' performance on samples with and without phosphate-buffered saline solution added. There was no difference in detection accuracy. Adding the solution slows sample processing and will not be done in future operational applications. Experiment 2 compared the performance of rats trained on sputum samples with low versus high concentrations of M. tuberculosis. Raining on low-concentration samples improves sensitivity on that sample type. Unfortunately, it is impractical to arrange low-concentration training in the current operational setting, where the rats are used for the second-line screening of samples initially evaluated by microscopy. Key words: African pouched rats, tuberculosis, olfactory discrimination, operant conditioning, Although the goal of applied behavior analysts typically is to improve human behavior, altering animal behavior to benefit participating animals or to benefit humans is also a legitimate part of [...]

A systematic functional analysis across much of the conventional Anopheles gambiae odorant receptor (AgOR) repertoire was carried out in Xenopus oocytes using two-electrode, voltage-clamp electrophysiology. The resulting data indicate that each AgOR manifests a distinct odor-response profile and tuning breadth. The large diversity of tuning responses ranges from AgORs that are responsive to a single or small number of odorants (specialists) to more broadly tuned receptors (generalists). Several AgORs were identified that respond robustly to a range of human volatiles that may play a critical role in anopheline host selection. AgOR responses were analyzed further by constructing a multidimensional odor space representing the relationships between odorants and AgOR responses. Within this space, the distance between odorants is related to both chemical class and concentration and may correlate with olfactory discrimination. This study provides a comprehensive overview of olfactory coding mechanisms of An. gambiae that ultimately may aid in fostering the design and development of olfactory-based strategies for reducing the transmission of malaria and other mosquito-borne diseases. odorant receptor | olfaction doi/10.1073/pnas.0913392107

Olfaction not only plays a key role in the daily life of animals, but also closely relates to neural network plasticity. Our previous behavior studies found that eugenol can improve spatial memory in mice via olfactory inhalation. In the present study, we confirmed this phenomenon by Morris water maze testing and further explored the change of initial expression of olfactory information-odorant receptor gene following eugenol intervention in vivo and in vitro. The results suggested that the effect of eugenol may be mediated by mOR-EG gene expression after olfactory inhalation. Thus, our data may provide an original clue to interpret the action of the holistic therapy-aromatherapy. These studies demonstrated that olfactory signal pathway may be used for an invasive way to intervene in the learning and memory related diseases. Interestingly, our data also showed that an odorant experience might improve the sensitivity of this odorant perception by promoting the specific OR gene expression. Our research provides a new option to elucidate the phenomenon that odorant experience improves olfactory perception. Key words: olfaction, eugenol, spatial memory, aromatherapy, olfactory perception

Olfactory cues of predators, such as feces, are known to elicit antipredator responses in animals (e.g., avoidance, activity). To date, however, there is little information on olfactory predator recognition in primates. We tested whether the odor of feces of different predator categories (historical Malagasy predators and introduced predators) and of Malagasy nonpredators (control) induces antipredator behavior in captive born, predator-naive gray mouse lemurs. In an olfactory predator experiment a mouse lemur was exposed to a particular odor, fixed at a preferred location, where the animal was trained to get a reward. The behavior of the mouse lemur toward the respective stimulus category was videotaped and quantified. Results showed that mouse lemurs avoided the place of odor presentation when the odor belonged to a predator. They reacted with a significantly enhanced activity when exposed to odors of carnivores compared to those of nonpredatory controls. These findings are in favor of a genetic predisposition of olfactory predator recognition that might be based on the perception of metabolites from meat digestion. Keywords: primate, innate, olfaction, feces, antipredator behavior

Two experiments examined item recognition memory for sequentially presented odours. Following a sequence of six odours participants were immediately presented with a series of two-alternative forced-choice (2AFC) test odours. The test pairs were presented in either the same order as learning or the reverse order of learning. Method of testing was either blocked (Experiment 1) or mixed (Experiment 2). Both experiments demonstrated extended recency, with an absence of primacy, for the reverse testing procedure. In contrast, the forward testing procedure revealed a null effect of serial position. The finding of extended recency is inconsistent with the single-item recency predicted by the two-component duplex theory (Phillips & Christie, 1977). We offer an alternative account of the data in which recognition accuracy is better accommodated by the cumulative number of items presented between item learning and item test.

A complete understanding of the mechanisms underlying any kind of sensory, motor or cognitive task requires analysis from the systems to the cellular level. In olfaction, new behavioural evidence in rodents has provided temporal limits on neural processing times that correspond to less than 150 ms--the timescale of a single sniff. Recent in vivo data from the olfactory bulb indicate that, within each sniff, odour representation is not only spatially organized, but also temporally structured by odour-specific patterns of onset latencies. Thus, we propose that the spatial representation of odour is not a static one, but rather evolves across a sniff, whereby for difficult discriminations of similar odours, it is necessary for the olfactory system to 'wait' for later-activated components. Based on such evidence, we have devised a working model to assess further the relevance of such spatiotemporal processes in odour representation.

The nematode Caenorhabditis elegans is present in soils and composts, where it can encounter a variety of microorganisms. Some bacteria in these rich environments are innocuous food sources for C. elegans, whereas others are pathogens. Under laboratory conditions, C. elegans will avoid certain pathogens, such as Serratia marcescens, by exiting a bacterial lawn a few hours after entering it. By combining bacterial genetics and nematode genetics, we show that C. elegans specifically avoids certain strains of Serratia based on their production of the cyclic lipodepsipentapeptide serrawettin W2. Lawn-avoidance behavior is chiefly mediated by the two AWB chemosensory neurons, probably through G protein-coupled chemoreceptors, and also involves the nematode Toll-like receptor gene tol-1. Purified serrawettin W2, added to an Escherichia coil lawn, can directly elicit lawn avoidance in an AWB-dependent fashion, as can another chemical detected by AWB. These findings represent an insight into chemical recognition between these two soil organisms and reveal sensory mechanisms for pathogen recognition in C, elegans. behavior | biosurfactants | host-pathogen interactions | nonribosomal peptide synthetase | olfaction

Many marine fish and invertebrates show a dual life history where settled adults produce dispersing larvae. The planktonic nature of the early larval stages suggests a passive dispersal model where ocean currents would quickly cause panmixis over large spatial scales and prevent isolation of populations, a prerequisite for speciation. However, high biodiversity and species abundance in coral reefs contradict this panmixis hypothesis. Although ocean currents are a major force in larval dispersal, recent studies show far greater retention than predicted by advection models. We investigated the role of animal behavior in retention and homing of coral reef fish larvae resulting in two important discoveries: (i) Settling larvae are capable of olfactory discrimination and prefer the odor of their home reef, thereby demonstrating to us that nearby reefs smell different. (ii) Whereas one species showed panmixis as predicted from our advection model, another species showed significant genetic population substructure suggestive of strong homing. Thus, the smell of reefs could allow larvae to choose currents that return them to reefs in general and natal reefs in particular. As a consequence, reef populations can develop genetic differences that might lead to reproductive isolation. coral reef | olfaction | population genetics

The mammalian odorant receptors (ORs) comprise a large family of G protein-coupled receptors that are critical determinants of both the odorant response profile and the axonal identity of the olfactory sensory neurons in which they are expressed. Although the pathway by which ORs activate odor transduction is well established, the mechanism by which they direct axons into proper glomerular relationships remains unknown. We have developed a gain-of-function approach by using injection of retroviral vectors into the embryonic olfactory epithelium to study the ORs' contribution to axon guidance. By ectopically expressing ORs, we demonstrate that functional OR proteins induce axonal coalescence. Furthermore, ectopic expression of G[alpha] mutants reveals that activation of the signal transduction cascade is sufficient to cause axonal convergence into glomeruli. Analysis of G[alpha] subunit expression indicates that development and odorant transduction use separate transduction pathways. Last, we establish that the generation of cAMP through adenylyl cyclase 3 is necessary to establish proper axonal identity. Our data point to a model in which axonal sorting is accomplished by OR stimulation of cAMP production by coupling to Gas. axon guidance | development | olfaction

A number of electrophysiological experiments have shown that odor exposure alone, unaccompanied by behavioral training, changes the response patterns of neurons in the olfactory bulb. As a consequence of these changes, across mitral cells in the olfactory bulb, individual odors should be better discriminated because of previous exposure. We have previously shown that a daily 2-h exposure to odorants during 2 weeks enhances rats' ability to discriminate between chemically similar odorants. Here, we first show that the perception of test odorants is only modulated by enrichment with odorants that activate at least partially overlapping regions of the olfactory bulb. Second, we show that a broad activation of olfactory bulb neurons by daily local infusion of NMDA into both olfactory bulbs enhances the discrimination between chemically related odorants in a manner similar to the effect of daily exposure to odorants. Computational modeling of the olfactory bulb suggests that activity-dependent plasticity in the olfactory bulb can support the observed modulation in olfactory discrimination capability by enhancing contrast and synchronization in the olfactory bulb. Last, we show that blockade of NMDA receptors in the olfactory bulb impairs the effects of daily enrichment, suggesting that NMDA-dependent plasticity is involved in the changes in olfactory processing observed here. discrimination | enrichment | plasticity

The proboscis is an important head appendage in insects that has primarily been thought to process gustatory information during food intake. Indeed, in Drosophila and other insects in which they have been identified, most gustatory receptors are expressed in proboscis neurons. Our previous characterization of the expression of AgOR7, a highly conserved odorant receptor (OR) of the Afrotropical malaria vector mosquito Anopheles gambiae in the labellum at the tip of the proboscis was suggestive of a potential olfactory function in this mosquito appendage. To test this hypothesis, we used electrophysiological recording and neuronal tracing, and carried out a molecular characterization of candidate OR expression in the labellum of A. gambiae. These studies have uncovered a set of labial olfactory responses to a small spectrum of human-related odorants, such as isovaleric acid, butylamine, and several ketones and oxocarboxylic acids. Molecular analyses indicated that at least 24 conventional OR genes are expressed throughout the proboscis. Furthermore, to more fully examine AgOR expression within this tissue, we characterized the AgOR profile within a single labial olfactory sensillum. This study provides compelling data to support the hypothesis that a cryptic set of olfactory neurons that respond to a small set of odorants are present in the mouth parts of hematophagous mosquitoes. This result is consistent with an important role for the labellum in the close-range discrimination of bloodmeal hosts that directly impacts the ability of A. gambiae to transmit malaria and other diseases. olfaction | proboscis | insect | olfactory receptor neuron

Human olfaction comprises the opposing actions of excitation and inhibition triggered by odorant molecules. In olfactory receptor neurons, odorant molecules not only trigger a G-protein--coupled signaling cascade but also generate various mechanisms to fine tune the odorant-induced current, including a low-selective odorant inhibition of the olfactory signal. This wide-range olfactory inhibition has been suggested to be at the level of ion channels, but definitive evidence is not available. Here, we report that the cyclic nucleotide-gated (CNG) cation channel, which is a key element that converts odorant stimuli into electrical signals, is inhibited by structurally unrelated odorants, consistent with the expression of wide-range olfactory inhibition. Interestingly, the inhibitory effect was small in the homo-oligomeric CNG channel composed only of the principal channel subunit, CNGA2, but became larger in channels consisting of multiple types of subunits. However, even in the channel containing all native subunits, the potency of the suppression on the cloned CNG channel appeared to be smaller than that previously shown in native olfactory neurons. Nonetheless, our results further showed that odorant suppressions are small in native neurons if the subsequent molecular steps mediated by [Ca.sup.2+] are removed. Thus, the present work also suggests that CNG channels switch on and off the olfactory signaling pathway, and that the on and off signals may both be amplified by the subsequent olfactory signaling steps.

Animals readily acquire positive odor-taste hedonic associations, but evidence for this in humans remains weak and was explored further. Retronasal pairing of odors with sucrose or salty stimuli (Experiment 1) increased the rated sweetness of sucrose-paired odors without altering liking, although changes in odor pleasantness correlated with sucrose liking. Experience of odors with sucrose or quinine by sweet likers (Experiment 2) found increased pleasantness and sweetness for sucrose-paired odors, whereas quinine-paired odors became less liked and more bitter. Odor-sucrose pairings in sweet likers and dislikers (Experiment 3) found increased sweetness in both groups but increased odor liking only in likers. These data suggest that evaluative and sensory learning are dissociable and that evaluative changes are sensitive to individual differences in sweet liking. Keywords: olfaction, taste, flavor, evaluative conditioning, hedonics

In sensory neurons of the peripheral nervous system, receptor potentials can be amplified by depolarizing Cl currents. In mammalian olfactory sensory neurons (OSNs), this anion-based signal amplification results from the sequential activation of two distinct types of transduction channels: cAMP-gated Ca channels and Ca-activated Cl channels. The Cl current increases the initial receptor current about 10-fold and leads to the excitation of the neuron. Here we examine the activation mechanism of the Ca-dependent Cl channel. We focus on calmodulin, which is known to mediate Ca effects on various ion channels. We show that the cell line Odora, which is derived from OSN precursor cells in the rat olfactory epithelium, expresses Ca-activated Cl channels. Single-channel conductance, ion selectivity, voltage dependence, sensitivity to niflumic acid, and Ca sensitivity match between Odora channels and OSN channels. Transfection of Odora cells with CaM mutants reduces the Ca sensitivity of the Cl channels. This result points to the participation of calmodulin in the gating process of Ca-ativated Cl channels, and helps to understand how signal amplification works in the olfactory sensory cilia. Calmodulin was previously shown to mediate feedback inhibition of cAMP-synthesis and of the cAMP-gated Ca channels in OSNs. Our results suggest that calmodulin may also be instrumental in the generation of the excitatory Cl current. It appears to play a pivotal role in the peripheral signal processing of olfactory sensory information. Moreover, recent results from other peripheral neurons, as well as from smooth muscle cells, indicate that the calmodulin-controlled, anion-based signal amplification operates in various cell types where it converts Ca signals into membrane depolarization.

The progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. In previous positron emission tomography studies, we found that smelling AND and EST activated regions primarily incorporating the sexually dimorphic nuclei of the anterior hypothalamus, that this activation was differentiated with respect to sex and compound, and that homosexual men processed AND congruently with heterosexual women rather than heterosexual men. These observations indicate involvement of the anterior hypothalamus in physiological processes related to sexual orientation in humans. We expand the information on this issue in the present study by performing identical positron emission tomography experiments on 12 lesbian women. In contrast to heterosexual women, lesbian women processed AND stimuli by the olfactory networks and not the anterior hypothalamus. Furthermore, when smelling EST, they partly shared activation of the anterior hypothalamus with heterosexual men. These data support our previous results about differentiated processing of pheromone-like stimuli in humans and further strengthen the notion of a coupling between hypothalamic neuronal circuits and sexual preferences. hypothalamus | olfaction | positron emission tomography | sexual orientation

The behavioral changes in young mammals is analyzed by Young Turk neuroscientists, if the amygdala, hippocampus, hypothalamus network is damaged. Olfaction varies in human and in nonhuman primates, as despite having amazing human olfactory abilities, humans have a much-atrophied olfactory system compared to other mammals.

Odorants and pheromones as well as sweet- and bitter-tasting small molecules are perceived through activation of G protein-coupled chemosensory receptors. In contrast, gustatory detection of salty and sour tastes may involve direct gating of sodium channels of the DEG/ENaC family by sodium and hydrogen ions, respectively. We have found that ppk25, a Drosophila melano-gastergene encoding a DEG/ENaC channel subunit, is expressed at highest levels in the male appendages responsible for gustatory and olfactory detection of female pheromones: the legs, wings, and antennae. Mutations in the ppk25 gene reduce or even abolish male courtship response to females in the dark, conditions under which detection of female pheromones is an essential courtship-activating sensory input. In contrast, the same mutations have no effect on other behaviors tested. Importantly, ppk25 mutant males that show no response to females in the dark execute all of the normal steps of courtship behavior in the presence of visible light, suggesting that ppk25 is required for activation of courtship behavior by chemosensory perception of female pheromones. Finally, a ppk25 mutant allele predicted to encode a truncated protein has dominant-negative properties, suggesting that the normal Ppk25 protein acts as part of a multiprotein complex. Together, these results indicate that ppk25 is necessary for response to female pheromones by D. melanogaster males, and suggest that members of the DEG/ENaC family of genes play a wider role in chemical senses than previously suspected. courtship | behavior | olfaction | taste

Microbes interfere with the olfactory communication of animals by degrading chemical signals or by adding volatile metabolites. We report on the composition and diversity of the microflora in a sexually selected scent organ, the wing sacs of Saccopteryx bilineata, which are used by males for courting females. Wing sacs lack any glandular tissues. Instead, males clean and refill their wing sacs each day with genital and gular secretions. Females have only a nonfunctional rudiment of this organ. We isolated a total of 40 microbial species with only a moderate overlap in species composition between the sexes. The estimated microbial diversity was significantly lower in males than in females, with a minimum of 52.5 microbial species [+ or -] 5.0 SD in wing sac rudiments of females and 40.3 [+ or -] 4.2 SD in wing sacs of males (jackknife estimates). Males carried on average only 2 out of 40 possible microbial species in their wing sacs. Thus, individual scent profiles of males could originate from individual microflora. The daily routine of wing sac cleaning and refilling has possibly evolved to control microbial scent degradation, to support an individual microflora involved via volatile metabolites in mate choice, or both. Microbes may play a more prominent role in the evolution of morphological structures and behavioral adaptations than previously envisaged. Key words: bacteria, bats, mate choice, microbes, olfactory communication, scent

We develop a mechanistic mathematical model of the G-protein coupled signaling pathway responsible for generating current responses in frog olfactory receptor neurons. The model incorporates descriptions of ligand-receptor interaction, intracellular transduction events involving the second messenger cAMP, effector ion-channel activity, and calcium-mediated feedback steps. We parameterized the model with respect to suction pipette current recordings from single cells stimulated with multiple odor concentrations. The proposed model accurately predicts the receptorcurrent response of the neuron to brief and prolonged odorant exposure and is able to produce the adaptation observed under repeated or sustained stimulation. mathematical model | receptor neuron | olfaction | signal transduction | cilia

Granule cells in the olfactory bulb (OB) are continually produced and added into the neuronal circuit in the adult brain. Sensory input to the OB plays a key role in the survival of newly generated granule cells. Here, we examined in the adult mice whether there is a time window after the generation of new granule cells when their survival is strongly influenced by sensory input. New granule cells were labeled by BrdUrd injection, and the mice were deprived of sensory input unilaterally by naris cauterization. During the initial 14 days after BrdUrd labeling, the number of BrdUrd-positive granule cells was similar for deprived and undeprived OBs. At 28 days or later, the BrdUrd-positive cell number remarkably decreased in the deprived OB. Cauterization at days 14-28 effectively reduced the number of BrdUrd-positive granule cells, whereas 2-week cauterization before or after this period produced little effect. Administration of diazepam, a [GABA.sub.A] receptor modulator, decreased the number of BrdUrd-positive granule cells. The diazepam administration was most effective at days 14-28. Histochemical examination showed that activation of caspase-3 was accompanied by apoptotic cell death of granule cells that was induced by sensory deprivation or diazepam administration. Double labeling with activated caspase-3 and BrdUrd indicated that granule cells at days 14-20 were most susceptible to cell death. These results indicate that there is a critical period when the survival of new granule cells is determined in a sensory experience-dependent manner and that the pharmacological manipulation can mimic the effect of sensory deprivation. neurogenesis | sensory deprivation | apoptosis

Olfaction, which is an important physiological function for the survival of mammals, is controlled by a large multigene family of olfactory receptor (OR) genes. Fishes also have this gene family, but the number of genes is known to be substantially smaller than in mammals. To understand the evolutionary dynamics of OR genes, we conducted a phylogenetic analysis of all functional genes identified from the genome sequences of zebrafish, puffer-fish, frogs, chickens, humans, and mice. The results suggested that the most recent common ancestor between fishes and tetrapods had at least nine ancestral OR genes, and all OR genes identified were classified into nine groups, each of which originated from one ancestral gene. Eight of the nine group genes are still observed in current fish species, whereas only two group genes were found from mammalian genomes, showing that the OR gene family in fishes is much more diverse than in mammals. In mammals, however, one group of genes, [gamma] expanded enormously, containing [approximately equal to] 90% of the entire gene family. Interestingly, the gene groups observed in mammals or birds are nearly absent in fishes. The OR gene repertoire in frogs is as diverse as that in fishes, but the expansion of group [gamma] genes also occurred, indicating that the frog OR gene family has both mammal- and fish-like characters. All of these observations can be explained by the environmental change that organisms have experienced from the time of the common ancestor of all vertebrates to the present. birth-and-death evolution | multigene family | vertebrate evolution

Sensory neurons expressing members of the seven-transmembrane V1r receptor superfamily allow mice to perceive pheromones. These receptors, which exhibit no sequence homology to any known protein except a weak similarity to taste receptors, have only been found in mammals, in the mouse, the V1r repertoire contains >150 members, which are expressed by neurons of the vomeronasal organ, a structure present exclusively in some tetrapod species. Here, we report the existence of a single V1r gene in multiple species of a non-terrestrial, vomeronasal organ-lacking taxon, the teleosts. In zebrafish, this V1r gene is expressed in chemosensory neurons of the olfactory rosette with a punctate distribution, strongly suggesting a role in chemodetection. This unique receptor gene exhibits a remarkably high degree of sequence variability between fish species. It likely corresponds to the original V1r present in the common ancestor of vertebrates, which led to the large and very diverse expansion of vertebrate pheromone receptor repertoires, and suggests the presence of V1rs in multiple nonmammalian phyla. olfaction sensory systems | vomeronasal

Vertebrates aim their noses at regions of interest and sniff in order to acquire olfactory trace signals that carry information on food, reproduction, kinship, danger, etc. Invertebrates likewise position antennae in the surrounding fluid to acquire such signals. Some of the fluid dynamics of these natural sensing processes has been examined piecemeal, but the overall topic of sniffing is not well investigated or understood. It is, however, important for several human purposes, especially sampling schemes for sensors to detect chemical and biological traces in the environment. After establishing some background, a general appraisal is given of nature's accomplishments in the fluid dynamics of sniffing. Opportunities are found for innovation through biomimicry. Since few artificial ('electronic') noses can currently sniff in the natural sense, ways are considered to help them sniff effectively. Security issues such as explosive trace detection, landmine detection, chemical and biological sniffing, and people sampling are examined. Other sniffing applications including medical diagnosis and leak detection are also considered. Several research opportunities are identified in order to advance this topic of biofluid dynamics. Though written from a fluid dynamics perspective, this review is intended for a broad audience. [DOI: 10.1115/1.1891146]

Petromyzonal sulfate and 3 keto-PZS are bile alcohol derivatives that serve as chemoattractants during the life cycle of sea lamprey. The receptors for the migratory and the reproductive pheromones need to be molecularly cloned and characterized in order to understand the molecular biology of olfaction in the sea lamprey.

I present a tentative, and schematic, picture of the olfaction storage system in early mammalians: (i) how the excitation trains from the olfactory bulb excite selectively N types of cells in the piriform cortex and (ii) how these cells transfer their information to a storage area. Simple size and connectivity requirements impose that each odor is stored in a very small duster of [approximately equal to] 3 neurons. This surprising result holds even if the model parameters are strongly altered (e.g., if N = [10.sup.3] rather than [10.sup.2]).

In three experiments with rats, taste + odor interactions in compound aversion conditioning were investigated. In Experiment 1, two odors (0.02% almond and 0.02% orange) were compared on single-element odor aversions, taste (denatonium) potentiated odor aversions, and potentiated odor aversions following taste extinction. Although no odor differences were seen following single-element conditioning, both types of potentiated orange odor aversions were stronger than their almond odor counterparts. These data show that odors of similar conditionability are differentially potentiated by the same taste. To determine whether these differences were due to unique perceptual representations, the effects of elemental extinction or compound extinction on aversions to the compound were investigated in Experiments 2 and 3. In Experiment 2, orange odor extinction weakened responding to the compound significantly more than taste extinction did. In contrast, almond odor extinction and taste extinction produced similar decrements in responding to the compound in Experiment 3. These results suggest that the perceptual representation of these specific taste + odor compounds are different, and they are discussed in regard to configural and within-compound association accounts of potentiation.

The aims of this paper are to describe the rules of the cortical processing of taste and smell, how the pleasantness or affective value of taste and smell are represented in the brain, and to relate this to the brain mechanisms underlying emotion. Much of the fundamental evidence comes from studies in non-human primates, and this is being complemented by functional neuroimaging studies in humans.

Previous research has indicated that volatile odorants are detected through the main olfactory epithefium (MOE), whereas pheromones are detected via the vomeronasal organ (VNO). Gene disruption studies have established that olfactory signaling through the MOE is mediated through receptor stimulation of type 3 adenylyl cyclase (AC3). Mice lacking AC3 cannot detect odorants through the MOE. Recently, it was discovered using olfactory-based behavioral assays that AC3 mutant mice can detect some volatile odorants. An analysis of these mutant mice led to the surprising discovery that some odorants are detected through the VNO. Key words: adenylyl cyclase, olfaction, vomeronasal organ.

The large number of olfactory receptor genes necessitates high throughput methods to analyze their expression patterns. We have therefore designed a high-density oligonucleotide array containing all known mouse olfactory receptor (OR) and V1R vomeronasal receptor genes. This custom array detected a large number of receptor genes, demonstrating specific expression in the olfactory sensory epithelium for [approximately equal to] 800 OR genes previously designated as ORs based solely on genomic sequences. The array also enabled us to monitor the spatial and temporal distribution of gene expression for the entire OR family. Interestingly, OR genes showing spatially segregated expression patterns were also segregated on the chromosomes. This correlation between genomic location and spatial expression provides unique insights about the regulation of this large family of genes.

Glomeruli in the olfactory bulb are anatomically discrete modules receiving input from idiotypic olfactory sensory neurons. To examine the functional organization of sensory inputs to individual glomeruli, we loaded olfactory sensory neurons with a [Ca.sup.2+] indicator and measured odorant-evoked presynaptic [Ca.sup.2+] signals within single glomeruli by using two-photon microscopy in anaesthetized mice. Odorants evoked patterns of discrete [Ca.sup.2+] signals throughout the neuropil of a glomerulus. Across glomeruli, [Ca.sup.2+] signals occurred with equal probability in all glomerular regions. Within single glomeruli, the pattern of intraglomerular [Ca.sup.2+] signals was indistinguishable for stimuli of different duration, identity, and concentration. Moreover, the response time course of the signals was similar throughout the glomerulus. Hence, sensory inputs to individual glomeruli are spatially heterogeneous but seem to be functionally indiscriminate. These results support the view of olfactory glomeruli as functional units in representing sensory information.

The availability of the sequence of the chimpanzee genome provides an opportunity to examine human genes and their chimpanzee orthologs and to analyze selective pressures that have been shaping the olfactory receptor repertoire since the human-chimpanzee divergence. We determined the ratio of nonsynonymous to synonymous changes for each of 186 orthologous pairs and then examined how the distribution of these ratios compares with the distribution expected under neutral drift. Consistent with the diminishing importance of olfaction for these species, we find no evidence for positive selection and we find evidence of weak purifying selection affecting over half of the repertoire.

This study examines University of Pennsylvania Smell Identification Test (UPSIT; R. L. Doty, 1995) performance in 133 controls and 54 chronic, medicated outpatients with schizophrenia (SZ) using item-response theory modeling. Results show that UPSIT items contribute to 1 factor, cover a range of 8 standard errors of measurement, and articulate 3 ability levels. Although it is not difficult enough to discriminate among persons of above-average ability, the test has diagnostic utility in detecting moderate impairment, Independent of item difficulty, 13 items differentiate patients from controls. When 45 patients and 45 controls were matched on gender and age, patient accuracy remained significantly reduced. The findings support the test's utility and demonstrate how traditional data analysis is insensitive to complexities in test performance.

Humans perceive an immense variety of chemicals as having distinct odors. Odor perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs). ORs have diverse protein sequences but can be assigned to subfamilies on the basis of sequence relationships. Members of the same subfamily have related sequences and are likely to recognize structurally related odorants. To gain insight into the mechanisms underlying odor perception, we analyzed the human OR gene family. By searching the human genome database, we identified 339 intact OR genes and 297 OR pseudogenes. Determination of their genomic locations showed that OR genes ate unevenly distributed among 51 different loci on 21 human chromosomes. Sequence comparisons showed that the human OR family is composed of 172 subfamilies. Types of odorant structures that may be recognized by some subfamilies were predicted by identifying subfamilies that contain ORs with known odor ligands or human homologs of such ORs. Analysis of the chromosomal locations of members of each OR subfamily revealed that most subfamilies are encoded by a single chromosomal locus. Moreover, many loci encode only one or a few subfamilies, suggesting that different parts of the genome may, to some extent, be involved in the detection of different types of odorant structural motifs.

In mammals, odor detection in the nose is mediated by a diverse family of olfactory receptors (ORs), which are used combinatorially to detect different odorants and encode their identities. The OR family can be divided into subfamilies whose members are highly related and are likely to recognize structurally related odorants. To gain further insight into the mechanisms underlying odor detection, we analyzed the mouse OR gene family. Exhaustive searches of a mouse genome database identified 913 intact OR genes and 296 OR pseudogenes. These genes were localized to 51 different loci on 17 chromosomes. Sequence comparisons showed that the mouse OR family contains 241 subfamilies. Subfamily sizes vary extensively, suggesting that some classes of odorants may be more easily detected or discriminated than others. Determination of subfamilies that contain ORs with identified ligands allowed tentative functional predictions for 19 subfamilies. Analysis of the chromosomal locations of members of each subfamily showed that many OR gene loci encode only one or a few subfamilies. Furthermore, most subfamilies are encoded by a single locus, suggesting that different loci may encode receptors for different types of odorant structural features. Comparison of human and mouse OR subfamilies showed that the two species have many, but not all, subfamilies in common. However, mouse subfamilies are usually larger than their human counterparts. This finding suggests that humans and mice recognize many of the same odorant structural motifs, but mice may be superior in odor sensitivity and discrimination.

Studies have shown that implanting olfactory ensheathing cells (OECs) may be a promising therapeutic strategy to promote functional recovery after spinal cord injury. Several fundamental questions remain, however, regarding their in vivo interactions in the damaged spinal cord. We have induced a clip compression injury at the T10 level of the spinal cord in adult rats. After a delay of 1 week, OECs isolated from embryonic day 18 rats were implanted into the cystic cavity that had formed at the site of injury. Before implantation, OECs were infected with a LacZ-expressing retrovirus. At 3 weeks after implantation, LacZ-expressing OECs survived the implantation procedure and remained localized to the cystic cavity. At the electron microscopic level, the cystic cavity had clusters of LacZ-expressing OECs and numerous Schwann cells lacking LacZ-expression. Although labeled OECs made no direct contact with axons, unlabeled Schwann cells were associated with either a single myelinated axon or multiple unmyelinated axons. Positively labeled OEC processes often enveloped multiple Schwann cellaxon units. These observations suggest that the role of OECs as the primary mediators of the beneficial effects on axon growth, myelination, and functional recovery after spinal cord injury may require re-evaluation.

In olfactory neurons, expression of a single odorant receptor (OR) from a repertoire of >1,000 genes is required for odor coding and axonal targeting. Here, we demonstrate a role for OR protein as an essential regulator in the establishment of monoallelic OR expression. An OR-promoter-driven reporter expresses in a receptor-like pattern but, unlike a native OR, is coexpressed with an additional OR allele. Expression of a functional OR from the identical promoter eliminates expression of other OR alleles. The presence of an untranslatable OR coding sequence in the mRNA is insufficient to exclude expression of a second OR. Together, these data identify the OR protein as a critical element in a feedback pathway that regulates OR selection.

Previous research indicates the presence of certain odors is associated with enhanced task performance. The present study investigated use of peppermint odor during typing performance, memorization, and alphabetization. Participants completed the protocol twice--once with peppermint odor present and once without. Analysis indicated significant differences in the gross speed, net speed, and accuracy on the typing task, with odor associated with improved performance. Alphabetization also improved significantly under the odor condition but not typing duration or memorization. These results suggest peppermint odor may promote a general arousal of attention, so participants stay focused on their task and increase performance.

Three experiments were conducted to examine how verbal context and sensory stimulation interact to influence odor hedonic perception. Eight common odors were presented in their natural and synthetic forms, and verbal labels designating name and source (natural, synthetic) information were either explicitly given, self-generated, falsely provided, or not provided. Results revealed that verbal information about source influenced hedonic ratings whether or not the odorant itself was also present. When odorants were presented without verbal labels, olfactory evaluations were based in sensation. Name and source information contributed different levels of meaning and influence to perceptual evaluations. The findings are discussed with reference to an experiential-collocation model for odor-label interactions and a dual-coding hypothesis for olfactory perception.

Analysis of the spatiotemporal coupling between neuronal activity and cerebral blood flow requires the precise measurement of the dynamics of RBC flow in individual capillaries that irrigate activated neurons. Here, we use two-photon microscopy in vivo to image individual RBCs in glomerular capillaries in the rat dorsal olfactory bulb. We find that odor stimulation evokes capillary vascular responses that are odorant- and glomerulus-specific. These responses consist of increases as well as decreases in RBC flow, both resulting from independent changes in RBC velocity or linear density. Finally, measuring RBC flow with micrometer spatial resolution and millisecond temporal resolution, we demonstrate that, in olfactory bulb superficial layers, capillary vascular responses precisely outline regions of synaptic activation.

It is shown that comparative genomics, using data from the Anopheles genome project, allows rapid identification of members of three protein classes critical to insect olfaction. A rational design approach similar to that used by the pharmaceutical industry for drug development can then be applied to the development of products that interfere with mosquito olfaction.

At the first stage of processing in the olfactory pathway, the patterns of glomerular activity evoked by different scents are both temporally and spatially dynamic. In the antennal lobe (AL) of some insects, coherent firing of AL projection neurons (PNs) can be phase-locked to network oscillations, and it has been proposed that oscillatory synchronization of PN activity may encode the chemical identity of the olfactory stimulus. It remains unclear, however, how the brain uses this time-constrained mechanism to encode chemical identity when the stimulus itself is unpredictably dynamic. In the olfactory pathway of the moth Manduca sexta, we find that different odorants evoke gamma-band oscillations in the AL and the mushroom body (a higher-order network that receives input from the AL), but oscillations within or between these two processing stages are not temporally coherent. Moreover, the timing of action potential firing in PNs is not phase-locked to oscillations in either the AL or mushroom body, and the correlation between PN synchrony and field oscillations remains low before, during, and after olfactory stimulation. These results demonstrate that olfactory circuits in the moth are specialized to preserve time-varying signals in the insect's olfactory space, and that stimulus dynamics rather than intrinsic oscillations modulate the uniquely coordinated pattern of PN synchronization evoked by each olfactory stimulus. We propose that non-oscillatory synchronization provides an adaptive mechanism by which PN ensembles can encode stimulus identity while concurrently monitoring the unpredictable dynamics in the olfactory signal that typically occur under natural stimulus conditions.

Odorant identity is believed to be encoded in the olfactory bulb (OB) by glomerular activity patterns. It has not yet been possible to visualize and compare entire patterns for different odorants in the same animal because of technical limitations. For this purpose we used high-resolution functional MRI at 7 T, combined with glomerular-layer flat maps, to reveal responses to aliphatic homologues in the mouse OB. These odorants elicited reproducible patterns in the OB, with the medial and lateral regions containing the most intense signals. Unexpectedly, in view of the symmetrical projections of olfactory receptor neurons to medial and lateral glomeruli, the activity patterns in these regions were asymmetrical. The highly activated medial and lateral areas were shared by homologous members, generating a conserved 'family signature' for a homologous series. The moderately active areas, including the dorsal region that has been extensively studied by optical imaging, were more sensitive to the length of the carbon chain, producing more subtle features of individual members and different changing trends among homologues. The global mapping with functional MRI not only extended previous studies but also revealed additional rules for representation of homologues in the OB. Insights into possible relations between the functional patterns, molecular projections, and odor perception may now be obtained based on the global from the olfactory epithelium to the OB glomerular activity patterns.

Odors elicit a well-organized pattern of activation in glomeruli across the surface of the olfactory bulb. However, the mechanisms by which this map is transformed into an odor code by the bulb circuitry remain unclear. Recent physiological studies in bulb slices have identified several synaptic processes that could be involved in sharpening odorant signals. Mitral cells within a single odorant receptor-specific network can be synchronized by dendrodendritic excitatory interactions in a glomerulus, whereas mitral cells in different networks engage in long-lasting lateral inhibition mediated by dendrodendritic synapses with interneurons. The emerging picture is one in which groups of mitral cells use a unique set of mechanisms to accomplish computational functions similar to those performed by analogous modular structures in other sensory systems.