Olfaction, the sense of smell detects and discriminate odors as well as social cues which influence our innate responses. The olfactory system in human beings is found to be weak as compared to other ...animals; however, it seems to be very precise. It can detect and discriminate millions of chemical moieties (odorants) even in minuscule quantities. The process initiates with the binding of odorants to specialized olfactory receptors, encoded by a large family of Olfactory Receptor (OR) genes belonging to the G-protein-coupled receptor superfamily. Stimulation of ORs converts the chemical information encoded in the odorants, into respective neuronal action-potentials which causes depolarization of olfactory sensory neurons. The olfactory bulb relays this signal to different parts of the brain for processing. Odors are encrypted using a combinatorial approach to detect a variety of chemicals and encode their unique identity. The discovery of functional OR genes and proteins provided an important information to decipher the genomic, structural and functional basis of olfaction. ORs constitute 17 gene families, out of which 4 families were reported to contain more than hundred members each. The olfactory machinery is not limited to GPCRs; a number of non- GPCRs is also employed to detect chemosensory stimuli. The article provides detailed information about such olfaction machinery, structures, transduction mechanism, theories of odor perception, and challenges in the olfaction research. It covers the structural, functional and computational studies carried out in the olfaction research in the recent past.
Mammals rely heavily on olfaction to interact adequately with each other and with their environment. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and ...pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant, trace amine-associated receptor and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.
Male moths efficiently recognize conspecific sex pheromones thanks to their highly accurate and specific olfactory system. The Heliothis/Helicoverpa species are regarded as good models for studying ...the perception of sex pheromones. In this study, we performed a series of experiments to investigate the peripheral mechanisms of pheromone coding in two-closely related species, Helicoverpa armigera and H. assulta. The morphology and distribution patterns of sensilla trichoidea are similar between the two species when observed at the scanning electron microscope, but their performances are different. In H. armigera, three functional types of sensilla trichoidea (A, B and C) were found to respond to different pheromone components, while in H. assulta only two types of such sensilla (A and C) could be detected. The response profiles of all types of sensilla trichoidea in the two species well matched the specificities of the pheromone receptors (PRs) expressed in the same sensilla, as measured in voltage-clamp experiments. The expressions of PRs in neighboring olfactory sensory neurons (OSNs) within the same trichoid sensillum were further confirmed by in situ hybridization. Our results show how the same pheromone components can code for different messages at the periphery of two Helicoverpa species.
The mouse olfactory sensory neuron (OSN) repertoire is composed of 10 million cells and each expresses one olfactory receptor (OR) gene from a pool of over 1000. Thus, the nose is sub-stratified into ...more than a thousand OSN subtypes. Here, we employ and validate an RNA-sequencing-based method to quantify the abundance of all OSN subtypes in parallel, and investigate the genetic and environmental factors that contribute to neuronal diversity. We find that the OSN subtype distribution is stereotyped in genetically identical mice, but varies extensively between different strains. Further, we identify
-acting genetic variation as the greatest component influencing OSN composition and demonstrate independence from OR function. However, we show that olfactory stimulation with particular odorants results in modulation of dozens of OSN subtypes in a subtle but reproducible, specific and time-dependent manner. Together, these mechanisms generate a highly individualized olfactory sensory system by promoting neuronal diversity.
Modulation of sensory perception by homeostatic feedback from physiological states is central to innate purposive behaviors. Olfaction is an important predictive modality for feeding‐related ...behaviors and its modulation has been associated with hunger‐satiety states. However, the mechanisms mapping internal states to chemosensory processing in order to modify behavior are poorly understood. In the zebrafish olfactory epithelium, a subset of olfactory sensory neurons (OSNs) and the terminal nerve projections express neuropeptide Y (NPY). Using a combination of neuronal activity and behavioral evaluation, we find that NPY signaling in the peripheral olfactory system of zebrafish is correlated with its nutritional state and is both necessary and sufficient for the olfactory perception of food‐related odorants. NPY activity dynamically modulates the microvillar OSN activation thresholds and acts cooperatively with amino acid signaling resulting in a switch‐like increase in OSN sensitivity in starved animals. We suggest that cooperative activation of phospholipase C by convergent signaling from NPY and amino acid receptors is central to this heightened sensitivity. This study provides ethologically relevant, physiological evidence for NPY signaling in the modulation of OSN sensitivity to food‐associated amino acid cues. We demonstrate sensory gating directly at the level of OSNs and identify a novel mechanistic framework for tuning olfactory sensitivity to prevailing energy states.
Cover Image for this issue: https://doi.org/10.1111/jnc.15091
Neuropeptide Y, an orexigenic neuropeptide, is expressed in the OSNs and the TN neurons of the OB of zebrafish. Under conditions of starvation, the levels of this peptide increase in the OE, OB and TN. We show that this increase in NPY signalling leads to an increase in the sensitivity of OSNs to food‐associated odorants. Relative to fed animals, exposure of starved animals to food‐related odorants leads to greater OSN activation, which is manifested as an increased attraction to the food cues. (OE: olfactory epithelium; OB: Olfactory bulb; TN; Terminal Nerve; OSN: Olfactory sensory neurons).
Cover Image for this issue: https://doi.org/10.1111/jnc.15091
Olfactory sensory neurons (OSNs) of the vertebrate olfactory epithelium (OE) undergo continuous turnover but also regenerate efficiently when the OE is acutely damaged by traumatic injury. Two ...distinct pools of neuronal stem/progenitor cells, the globose (GBCs), and horizontal basal cells (HBCs) have been shown to selectively contribute to intrinsic OSN turnover and damage‐induced OE regeneration, respectively. For both types of progenitors, their rate of cell divisions and OSN production must match the actual loss of cells to maintain or to re‐establish sensory function. However, signals that communicate between neurons or glia cells of the OE and resident neurogenic progenitors remain largely elusive. Here, we investigate the effect of purinergic signaling on cell proliferation and OSN neurogenesis in the zebrafish OE. Purine stimulation elicits transient Ca2+ signals in OSNs and distinct non‐neuronal cell populations, which are located exclusively in the basal OE and stain positive for the neuronal stem cell marker Sox2. The more apical population of Sox2‐positive cells comprises evenly distributed glia‐like sustentacular cells (SCs) and spatially restricted GBC‐like cells, whereas the more basal population expresses the HBC markers keratin 5 and tumor protein 63 and lines the entire sensory OE. Importantly, exogenous purine stimulation promotes P2 receptor‐dependent mitotic activity and OSN generation from sites where GBCs are located but not from HBCs. We hypothesize that purine compounds released from dying OSNs modulate GBC progenitor cell cycling in a dose‐dependent manner that is proportional to the number of dying OSNs and, thereby, ensures a constant pool of sensory neurons over time.
Olfactory sensory neurons (OSNs) undergo lifelong renewal from two distinct tissue‐resident progenitor pools. Globose basal cells (GBCs) predominantly contribute to olfactory neurogenesis in intact tissue, while horizontal basal cells (HBCs) become selectively activated upon injury. Here, Stefan Fuss and co‐authors investigate the effect of purinergic signalling on cell proliferation and olfactory neurogenesis using zebrafish. They show that purine compounds stimulate olfactory neurogenesis selectively from GBC but not HBC progenitors, suggesting a mechanistic link between the number of dying OSNs, ATP release, and the rate of GBC progenitor cell divisions.
Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate ...targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2
) mitral cells (MCs, second-order neurons) play crucial roles in transmitting attractive social signals from the PV MOB to the anterior part of medial amygdala (MeA). Semaphorin 3F, a repulsive ligand to Nrp2, regulates both migration of Nrp2
MCs to the PV MOB and their axonal projection to the anterior MeA. In the MC-specific Nrp2 knockout mice, circuit formation of Nrp2
MCs and odour-induced attractive social responses are impaired. In utero, electroporation demonstrates that activation of the Nrp2 gene in MCs is sufficient to instruct their circuit formation from the PV MOB to the anterior MeA.
The Oriental fruit fly, Bactrocera dorsalis, is a highly destructive pest of various fruits. The reproductive and host-finding behaviors of this species are affected by several plant semiochemicals ...that are perceived through chemosensory receptors. However, the chemosensory mechanisms by which this perception occurs have not been fully elucidated. We conducted RNA sequencing analysis of the chemosensory organs of B. dorsalis to identify the genes coding for chemosensory receptors. We identified 60 olfactory receptors (ORs), 17 gustatory receptors and 23 ionotropic receptors—including their homologs and variants—from the transcriptome of male antennae and proboscises. We functionally analyzed ten ORs co-expressed with the obligatory co-receptor ORCO in Xenopus oocytes to identify their ligands. We tested 24 compounds including attractants for several Bactrocera species and volatiles from the host fruits of B. dorsalis. We found that BdorOR13a co-expressed with ORCO responded robustly to 1-octen-3-ol. BdorOR82a co-expressed with ORCO responded significantly to geranyl acetate, but responded weakly to farnesenes (a mixture of isomers) and linalyl acetate. These four compounds were subsequently subjected to behavioral bioassays. When each of the aforementioned compound was presented in combination with a sphere model as a visual cue to adult flies, 1-octen-3-ol, geranyl acetate, and farnesenes significantly enhanced landing behavior in mated females, but not in unmated females or males. These results suggest that the ORs characterized in the present study are involved in the perception of plant volatiles that affect host-finding behavior in B. dorsalis.
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•Chemosensory receptors were identified in Bactrocera dorsalis by RNA sequencing analysis.•Two olfactory receptors were characterized by functional analysis using Xenopus oocytes as a heterologous expression system.•Volatiles identified as ligands for olfactory receptors significantly enhanced the landing behavior of mated females.
Olfactory receptors (ORs) are expressed in the olfactory epithelium, where they detect odorants, but also in other tissues with additional functions. Some ORs are even overexpressed in tumor cells. ...In this study, we identified ORs expressed in enterochromaffin tumor cells by RT-PCR, showing that single cells can co-express several ORs. Some of the receptors identified were already reported in other tumors, but they are orphan (without known ligand), as it is the case for most of the hundreds of human ORs. Thus, genes coding for human ORs with known ligands were transfected into these cells, expressing functional heterologous ORs. The in vitro stimulation of these cells by the corresponding OR odorant agonists promoted cell invasion of collagen gels. Using LNCaP prostate cancer cells, the stimulation of the PSGR (Prostate Specific G protein-coupled Receptor), an endogenously overexpressed OR, by β-ionone, its odorant agonist, resulted in the same phenotypic change. We also showed the involvement of a PI3 kinase γ dependent signaling pathway in this promotion of tumor cell invasiveness triggered by OR stimulation. Finally, after subcutaneous inoculation of LNCaP cells into NSG immunodeficient mice, the in vivo stimulation of these cells by the PSGR agonist β-ionone significantly enhanced metastasis emergence and spreading.
Odours are transported in turbulent plumes, which result in rapid concentration fluctuations
that contain rich information about the olfactory scenery, such as the composition and location of an ...odour source
. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond odour pulse patterns produce distinct responses in olfactory receptor neurons. In operant conditioning experiments, mice discriminated temporal correlations of rapidly fluctuating odours at frequencies of up to 40 Hz. In imaging and electrophysiological recordings, such correlation information could be readily extracted from the activity of mitral and tufted cells-the output neurons of the olfactory bulb. Furthermore, temporal correlation of odour concentrations
reliably predicted whether odorants emerged from the same or different sources in naturalistic environments with complex airflow. Experiments in which mice were trained on such tasks and probed using synthetic correlated stimuli at different frequencies suggest that mice can use the temporal structure of odours to extract information about space. Thus, the mammalian olfactory system has access to unexpectedly fast temporal features in odour stimuli. This endows animals with the capacity to overcome key behavioural challenges such as odour source separation
, figure-ground segregation
and odour localization
by extracting information about space from temporal odour dynamics.
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