Abstract: The mushroom bodies of the Drosophila brain are important for olfactory learning and memory. To investigate the requirement for mushroom body signaling during the different phases of memory processing, we transiently inactivated neurotransmission through this region of the brain by expressing a temperature-sensitive allele of the shibire dynamin guanosine triphosphatase, which is required for synaptic transmission. Inactivation of mushroom body signaling through α/β neurons during different phases of memory processing revealed a requirement for mushroom body signaling during memory retrieval, but not during acquisition or consolidation.

Abstract: Objective To determine whether olfactory loss affects patients' quality of life or level of disability. Design Retrospective survey using questionnaire data and clinic database review. Setting Two university medical center smell and taste clinics. Patients A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). Main Outcome Measures Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. Results Mean (±SD) number of activities of daily living affected by olfactory loss was 4.70 ± 3.56 for the impaired group and 0.61 ± 1.58 for the improved group ( P P P P P P P Conclusions Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.

Abstract: The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans. The strategy of our sequence database mining for full-length, functional candidate odorant receptor genes was based on the high overall sequence similarity and presence of a number of conserved sequence motifs in all known mammalian odorant receptors as well as the absence of introns in their coding sequences. We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors. A new nomenclature for human odorant receptors based on their chromosomal localization and phylogenetic analysis is proposed. We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors. The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction.

Abstract: We identified a large family of putative odorant-binding protein (OBP) genes in the genome of Drosophila melanogaster. Some of these genes are present in large clusters in the genome. Most members are expressed in various taste organs, including gustatory sensilla in the labellum, the pharyngeal labral sense organ, dorsal and ventral cibarial organs, as well as taste bristles located on the wings and tarsi. Some of the gustatory OBPs are expressed exclusively in taste organs, but most are expressed in both olfactory and gustatory sensilla. Multiple binding proteins can be coexpressed in the same gustatory sensillum. Cells in the tarsi that express OBPs are required for normal chemosensation mediated through the leg, as ablation of these cells dramatically reduces the sensitivity of the proboscis extension reflex to sucrose. Finally, we show that OBP genes expressed in the pharyngeal taste sensilla are still expressed in the poxneuro genetic background while OBPs expressed in the labellum are not. These findings support a broad role for members of the OBP family in gustation and olfaction and suggest that poxneuro is required for cell fate determination of labellar but not pharyngeal taste organs.

Abstract: Using the definition that an illusion is observed when a stimulus is invariant but context alters its perception, we examined whether verbal context could produce olfactory illusions. To test this effect, we chose five odors with minimally fixed sources and that could be interpreted with various hedonic connotations. The odors were violet leaf, patchouli, pine oil, menthol, and a 1:1 mixture of isovaleric and butyric acids. Subjects individually sniffed each odor at two different sessions separated by one week. At each session an odor was given a different verbal label (either positive or negative) and subjects rated the odors on several hedonic scales and provided perceptual and interpretative responses to them. Results showed that the perception of an odor could be significantly influenced by the label provided for it. We propose that the cases where verbal labels inverted odor perception are the first empirical demonstrations of olfactory illusions.

Abstract: The sex of individuals plays an important part in determining their olfactory abilities, with females generally being superior to males. The present review examines the way in which sex differences influence sensitivity, identification, familiarity, and recognition of odours. It also examines whether sex differences are more pronounced with some odours than others, and how sex differences are affected by the manner of testing. Two different explanations for the superiority of females over males in olfaction are evaluated.

Abstract: Olfactory dysfunction is a common finding in patients with Parkinson's disease (PD). As most studies reported on odor identification in more advanced and treated PD, we administered an odor detection, discrimination, and identification test to a heterogeneous, partly de novo, group of patients. Forty-one non-demented PD patients, 24 of whom had untreated early PD, and 18 healthy controls, were examined. Odor identification and discrimination data were corrected for odor detection scores. PD patients scored significantly lower on all olfactory tests. Interestingly, the subgroup of de novo patients with early PD also showed significant olfactory disturbances compared with healthy subjects. Within the PD group, using multiple regression analysis, we found a significant, negative correlation between odor discrimination measures and disease The present study is the first to describe decreased performance of PD patients on odor discrimination, in addition to the already well-established deficits in odor detection and identification. Furthermore, odor discrimination measures were related to disease severity, possibly indicating that at least some aspects of olfactory dysfunction in PD may be secondary to ongoing degenerative processes in PD. As significant olfactory impairments were found in early, de novo PD, olfactory tests may be useful in the early diagnosis of PD.

Abstract: Olfaction plays a major role in host preference and blood feeding, integral behaviors for disease transmission by the malaria vector mosquito Anopheles gambiae sensu stricto (henceforth A. gambiae). We have identified four genes encoding candidate odorant receptors from A. gambiae that are selectively expressed in olfactory organs, contain approximately seven transmembrane domains, and show significant similarity to several putative odorant receptors in Drosophila melanogaster. Furthermore, one of the putative A. gambiae odorant receptors exhibits female-specific antennal expression and is down-regulated 12 h after blood feeding, a period during which substantial reduction in olfactory responses to human odorants has been observed. Taken together, these data suggest these genes encode a family of odorant receptors in A. gambiae, whose further study may aid in the design of novel antimalarial programs.

Abstract: Objectives/Hypothesis: Two of the most common causes of olfactory loss include upper respiratory infection (URI) and nasal or sinus disease. The etiology of most URI-related losses is thought to be viral and, as yet, there is no available treatment. In contrast, nasal or sinus disease produces an obstructive or conductive loss that often responds dramatically to appropriate therapy. Therefore, the distinction is important but in many cases may be difficult because such patients often present with no other nasal symptoms, and routine physical findings may be nonspecific. The purpose of this report is to characterize those aspects of the history and physical examination that will help to substantiate the diagnosis of a conductive olfactory loss. Study Design: A retrospective, nonrandomized study of consecutive patients presenting with a primary complaint of olfactory loss. Methods: This study reviewed 428 patients seen at a university-based taste and smell clinic from July 1987 through December 1998. Of this total, 60 patients were determined to have a conductive olfactory loss. All patients were referred specifically because of a primary chemosensory complaint. The University of Pennsylvania Smell Identification Test (UPSIT; Sensonics, Inc., Haddon Heights, NJ) was administered in all cases. Results: The most commonly diagnosed etiologies of olfactory loss were head injury (18%), upper respiratory infection (18%), and nasal or sinus disease (14%). Of the 60 patients with a conductive loss, only 30% complained of nasal obstruction, whereas 58% described a history of chronic sinusitis. Only 45% reported that their olfactory loss at times seemed to fluctuate in severity. Anterior rhinoscopy failed to diagnose pathology in 51% of cases, whereas nasal endoscopy missed the diagnosis in 9%. Systemic steroids elicited a temporary reversal of conductive olfactory loss in 83% of patients who received them, offering a useful diagnostic maneuver, whereas topical steroids did so in only 25%. Conclusions: The etiology for olfactory loss can in many cases be difficult to determine, but it is important to establish prognosis and to predict response to therapy. Diagnosis requires a thorough history, appropriate chemosensory testing, and a physical examination that should include nasal endoscopy. A trial of systemic steroids may serve to verify that the loss is indeed conductive.

Abstract: The sense of smell has been largely ignored by otorhinolaryngologists, even though 1) its medical stewardship falls within their specialty's purview, 2) olfactory dysfunction is not uncommon in the general population, and 3) disorders of olfaction have significant quality of life, nutritional, and safety consequences. This report provides a succinct overview of the major intranasal neural systems present in humans (namely, cranial nerves O, I, and V, and the nonfunctional accessory [vomeronasal] organ system), along with a summary of notable findings resulting from the application of modern olfactory tests to patient populations, emphasizing diseases of the nose. Such tests have led to the discovery of significant influences of age, gender, smoking, toxic exposure, and genetics on the ability to smell. Within the field of otorhinolaryngology, they have revealed that 1) surgical and medical interventions in patients with rhinosinusitis do not, on average, lead to complete recovery of olfactory function, despite common beliefs to the contrary, and 2) associations are generally lacking between measures of airway patency and olfactory function in such cases. These findings have thrown into question the dogma that olfactory loss in rhinosinusitis is attributable primarily to blockage of airflow to the receptors and have led to histopathological studies demonstrating significant olfactory epithelial compromise in sinonasal syndromes.

Abstract: Although nicotine intake clearly reinforces cigarette smoking behavior, non-nicotine smoke stimuli may become conditioned reinforcers of smoking. In Study 1, we compared the acute subjective and reinforcing effects of cigarette smoking in men and women under two conditions: blockade of visual and olfactory/taste smoke stimuli vs. no blockade. Subjective hedonic ratings of 'like puffs' and 'satisfying', but not 'strength', 'high in nicotine', or CO boost, were significantly reduced under the blockade vs. no blockade conditions. During subsequent ad lib puffing, significantly fewer puffs were self-administered under the blockade condition, particularly among women. In Study 2, we examined the influences of these stimuli separately and found that olfactory/taste stimuli, but not visual stimuli, reduced hedonic ratings and puff self-administration in women but not in men. In Study 3, procedures similar to those in Study 1 were used to examine whether this sex difference in responses to conditioned stimuli generalizes to a non-drug consummatory behavior, eating (pizza). However, hedonic ratings and ad lib consumption of pizza were substantially reduced in both men and women following blockade of visual and olfactory/taste food stimuli. These results indicate that the presumably conditioned stimuli of olfactory/taste from cigarette smoke may influence subjective hedonic ratings and reinforcement from smoking more in women than in men. However, this sex difference may not generalize beyond smoking or other drug reinforcement.

Abstract: During food intake flavor perception results from simultaneous stimulation of the gustatory, olfactory and trigeminal systems. Olfactory stimulation occurs mainly through the retronasal pathway and the resulting perception is often interpreted as a taste perception, thus leading to the well-known sensory confusion between taste and olfaction. The present experiment was designed to study, with functional magnetic resonance imaging (fMRI), the cortical representation of olfactory perception in humans in response to retronasal stimulation by odorants delivered in aqueous solution. Psychophysical evaluation confirmed that the stimuli acted as pure olfactory stimuli through the retronasal pathway and did not present any taste component. Results showed activation in all brain regions previously described with neuroimaging techniques using olfactory stimulation with an odorized air flow. Piriform and orbitofrontal cortex were found activated as well as the hippocampal region, the amygdala, the insular lobe, the cingulate gyrus and the cerebellum. These results demonstrate the feasibility of efficiently stimulating the olfactory system in an fMRI scanner through the retronasal pathway with liquids delivered to the oral cavity. The presentation of olfactory stimuli in liquids to the mouth is a realistic model for the study of food-related flavor perception. This stimulation protocol furthermore allows presenting taste and olfactory stimuli separately or combined, thus allowing for direct comparisons between single modality representation, taste or olfaction, and representation of multi-modality mixtures.

Abstract: Extracellular electrophysiological recordings were made from individual type-A trichoid sensilla on the antenna of the female sphinx moth Manduca sexta. A single annulus of the antenna bears about 1,100 of these sensilla, and each is innervated by two olfactory receptor cells. We tested the responses of these receptor cells to a panel of 102 volatile compounds, as well as three plant-derived odor mixtures, and could discern three different functional types of type-A trichoid sensilla. One subset of receptor cells exhibited an apparently narrow molecular receptive range, responding strongly to only one or two terpenoid odorants. The second subset was activated exclusively by aromatics and responded strongly to two to seven odorants. The third subset had a broad molecular receptive range and responded strongly to odorants belonging to several chemical classes. We also found receptor cells that did not respond to any of the odorants tested but were spontaneously active. Certain odorants elicited excitatory responses in some sensilla but inhibitory responses in others, and some receptor cells were strongly excited by certain odorants but inhibited by others. Impregnation of groups of receptor cells in type-A trichoid sensilla with rhodamine-dextran demonstrated that their axons project mainly to the large female glomeruli of the antennal lobe.

Abstract: OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after cont...

Abstract: The mouse's sense of smell is built of approximately 1000 input channels. Each of these consists of a population of olfactory sensory neurons that express the same odorant receptor gene and project their axons to the same targets (glomeruli) in the olfactory bulb. A neuron must choose to express a singular receptor gene from a repertoire of approximately 1000 genes, and its axon must be wired to the corresponding glomerulus, from an array of approximately 1800 glomeruli. Genetic experiments have shown that the expressed odorant receptor specifies axonal choice of the innervated glomerulus, but it is not the only determinant. The mechanisms of odorant receptor gene choice and axonal wiring are central to the functional organization of the mammalian olfactory system. Although principles have emerged, our understanding of these processes is still limited.

Abstract: Summary Most of our current knowledge of olfactory associative learning in Drosophila comes from the behavioral and molecular analysis of mutants that fail to learn. The identities of the genes affected in these mutants implicate new signaling pathways as mediators of associative learning. The expression patterns of these genes provide insight into the neuroanatomical areas that underlie learning. In recent years, there have been great strides in understanding the molecular and neuroanatomical basis for olfaction in insects. It is now clear that much of the association between the conditioned stimuli and the unconditioned stimuli in olfactory learning occurs within mushroom bodies — third order olfactory neurons within the central brain. In this review, we discuss the nature of the behavioral tasks, the molecules, and the neuronal circuits involved in olfactory learning in Drosophila. BioEssays 23:571‐581, 2001. fl 2001 John Wiley & Sons, Inc.

Abstract: Olfactory lamellae of teleosts contain two morphologically different types of olfactory receptor neurons (ORNs): ciliated ORNs (cORNs) and microvillous ORNs (mORNs). However, little is known about the functional difference between these two types of ORNs in fish olfaction. We isolated cORNs and mORNs using a Ca 2+ -free solution method from olfactory organs of the rainbow trout and examined their response characteristics to various odorants including fish pheromone candidates by whole-cell voltage-clamp techniques. Quadruple mixture of amino acids, single amino acids, steroids (analogues of DHP; 17α ,20βdihydroxy-4-pregnen-3-one and ECG; etiocholan-3α -ol-17-one glucuronide), prostaglandins (PGFs) and urine samples collected from immature and mature female fish were applied focally to olfactory cilia or microvilli using a multi-barreled stimulation pipette with a pressure ejection system. Inward current responses to odorants were recorded from both cORNs and mORNs at a holding potential of –60 mV. cORNs responded to the amino acid mixture, single amino acids, urine samples and ECG, whereas mORNs responded specifically either to the amino acid mixture or single amino acids. The response profiles of both cORNs and mORNs to various odorants varied widely. None of cORNs and mORNs responded to fish pheromone candidates, PGFs and DHPs. Androgen treatment of immature fish did not influence olfactory sensitivity of both cORNs and mORNs to the amino acid mixture and both urine samples. Amino acid and bile acid analyses by HPLC showed that both urine samples contained 35 amino acids (1–40 mM) and trace amounts of taurocholic acid and glycoursodeoxycholic acid. Our results suggest that cORNs are ‘generalists’ that respond to a wide variety of odorants, including pheromones, whereas mORNs are ‘specialists’, specific to amino acids, and also suggest that PGFs and DHPs are not pheromones for the rainbow trout.

Abstract: Olfactory receptors in basiconic and grooved-peg sensilla on the antenna of fifth-instar Triatoma infestans nymphs respond to host odours. Gas chromatography analyses of host odour extracts coupled to electrophysiological recordings from basiconic sensillum receptors indicate that nonanal is a constituent of sheep wool and chicken feather odour that stimulates one of the receptors in this type of sensillum. Similar analyses revealed isobutyric acid in rabbit odour to be a chemostimulant for one of the receptors in grooved-peg sensilla. The response of the aldehyde receptor was higher to heptanal, octanal and nonanal than to other aliphatic aldehydes, and the response of the acid receptor was higher to isobutyric acid than to other short-chain branched and unbranched acids. The behavioural responses of fifth-instar T. infestans nymphs to nonanal and isobutyric acid in an air-stream on a servosphere indicate that, whereas nonanal causes activation of the bugs, isobutyric acid induces an increase in upwind displacement, i.e. odour-conditioned anemotaxis. Binary mixtures of these compounds did not improve the attraction obtained with isobutyric acid alone. A comparison of the behavioural and electrophysiological responses of the bugs to different amounts of isobutyric acid in air suggests that attraction is obtained at concentrations that causes low-to-moderate increases in the firing rate of the acid-excited receptor in the grooved-peg sensilla, whereas at a dose that evokes relatively high firing rates (>40 Hz) no attraction is obtained.

Abstract: Deciphering the genome of the fruitfly, Drosophila melanogaster, has revealed 39 genes coding for putative odorant-binding proteins (OBPs), more than are known at present for any other insect species. Using specific antibodies, the expression mosaic of five such OBPs (OS-E, OS-F, LUSH, PBPRP2, PBPRP5) on the antenna and maxillary palp has been mapped in the electron microscope. It was found that (1) OBP expression does correlate with morphological sensillum types and subtypes, (2) several OBPs may be co-localized in the same sensillum, and (3) OBP localization is not restricted to olfactory sensilla. The expression of PBPRP2 in antennal epidermis sheds some light on the possible evolution of OBPs. Microsc. Res. Tech. 55:297–306, 2001. © 2001 Wiley-Liss, Inc.

Abstract: Short-term exposure of the olfactory epithelium of mature male Atlantic salmon parr to either the pesticide simazine (concentrations 1.0 and 2.0 microg l(-1)) or the pesticide atrazine (concentration 1.0 microg l(-1)) significantly reduced the olfactory response to the female priming pheromone, prostaglandin F(2alpha). In addition, the reproductive priming effect of the pheromone on the levels of expressible milt was also reduced after exposure to the individual pesticides (simazine 0.1, 0.5, 1.0 and 2.0 microg l(-1) and atrazine 0.5 and 2.0 microg l(-1)). When the olfactory epithelium was exposed to a mixture of simazine and atrazine, (concentrations of 0.5:0.5 and 1.0:1.0 microg l(-1)), there was no significant reduction in the olfactory response when compared to the single pesticides at equivalent concentrations. In addition, exposure to a mixture of simazine and atrazine had no synergistic effect on the priming response, and plasma levels of testosterone, 11-ketotestosterone and 17,20beta-dihydroxy-4-pregnen-3-one were similar in the groups of male parr exposed to the individual pesticides. Although the levels of expressible milt were reduced in all groups, there were no significant differences between the different pesticide treatments. The results of the study suggest that the two s-triazine pesticides have an additive and not a synergistic impact on olfactory-mediated endocrine function in mature male salmon parr.

Abstract: Several studies indicate that women outperform men in olfactory identification tasks. The psychophysical data are more divergent when it comes to gender differences at levels of odor processing which are cognitively less demanding. We therefore compared cerebral activation with H2(15)O PET in 12 females and 11 males during birhinal passive smelling of odors and odorless air. The odorous compounds (odorants) were pure olfactory, or mixed olfactory and weakly trigeminal. Using odorless air as the baseline condition, activations were found bilaterally in the amygdala, piriform and insular cortices in both sexes, irrespective of the odor. No gender difference was detected in the pattern of cerebral activation (random effect analysis SPM99, corrected p < 0.05) or in the subjective perception of odors. Males and females seem to use similar cerebral circuits during the passive perception of odors. The reported female superiority in assessing olfactory information including odor identification is probably an effect of a difference at a cognitive, rather than perceptive level of olfactory processing.

Abstract: Calcium (Ca2+) influx through Ca2+-permeable ion channels plays a pivotal role in a variety of neuronal signaling processes, and negative-feedback control of this influx by Ca2+ itself is often equally important for modulation of such signaling. Negative modulation by Ca2+ through calmodulin (CaM) on cyclic nucleotide-gated (CNG) channels underlies the adaptation of olfactory receptor neurons to odorants. We show that this feedback requires two additional subunits of the native olfactory channel, CNGA4 and CNGB1b, even though the machinery for CaM binding and modulation is present in the principal subunit CNGA2. This provides a rationale for the presence of three distinct subunits in the native olfactory channel and underscores the subtle link between the molecular make-up of an ion channel and the physiological function it subserves.

Abstract: To identify potential hormonal pheromones of the round goby (Neogobius melanostomus), a species recently introduced to the Great Lakes, we used electro-olfactogram (EOG) recording to examine olfactory responsiveness to more than 100 steroids and prostaglandins. Neogobius detected free and conjugated 18-, 19and 21-carbon steroids, but did not detect prostaglandins. EOG cross-adaptation, used to determine if Neogobius can discriminate the detected compounds at the sensory level, suggested that the detected steroids act on four classes of olfactory receptor mechanisms named (according to the most potent ligand for each): estrone, 17β-estradiol-3β-glucuronide, etiocholanolone, and dehydroepiandrosterone3-sulfate. Although none of the detected steroids induced reproductive behaviors, exposure to steroids from three of the four receptor classes (estrone, 17β-estradiol-3β-glucuronide, or etiocholanolone) increased ventilation rate in males, whereas only etiocholanolone increased ventilation rate in females. Using the ventilation increase as a behavioral bioassay of steroid detection, behavioral cross-adaptation studies in males demonstrated that steroids discriminated at the sensory level are also discriminated behaviorally. These findings suggest the round goby may use steroids as putative pheromones.