Abstract: Insects, like many other animals, use sex pheromones to coordinate their reproductive behaviours. Volatile pheromones are detected by odorant receptors expressed in olfactory receptor neurons (ORNs). Whereas fruit odours typically activate multiple ORN classes, pheromones are thought to act through single dedicated classes of ORN. This model predicts that activation of such an ORN class should be sufficient to trigger the appropriate behavioural response. Here we show that the Drosophila melanogaster male-specific pheromone 11-cis-vaccenyl acetate (cVA) acts through the receptor Or67d to regulate both male and female mating behaviour. Mutant males that lack Or67d inappropriately court other males, whereas mutant females are less receptive to courting males. These data suggest that cVA has opposite effects in the two sexes: inhibiting mating behaviour in males but promoting mating behaviour in females. Replacing Or67d with moth pheromone receptors renders these ORNs sensitive to the corresponding moth pheromones. In such flies, moth pheromones elicit behavioural responses that mimic the normal response to cVA. Thus, activation of a single ORN class is both necessary and sufficient to mediate behavioural responses to the Drosophila sex pheromone cVA.

Abstract: Although many properties of the nervous system are shared among animals and systems, it is not known whether different neuronal circuits use common strategies to guide behaviour. Here we characterize information processing by Caenorhabditis elegans olfactory neurons (AWC) and interneurons (AIB and AIY) that control food- and odour-evoked behaviours. Using calcium imaging and mutations that affect specific neuronal connections, we show that AWC neurons are activated by odour removal and activate the AIB interneurons through AMPA-type glutamate receptors. The level of calcium in AIB interneurons is elevated for several minutes after odour removal, a neuronal correlate to the prolonged behavioural response to odour withdrawal. The AWC neuron inhibits AIY interneurons through glutamate-gated chloride channels; odour presentation relieves this inhibition and results in activation of AIY interneurons. The opposite regulation of AIY and AIB interneurons generates a coordinated behavioural response. Information processing by this circuit resembles information flow from vertebrate photoreceptors to 'OFF' bipolar and 'ON' bipolar neurons, indicating a conserved or convergent strategy for sensory information processing.

Abstract: The mammalian olfactory system mediates various responses, including aversive behaviours to spoiled foods and fear responses to predator odours. In the olfactory bulb, each glomerulus represents a single species of odorant receptor. Because a single odorant can interact with several different receptor species, the odour information received in the olfactory epithelium is converted to a topographical map of multiple glomeruli activated in distinct areas in the olfactory bulb. To study how the odour map is interpreted in the brain, we generated mutant mice in which olfactory sensory neurons in a specific area of the olfactory epithelium are ablated by targeted expression of the diphtheria toxin gene. Here we show that, in dorsal-zone-depleted mice, the dorsal domain of the olfactory bulb was devoid of glomerular structures, although second-order neurons were present in the vacant areas. The mutant mice lacked innate responses to aversive odorants, even though they were capable of detecting them and could be conditioned for aversion with the remaining glomeruli. These results indicate that, in mice, aversive information is received in the olfactory bulb by separate sets of glomeruli, those dedicated for innate and those for learned responses.

Abstract: The CD36 family of transmembrane receptors is present across metazoans and has been implicated biochemically in lipid binding and transport. Several CD36 proteins function in the immune system as scavenger receptors for bacterial pathogens and seem to act as cofactors for Toll-like receptors by facilitating recognition of bacterially derived lipids. Here we show that a Drosophila melanogaster CD36 homologue, Sensory neuron membrane protein (SNMP), is expressed in a population of olfactory sensory neurons (OSNs) implicated in pheromone detection. SNMP is essential for the electrophysiological responses of OSNs expressing the receptor OR67d to (Z)-11-octadecenyl acetate (cis-vaccenyl acetate, cVA), a volatile male-specific fatty-acid-derived pheromone that regulates sexual and social aggregation behaviours. SNMP is also required for the activation of the moth pheromone receptor HR13 by its lipid-derived pheromone ligand (Z)-11-hexadecenal, but is dispensable for the responses of the conventional odorant receptor OR22a to its short hydrocarbon fruit ester ligands. Finally, we show that SNMP is required for responses of OR67d to cVA when ectopically expressed in OSNs not normally activated by pheromones. Because mammalian CD36 binds fatty acids, we suggest that SNMP acts in concert with odorant receptors to capture pheromone molecules on the surface of olfactory dendrites. Our work identifies an unanticipated cofactor for odorant receptors that is likely to have a widespread role in insect pheromone detection. Moreover, these results define a unifying model for CD36 function, coupling recognition of lipid-based extracellular ligands to signalling receptors in both pheromonal communication and pathogen recognition through the innate immune system.

Abstract: In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male–male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain. The dominant theory about how the dramatic differences between male and female behaviour arise in mammals has been that gonadal hormones induce neural circuits early in the development of the brain, inducing or suppressing either male or female characteristics. But new work suggests that the preference to mate as a male or female is not pre-set during development. Pheromone perception has been found to change sexual behaviour in adult female mice. Key to the phenomenon is the vomeronasal organ, an auxiliary olfactory sense organ of unknown function found in the vomer bone, between the nose and mouth. Females with a defective vomeronasal organ display masculine sexual behaviour, suggesting that the effector circuits of both male and female behaviours exist in the brain of each sex, and are switched on or off by gender-specific sensory modulators, at least in females. It is thought that adult humans do not possess functional vomeronasal organs, but this discovery may nonetheless open new avenues for research into sex-specific human behaviour. Female mice with genetic or physical lesions of the vomeronasal organ (VNO) display strikingly masculine sexual behavior, suggesting that the masculine circuitry is actually intact even in females but is normally suppressed by VNO function.

Abstract: Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caeonorhabditis elegans, gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster, we showed that exposure to nutrient-derived odorants can modulate life span and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b resulted in severe olfactory defects, altered adult metabolism, enhanced stress resistance, and extended life span. Our findings indicate that olfaction affects adult physiology and aging in Drosophila, possibly through the perceived availability of nutritional resources, and that olfactory regulation of life span is evolutionarily conserved.

Abstract: Although it is agreed that physicochemical features of molecules determine their perceived odor, the rules governing this relationship remain unknown. A significant obstacle to such understanding is the high dimensionality of features describing both percepts and molecules. We applied a statistical method to reduce dimensionality in both odor percepts and physicochemical descriptors for a large set of molecules. We found that the primary axis of perception was odor pleasantness, and critically, that the primary axis of physicochemical properties reflected the primary axis of olfactory perception. This allowed us to predict the pleasantness of novel molecules by their physicochemical properties alone. Olfactory perception is strongly shaped by experience and learning. However, our findings suggest that olfactory pleasantness is also partially innate, corresponding to a natural axis of maximal discriminability among biologically relevant molecules.

Abstract: Recent studies support the idea of olfactory dysfunction as a very early sign of idiopathic Parkinson's disease (IPD). Aim of the present study was to clinically follow-up patients with idiopathic hyposmia to find out the percentage of patients developing IPD after 4 years time. At baseline, olfactory tests had been combined with transcranial sonography of the substantia nigra and (123)I-FP-CIT SPECT imaging. At the present neurological examination, 7% of the individuals with idiopathic hyposmia had developed clinical IPD. Altogether, 13% presented with abnormalities of the motor system. Our data suggest that a combination of olfactory testing and other tests may constitute a screening tool for the risk to develop IPD.

Abstract: Understanding the relationship between brain and behavior is the fundamental challenge in neuroscience. We focus on chemosensation and chemosensory learning in larval Drosophila and review what is known about its molecular and cellular bases. Detailed analyses suggest that the larval olfactory system, albeit much reduced in cell number, shares the basic architecture, both in terms of receptor gene expression and neuronal circuitry, of its adult counterpart as well as of mammals. With respect to the gustatory system, less is known in particular with respect to processing of gustatory information in the central nervous system, leaving generalizations premature. On the behavioral level, a learning paradigm for the association of odors with food reinforcement has been introduced. Capitalizing on the knowledge of the chemosensory pathways, we review the first steps to reveal the genetic and cellular bases of olfactory learning in larval Drosophila. We argue that the simplicity of the larval chemosensory system, combined with the experimental accessibility of Drosophila on the genetic, electrophysiological, cellular, and behavioral level, makes this system suitable for an integrated understanding of chemosensation and chemosensory learning.

Abstract: The olfactory-driven blood-feeding behaviour of female Aedes aegypti mosquitoes is the primary transmission mechanism by which the arboviruses causing dengue and yellow fevers affect over 40 million individuals worldwide. Bioinformatics analysis has been used to identify 131 putative odourant receptors from the A. aegypti genome that are likely to function in chemosensory perception in this mosquito. Comparison with the Anopheles gambiae olfactory subgenome demonstrates significant divergence of the odourant receptors that reflects a high degree of evolutionary activity potentially resulting from their critical roles during the mosquito life cycle. Expression analyses in the larval and adult olfactory chemosensory organs reveal that the ratio of odourant receptors to antennal glomeruli is not necessarily one to one in mosquitoes.

Abstract: Despite a remarkably precise spatial representation of odorant stimuli in the early stages of olfactory processing, the projections to the olfactory (piriform) cortex are more diffuse and show characteristics of a combinatorial array, with extensive overlap of afferent inputs and widespread intracortical association connections. Furthermore, although there is increasing evidence for the importance of temporal structure in olfactory bulb odorant-evoked output, little is known about how this temporal patterning is translated within cortical neural ensembles. The present study used multichannel electrode arrays and paired single-unit recordings in rat anterior piriform cortex to test several predictions regarding ensemble coding in this system. The results indicate that odorants evoke activity in a spatially scattered ensemble of anterior piriform cortex neurons, and the ensemble activity includes a rich temporal structure. The most pronounced discrimination between different odorants by cortical ensembles occurs during the first inhalation of a 2 s stimulus. The distributed spatial and temporal structure of cortical activity is present at both global and local scales, with neighboring single units contributing to coding of different odorants and active at different phases of the respiratory cycle. Finally, cross-correlogram analyses suggest that cortical unit activity reflects not only afferent input from the olfactory bulb but also intrinsic activity within the intracortical association fiber system. These results provide direct evidence for predictions stemming from anatomical- and theoretical-based models of piriform cortex.

Abstract: This study investigated (1) the influence of verbal and conceptual processing on the retrieval and phenomenological evaluation of olfactory evoked memories, and (2) whether the experienced qualities of retrieved information are affected by olfactory exposure per se. Seventy-two older adults were randomized into one of three cue conditions (odor only, name only, or odor name) and asked to relate any autobiographical event for the given cue. The results indicated that semantic knowledge of an odor’s name significantly affects the age distribution of memories such that the memory peak in childhood observed for odors only was attenuated. Also, experiential factors such as pleasantness and feelings of being brought back in time were lower when odors were presented with their respective names. Olfactory evoked memories were associated with a higher emotional arousal that could not be accounted for by the perceptual stimulation alone. Taken together, the overall pattern of findings suggests that retrieval of olfactory evoked information is sensitive to semantic and conceptual processing, and that odor-evoked representations are more emotional than memories triggered by verbal information.

Abstract: Sheep and goats rapidly establish an exclusive relationship with their neonate following contact with it during a sensitive period of maternal responsiveness induced by the physiological events occurring at parturition. The data concerning the sensory, physiological, and neurobiological factors involved in the activation of both maternal responsiveness and the establishment of selective nursing indicates that these processes are activated simultaneously by the combined action of two main factors, the prepartum rise in circulating estrogen and the vaginocervical stimulation (VCS) caused by fetus expulsion. On the one hand, these two factors act on a neural network including the main olfactory system (MOB), the medial preoptic area (MPOA), and the paraventricular nucleus of the hypothalamus (PVN) to induce maternal responsiveness towards any neonate. The intracerebral release of oxytocin (OT) from the PVN, and the triggering of olfactory attraction for amniotic fluid (AF) are key elements in this process. On the other hand, VCS at birth also sets the MOB ready to memorize the individual odor of the neonate, through the release of peptides and neurotransmitters (noradrenaline and acetylcholine). In addition to the MOB, the network involved in recognition mainly includes the medial and cortical amygdala. Across consolidation processes, reorganization occurs in the network engaged in lamb recognition. Whether this memorization may be potentiated by other sensory cues is not known. The identification of the chemosensory compounds involved in the attraction for AF and in the recognition of the neonate is important for understanding the mechanisms of maternal attachment. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 49: 54–70, 2007

Abstract: Two receptors for vasopressin (Avp) are expressed in the brain, the Avp 1a receptor (Avpr1a) and the Avp 1b receptor (Avpr1b). To investigate the role of Avpr1a in behaviors in mice more extensively, we generated a line of mice lacking a functional Avpr1a (knockout, Avpr1a−/−). We first performed a baseline phenotypic screen of the Avpr1a knockouts followed by a more detailed analysis of their circadian rhythms and olfactory function. When free-running in constant darkness, the Avpr1a−/− mice have a longer circadian tau than the wild types. There are also subtle olfactory deficits in Avpr1a−/− mice as measured in an olfactory habituation/dishabituation test and in the discrimination of female urine from male urine using an operant testing paradigm. An extensive body of research has shown that manipulation of the Avpr1a alters behavior, including aggression and social recognition. Therefore, we expected profound behavioral deficits in mice lacking the Avpr1a gene. Contrary to our expectations, social aggression, anxiety-like behavior and social recognition are unaffected in this line of Avpr1a knockout mice. These data suggest either that the Avpr1a is not as critical as we thought for social behavior in mice or, more likely, that the neural circuitry underlying aggression and other social behaviors compensates for the life-long loss of the Avpr1a. However, the olfactory deficits observed in the Avpr1a−/− mice suggest that Avp and Avpr1a drugs may affect behavior, in part, by modulation of chemosensory systems.

Abstract: Most animal species rely on odorant compounds to locate food, predators, or toxins. The sense of smell is also involved in animal communication, and revealing the underlying mechanisms will therefore facilitate a deeper understanding of animal behaviour. Since the 1940s different theories have speculated on the fundamental basis of olfaction. It was assumed that odorant molecules were recognized by selective protein receptors in the nose, triggering a nervous signal processed by the brain. The discovery of these receptors in the early 1990s allowed great progress in understanding the physiological and biochemical principles of olfaction. An overview of the different mechanisms involved in the coding of odour character as well as odour intensity is presented here, focusing on the biochemical basis of odorant recognition. Despite the enormous progress achieved in recent years, details of odorant-receptor interaction at the molecular level and the mechanisms of olfactory receptor activation are poorly understood. The likely role of metal ions in odorant recognition is discussed, and also the perireceptor events involved in odorant transport and biotransformation, with a view to providing a comprehensive overview of mammalian olfaction to guide future computational structural models and the design of functional experiments. Recent studies have analysed the olfactory genome of several species, providing information about the evolution of olfaction. The role of the olfactory system in animal communication is also described.

Abstract: The sense of smell plays an important role in guiding the behaviour of many animals including insects. The attractiveness of a volatile is not only dependent on the nature of the chemical, but might change with the physiological status (e.g., age/hormone or mating status) or environmental conditions (e.g., photoperiod or temperature) of the individual. Here we summarize our studies focused on the plasticity of olfactory-guided behaviour and its neurobiological basis linked with the physiological status in Lepidoptera and migratory locusts. In moths and locusts, age and juvenile hormone changed the behavioural responses to pheromones. In moths, mating had an effect on pheromone responses in males and plant odour responses in females. In all cases of behavioural plasticity studied, we found changes in the sensitivity of olfactory interneurons in the antennal lobe, whereas the peripheral system does not seem to show any plasticity in that context. Changes in the central nervous system were slow under the influence of juvenile hormone (days) or fast after mating (minutes). The olfactory system seems thus to adapt to the physiological or environmental situation of an animal to avoid a waste of energy. We discuss possible mechanisms underlying the observed plasticity.

Abstract: Physical traces underlying simple memories can be confined to a single group of cells in the brain. In the fly Drosophila melanogaster, the Kenyon cells of the mushroom bodies house traces for both appetitive and aversive odor memories. The adenylate cyclase protein, Rutabaga, has been shown to mediate both traces. Here, we show that, for appetitive learning, another group of cells can additionally accommodate a Rutabaga-dependent memory trace. Localized expression of rutabaga in either projection neurons, the first-order olfactory interneurons, or in Kenyon cells, the second-order interneurons, is sufficient for rescuing the mutant defect in appetitive short-term memory. Thus, appetitive learning may induce multiple memory traces in the first- and second-order olfactory interneurons using the same plasticity mechanism. In contrast, aversive odor memory of rutabaga is rescued selectively in the Kenyon cells, but not in the projection neurons. This difference in the organization of memory traces is consistent with the internal representation of reward and punishment.

Abstract: A single type of olfactory sensilla on maxillary palps in many species of mosquitoes houses a very sensitive olfactory receptor neuron (ORN) for carbon dioxide reception. We performed extensive single sensillum recordings from this peg sensillum in Culex quinquefasciatus and have characterized the response threshold and kinetics for CO2 reception, with a detection threshold less than the CO2 concentration in the atmosphere. This ORN responded in a tonic mode to lower concentrations of CO2, whereas higher concentrations generated a phasic-tonic mode of action potential firing. Sensillum potentials accurately represented the response magnitude and kinetics of carbon dioxide–elicited excitatory responses. Stimulation of these ORNs with human breath, a complex mixture of mosquito kairomones and up to 4.5% CO2, elicited excitatory responses that were reliably detected by CO2-sensitive ORNs. Another ORN housed in these sensilla responded to 1-octen-3-ol and to various plant-derived compounds, particularly floral and green leaf volatiles. This ORN showed remarkable sensitivity to the natural enantiomer, (R)-()-1-octen3-ol, rivaling pheromone-detecting ORNs in moths. Maximum neuronal response was elicited with a 10 ng dose. A biological, ecological role of maxillary palps in detection of plant- and nectar-related sources is proposed.

Abstract: Object recognition is a crucial component of both visual and auditory perception. It is also critical for olfaction. Most odours are composed of 10s or 100s of volatile components, yet they are perceived as unitary perceptual events against a continually shifting olfactory background (i.e. figure-ground segregation). We argue here that this occurs by rapid central adaptation to background odours combined with a pattern-matching system to recognise discrete sets of spatial and temporal olfactory features-an odour object. We present supporting neuropsychological, learning, and developmental evidence and then describe the neural circuitry which underpins this. The vagaries of an object-recognition approach are then discussed, with emphasis on the putative importance of memory, multimodal representations, and top-down processing.

Abstract: The vertebrate olfactory bulb is a remarkably organized neuronal structure, in which hundreds of functionally different sensory inputs are organized into a highly stereotyped topographical map. How this wiring is achieved is not yet understood. Here, we show that the olfactory bulb topographical map is modified in adenylyl cyclase 3 (adenylate cyclase 3)-deficient mice. In these mutants, axonal projection targets corresponding to specific odorant receptors are disorganized, are no longer exclusively innervated by functionally identical axonal projections and shift dramatically along the anteroposterior axis of the olfactory bulb. Moreover, the cyclase depletion leads to the prevention of neuropilin 1 (Nrp1) expression in olfactory sensory neuron axonal projections. Taken together, our data point to a major role played by a crucial element of the odorant-induced transduction cascade, adenylyl cyclase 3, in the targeting of olfactory sensory neuron axons towards the brain. This mechanism probably involves the regulation of receptor genes known to be crucial in axonal guidance processes.

Abstract: Background. A systematic investigation of long-term follow-up results after microsurgical treatment of patients harbouring an olfactory groove meningioma, particularly with regard to postoperative olfactory and mental function, has rarely been performed. We reassessed a series of patients treated microsurgically for an olfactory groove meningioma in regard to clinical presentation, surgical approaches and long-term functional outcome.

Abstract: The research on olfactory sense in virtual reality has gradually expanded even though the technology is still premature. We have developed an olfactory display composed of multiple solenoid valves. In the present study, an extended olfactory display, where 32 component odors can be blended in any recipe, is described; the previous version has only 8 odor components. The size was unchanged even though the number of odor components was four times larger than that in the previous display. The complexity of blending was greatly reduced because of algorithm improvement. The blending method and the fundamental experiment using a QCM (quartz crystal microbalance) sensor are described here

Abstract: The olfactory response of maggots (the larvae of cyclorrhaphous flies) and its neuroanatomical basis have been a subject for scientific investigation since the 17th century, preoccupying both fundamental and applied scientists. Despite its apparently arcane nature, the subject raises a series of major neurobiological problems, in particular, the relationship between the number of odours that can be detected and the apparently simple systems of detection and processing available to larvae. Molecular biological techniques in both neuroanatomy and cell biology have made it possible to begin to resolve some of these problems, if data from a wide range of studies are integrated. Four sectors of research on a large number of species are reviewed: the behaviour involved in the olfactory response, the wide range of odours that can be detected, the neuroanatomical basis of olfaction in cyclorrhaphous larvae and the number of receptors involved in detecting these odours. Finally, a neuroanatomical model of olfactory processing is presented, together with perspectives for future research, emphasising the importance of studying the ecology of the species under investigation.

Abstract: Although numerous functional magnetic resonance imaging (FMRI) studies have been performed on the processing of olfactory information, the intranasal trigeminal system so far has not received much attention. In the present study, we sought to delineate the neural correlates of trigeminal stimulation using carbon dioxide (CO2) presented to the left or right nostril. Fifteen righthanded men underwent FMRI using single runs of 3 conditions (CO2 in the right and the left nostrils and an olfactory stimulant—phenyl ethyl alcohol—in the right nostril). As expected, olfactory activations were located in the orbitofrontal cortex (OFC), amygdala, and rostral insula. For trigeminal stimulation, activations were found in ‘‘trigeminal’’ and ‘‘olfactory’’ regions including the pre- and postcentral gyrus, the cerebellum, the ventrolateral thalamus, the insula, the contralateral piriform cortex, and the OFC. Left compared with right side stimulations resulted in stronger cerebellar and brain stem activations; right versus left stimulation resulted in stronger activations of the superior temporal sulcus and OFC. These results suggest a trigeminal processing system that taps into similar cortical regions and yet is separate from that of the olfactory system. The overlapping pattern of cortical activation for trigeminal and olfactory stimuli is assumed to be due to the intimate connections in the processing of information from the 2 major intranasal chemosensory systems.