Sample records for non-conventional olfactory receptor

  1. Discrimination between olfactory receptor agonists and non-agonists.

    PubMed

    Topin, Jérémie; de March, Claire A; Charlier, Landry; Ronin, Catherine; Antonczak, Serge; Golebiowski, Jérôme

    2014-08-11

    A joint approach combining free-energy calculations and calcium-imaging assays on the broadly tuned human 1G1 olfactory receptor is reported. The free energy of binding of ten odorants was computed by means of molecular-dynamics simulations. This state function allows separating the experimentally determined eight agonists from the two non-agonists. This study constitutes a proof-of-principle for the computational deorphanization of olfactory receptors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Olfactory Ionotropic Receptors in Mosquito Aedes albopictus (Diptera: Culicidae).

    PubMed

    Chen, Qian; Man, Yahui; Li, Jianyong; Pei, Di; Wu, Wenjian

    2017-09-01

    Ionotropic glutamate receptors (iGluRs) are a conserved family of ligand-gated ion channels that primarily function to mediate neuronal communication at synapses. A variant subfamily of iGluRs, the ionotropic receptors (IRs), was recently identified in insects and proved with the function in odorant recognition. Ionotropic receptors participate in a distinct olfactory signaling pathway that is independent of olfactory receptors activity. In the present study, we identify 102 putative IR genes, dubbed as AalbIr genes, in mosquito Aedes albopictus (Skuse) by in silico comparative sequence analysis. Among AalbIr genes, 19 show expression in the female antenna by RT-PCR. These putative olfactory AalbIRs share four conservative hydrophobic domains of amino acids, similar to the transmembrane and ion channel pore regions found in conventional iGluRs. To determine the potential function of these olfactory AalbIRs in host-seeking, we compared their transcript expression levels in the antennae of blood-fed females with that of non-blood-fed females by quantitative real-time RT-PCR. Three AalbIr genes showed downregulation when the mosquito finished a bloodmeal. These results may help to improve our understanding of the IR-mediated olfactory signaling in mosquitoes. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Evolution of olfactory receptors.

    PubMed

    Hoover, Kara C

    2013-01-01

    Olfactory receptors are a specialized set of receptor cells responsible for the detection of odors. These cells are G protein-coupled receptors and expressed in the cell membranes of olfactory sensory neurons. Once a cell is activated by a ligand, it initiates a signal transduction cascade that produces a nerve impulse to the brain where odor perception is processed. Vertebrate olfactory evolution is characterized by birth-and-death events, a special case of the stochastic continuous time Markov process. Vertebrate fish have three general types of receptor cells (two dedicated to pheromones). Terrestrial animals have different epithelial biology due to the specialized adaptation to detecting airborne odors. Two general classes of olfactory receptor gene reflect the vertebrate marine heritage (Class I) and the derived amphibian, reptile, and mammal terrestrial heritage (Class II). While we know much about olfactory receptor cells, there are still areas where our knowledge is insufficient, such as intra-individual diversity throughout the life time, epigenetic processes acting on olfactory receptors, and association of ligands to specific cells.

  4. Ionotropic crustacean olfactory receptors.

    PubMed

    Corey, Elizabeth A; Bobkov, Yuriy; Ukhanov, Kirill; Ache, Barry W

    2013-01-01

    The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs), the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs), as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  5. Olfactory receptor neuron profiling using sandalwood odorants.

    PubMed

    Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

    2004-07-01

    The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

  6. Human olfactory receptor responses to odorants

    PubMed Central

    Mainland, Joel D; Li, Yun R; Zhou, Ting; Liu, Wen Ling L; Matsunami, Hiroaki

    2015-01-01

    Although the human olfactory system is capable of discriminating a vast number of odors, we do not currently understand what chemical features are encoded by olfactory receptors. In large part this is due to a paucity of data in a search space covering the interactions of hundreds of receptors with billions of odorous molecules. Of the approximately 400 intact human odorant receptors, only 10% have a published ligand. Here we used a heterologous luciferase assay to screen 73 odorants against a clone library of 511 human olfactory receptors. This dataset will allow other researchers to interrogate the combinatorial nature of olfactory coding. PMID:25977809

  7. Olfactory receptor antagonism between odorants

    PubMed Central

    Oka, Yuki; Omura, Masayo; Kataoka, Hiroshi; Touhara, Kazushige

    2004-01-01

    The detection of thousands of volatile odorants is mediated by several hundreds of different G protein-coupled olfactory receptors (ORs). The main strategy in encoding odorant identities is a combinatorial receptor code scheme in that different odorants are recognized by different sets of ORs. Despite increasing information on agonist–OR combinations, little is known about the antagonism of ORs in the mammalian olfactory system. Here we show that odorants inhibit odorant responses of OR(s), evidence of antagonism between odorants at the receptor level. The antagonism was demonstrated in a heterologous OR-expression system and in single olfactory neurons that expressed a given OR, and was also visualized at the level of the olfactory epithelium. Dual functions of odorants as an agonist and an antagonist to ORs indicate a new aspect in the receptor code determination for odorant mixtures that often give rise to novel perceptual qualities that are not present in each component. The current study also provides insight into strategies to modulate perceived odorant quality. PMID:14685265

  8. Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

    PubMed

    Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

    1984-08-01

    A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity.

  9. Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

    PubMed Central

    Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

    1984-01-01

    A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity. Images PMID:6206495

  10. Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.

    PubMed

    Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G; Grison, Alice; Gustincich, Stefano

    2016-01-01

    Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

  11. Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

    PubMed Central

    Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G.; Grison, Alice; Gustincich, Stefano

    2016-01-01

    Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain. PMID:27458372

  12. Non-redundant coding of aversive odours in the main olfactory pathway.

    PubMed

    Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

    2013-05-23

    Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

  13. Non-redundant coding of aversive odours in the main olfactory pathway

    PubMed Central

    Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

    2013-01-01

    Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

  14. Nested Expression Domains for Odorant Receptors in Zebrafish Olfactory Epithelium

    NASA Astrophysics Data System (ADS)

    Weth, Franco; Nadler, Walter; Korsching, Sigrun

    1996-11-01

    The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

  15. Expression of ionotropic receptors in terrestrial hermit crab's olfactory sensory neurons

    PubMed Central

    Groh-Lunow, Katrin C.; Getahun, Merid N.; Grosse-Wilde, Ewald; Hansson, Bill S.

    2015-01-01

    Coenobitidae are one out of at least five crustacean lineages which independently succeeded in the transition from water to land. This change in lifestyle required adaptation of the peripheral olfactory organs, the antennules, in order to sense chemical cues in the new terrestrial habitat. Hermit crab olfactory aesthetascs are arranged in a field on the distal segment of the antennular flagellum. Aesthetascs house approximately 300 dendrites with their cell bodies arranged in spindle-like complexes of ca. 150 cell bodies each. While the aesthetascs of aquatic crustaceans have been shown to be the place of odor uptake and previous studies identified ionotropic receptors (IRs) as the putative chemosensory receptors expressed in decapod antennules, the expression of IRs besides the IR co-receptors IR25a and IR93a in olfactory sensory neurons (OSNs) has not been documented yet. Our goal was to reveal the expression and distribution pattern of non-co-receptor IRs in OSNs of Coenobita clypeatus, a terrestrial hermit crab, with RNA in situ hybridization. We expanded our previously published RNAseq dataset, and revealed 22 novel IR candidates in the Coenobita antennules. We then used RNA probes directed against three different IRs to visualize their expression within the OSN cell body complexes. Furthermore we aimed to characterize ligand spectra of single aesthetascs by recording local field potentials and responses from individual dendrites. This also allowed comparison to functional data from insect OSNs expressing antennal IRs. We show that this orphan receptor subgroup with presumably non-olfactory function in insects is likely the basis of olfaction in terrestrial hermit crabs. PMID:25698921

  16. Role of a Ubiquitously Expressed Receptor in the Vertebrate Olfactory System

    PubMed Central

    DeMaria, Shannon; Berke, Allison P.; Van Name, Eric; Heravian, Anisa; Ferreira, Todd

    2013-01-01

    Odorant cues are recognized by receptors expressed on olfactory sensory neurons, the primary sensory neurons of the olfactory epithelium. Odorant receptors typically obey the “one receptor, one neuron” rule, in which the receptive field of the olfactory neuron is determined by the singular odorant receptor that it expresses. Odor-evoked receptor activity across the population of olfactory neurons is then interpreted by the brain to identify the molecular nature of the odorant stimulus. In the present study, we characterized the properties of a C family G-protein-coupled receptor that, unlike most other odorant receptors, is expressed in a large population of microvillous sensory neurons in the zebrafish olfactory epithelium and the mouse vomeronasal organ. We found that this receptor, OlfCc1 in zebrafish and its murine ortholog Vmn2r1, is a calcium-dependent, low-sensitivity receptor specific for the hydrophobic amino acids isoleucine, leucine, and valine. Loss-of-function experiments in zebrafish embryos demonstrate that OlfCc1 is required for olfactory responses to a diverse mixture of polar, nonpolar, acidic, and basic amino acids. OlfCc1 was also found to promote localization of other OlfC receptor family members to the plasma membrane in heterologous cells. Together, these results suggest that the broadly expressed OlfCc1 is required for amino acid detection by the olfactory system and suggest that it plays a role in the function and/or intracellular trafficking of other olfactory and vomeronasal receptors with which it is coexpressed. PMID:24048853

  17. Spatial pattern of receptor expression in the olfactory epithelium.

    PubMed Central

    Nef, P; Hermans-Borgmeyer, I; Artières-Pin, H; Beasley, L; Dionne, V E; Heinemann, S F

    1992-01-01

    A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system. Images PMID:1384038

  18. Functional identification and reconstitution of an odorant receptor in single olfactory neurons

    PubMed Central

    Touhara, Kazushige; Sengoku, Shintaro; Inaki, Koichiro; Tsuboi, Akio; Hirono, Junzo; Sato, Takaaki; Sakano, Hitoshi; Haga, Tatsuya

    1999-01-01

    The olfactory system is remarkable in its capacity to discriminate a wide range of odorants through a series of transduction events initiated in olfactory receptor neurons. Each olfactory neuron is expected to express only a single odorant receptor gene that belongs to the G protein coupled receptor family. The ligand–receptor interaction, however, has not been clearly characterized. This study demonstrates the functional identification of olfactory receptor(s) for specific odorant(s) from single olfactory neurons by a combination of Ca2+-imaging and reverse transcription–coupled PCR analysis. First, a candidate odorant receptor was cloned from a single tissue-printed olfactory neuron that displayed odorant-induced Ca2+ increase. Next, recombinant adenovirus-mediated expression of the isolated receptor gene was established in the olfactory epithelium by using green fluorescent protein as a marker. The infected neurons elicited external Ca2+ entry when exposed to the odorant that originally was used to identify the receptor gene. Experiments performed to determine ligand specificity revealed that the odorant receptor recognized specific structural motifs within odorant molecules. The odorant receptor-mediated signal transduction appears to be reconstituted by this two-step approach: the receptor screening for given odorant(s) from single neurons and the functional expression of the receptor via recombinant adenovirus. The present approach should enable us to examine not only ligand specificity of an odorant receptor but also receptor specificity and diversity for a particular odorant of interest. PMID:10097159

  19. Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

    PubMed Central

    Saven, Jeffery G.; Matsunami, Hiroaki; Eckenhoff, Roderic G.

    2015-01-01

    Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug. PMID:25829447

  20. Integrated Approaches for Genome-wide Interrogation of the Druggable Non-olfactory G Protein-coupled Receptor Superfamily.

    PubMed

    Roth, Bryan L; Kroeze, Wesley K

    2015-08-07

    G-protein-coupled receptors (GPCRs) are frequent and fruitful targets for drug discovery and development, as well as being off-targets for the side effects of a variety of medications. Much of the druggable non-olfactory human GPCR-ome remains under-interrogated, and we present here various approaches that we and others have used to shine light into these previously dark corners of the human genome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  2. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    PubMed

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  3. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination.

    PubMed

    Enwere, Emeka; Shingo, Tetsuro; Gregg, Christopher; Fujikawa, Hirokazu; Ohta, Shigeki; Weiss, Samuel

    2004-09-22

    Previous studies demonstrating olfactory interneuron involvement in olfactory discrimination and decreased proliferation in the forebrain subventricular zone with age led us to ask whether olfactory neurogenesis and, consequently, olfactory discrimination were impaired in aged mice. Pulse labeling showed that aged mice (24 months of age) had fewer new interneurons in the olfactory bulb than did young adult (2 months of age) mice. However, the aged mice had more olfactory interneurons in total than their younger counterparts. Aged mice exhibited no differences from young adult mice in their ability to discriminate between two discrete odors but were significantly poorer at performing discriminations between similar odors (fine olfactory discrimination). Leukemia inhibitory factor receptor heterozygote mice, which have less neurogenesis and fewer olfactory interneurons than their wild-type counterparts, performed more poorly at fine olfactory discrimination than the wild types, suggesting that olfactory neurogenesis, rather than the total number of interneurons, was responsible for fine olfactory discrimination. Immunohistochemistry and Western blot analyses revealed a selective reduction in expression levels of epidermal growth factor (EGF) receptor (EGFR) signaling elements in the aged forebrain subventricular zone. Waved-1 mutant mice, which express reduced quantities of transforming growth factor-alpha, the predominant EGFR ligand in adulthood, phenocopy aged mice in olfactory neurogenesis and performance on fine olfactory discrimination tasks. These results suggest that the impairment in fine olfactory discrimination with age may result from a reduction in EGF-dependent olfactory neurogenesis.

  4. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila.

    PubMed

    Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I; Angel, Cristian; Campusano, Jorge M

    2015-01-01

    The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila.

  5. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

    PubMed Central

    Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano, Jorge M.

    2015-01-01

    The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID:26380118

  6. The essence of appetite: Does olfactory receptor variation play a role?

    USDA-ARS?s Scientific Manuscript database

    Olfactory receptors are G-protein coupled chemoreceptors expressed on millions of olfactory sensory neurons within the nasal cavity. These receptors detect environmental odorants and signal the brain regarding the location of feed, potential mates, and the presence of possible threats (e.g., predato...

  7. Expression of olfactory receptors in different life stages and life histories of wild Atlantic salmon (Salmo salar).

    PubMed

    Johnstone, K A; Lubieniecki, K P; Koop, B F; Davidson, W S

    2011-10-01

    It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. However, the key components of the molecular pathway involved in imprinting and homing are still unknown. If odorants are involved in salmon homing migration, then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, we examined the expression profiles of a suite of genes encoding olfactory receptors and other olfactory-related genes in the olfactory rosettes of different life stages in two anadromous and one non-anadromous wild Atlantic salmon populations from Newfoundland, Canada. We identified seven differentially expressed OlfC genes in juvenile anadromous salmon compared to returning adults in both populations of anadromous Atlantic salmon. The salmon from the Campbellton River had an additional 10 genes that were differentially expressed in juveniles compared to returning adults. There was no statistically significant difference in gene expression of any of the genes in the non-anadromous population (P < 0.01). The function of the OlfC gene products is not clear, but they are predicted to be amino acid receptors. Other studies have suggested that salmon use amino acids for imprinting and homing. This study, the first to examine the expression of olfactory-related genes in wild North American Atlantic salmon, has identified seven OlfC genes that may be involved in the imprinting and homeward migration of anadromous Atlantic salmon. © 2011 Blackwell Publishing Ltd.

  8. Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

    PubMed

    Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Wang, Xiaomei; Wang, Cong

    2017-01-01

    Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus .

  9. Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening

    PubMed Central

    Harini, K.; Sowdhamini, Ramanathan

    2015-01-01

    Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors. PMID:26221959

  10. The CC chemokine receptor 5 regulates olfactory and social recognition in mice.

    PubMed

    Kalkonde, Y V; Shelton, R; Villarreal, M; Sigala, J; Mishra, P K; Ahuja, S S; Barea-Rodriguez, E; Moretti, P; Ahuja, S K

    2011-12-01

    Chemokines are chemotactic cytokines that regulate cell migration and are thought to play an important role in a broad range of inflammatory diseases. The availability of chemokine receptor blockers makes them an important therapeutic target. In vitro, chemokines are shown to modulate neurotransmission. However, it is not very clear if chemokines play a role in behavior and cognition. Here we evaluated the role of CC chemokine receptor 5 (CCR5) in various behavioral tasks in mice using Wt (Ccr5⁺/⁺) and Ccr5-null (Ccr5⁻/⁻)mice. Ccr5⁻/⁻ mice showed enhanced social recognition. Administration of CC chemokine ligand 3 (CCL3), one of the CCR5-ligands, impaired social recognition. Since the social recognition task is dependent on the sense of olfaction, we tested olfactory recognition for social and non-social scents in these mice. Ccr5⁻/⁻ mice had enhanced olfactory recognition for both these scents indicating that enhanced performance in social recognition task could be due to enhanced olfactory recognition in these mice. Spatial memory and aversive memory were comparable in Wt and Ccr5⁻/⁻ mice. Collectively, these results suggest that chemokines/chemokine receptors might play an important role in olfactory recognition tasks in mice and to our knowledge represents the first direct demonstration of an in vivo role of CCR5 in modulating social behavior in mice. These studies are important as CCR5 blockers are undergoing clinical trials and can potentially modulate behavior. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones.

    PubMed

    Ahuja, Gaurav; Reichel, Vera; Kowatschew, Daniel; Syed, Adnan S; Kotagiri, Aswani Kumar; Oka, Yuichiro; Weth, Franco; Korsching, Sigrun I

    2018-05-23

    The sense of smell is unrivaled in terms of molecular complexity of its input channels. Even zebrafish, a model vertebrate system in many research fields including olfaction, possesses several hundred different olfactory receptor genes, organized in four different gene families. For one of these families, the initially discovered odorant receptors proper, segregation of expression into distinct spatial subdomains within a common sensory surface has been observed both in teleost fish and in mammals. However, for the remaining three families, little to nothing was known about their spatial coding logic. Here we wished to investigate, whether the principle of spatial segregation observed for odorant receptors extends to another olfactory receptor family, the V2R-related OlfC genes. Furthermore we thought to examine, how expression of OlfC genes is integrated into expression zones of odorant receptor genes, which in fish share a single sensory surface with OlfC genes. To select representative genes, we performed a comprehensive phylogenetic study of the zebrafish OlfC family, which identified a novel OlfC gene, reduced the number of pseudogenes to 1, and brought the total family size to 60 intact OlfC receptors. We analyzed the spatial pattern of OlfC-expressing cells for seven representative receptors in three dimensions (height within the epithelial layer, horizontal distance from the center of the olfactory organ, and height within the olfactory organ). We report non-random distributions of labeled neurons for all OlfC genes analysed. Distributions for sparsely expressed OlfC genes are significantly different from each other in nearly all cases, broad overlap notwithstanding. For two of the three coordinates analyzed, OlfC expression zones are intercalated with those of odorant receptor zones, whereas in the third dimension some segregation is observed. Our results show that V2R-related OlfC genes follow the same spatial logic of expression as odorant receptors and

  12. Odorant-stimulated phosphoinositide signaling in mammalian olfactory receptor neurons

    PubMed Central

    Klasen, K.; Corey, E.A.; Kuck, F.; Wetzel, C.H.; Hatt, H.; Ache, B.W.

    2009-01-01

    Recent evidence has revived interest in the idea that phosphoinositides (PIs) may play a role in signal transduction in mammalian olfactory receptor neurons (ORNs). To provide direct evidence that odorants indeed activate PI signaling in ORNs, we used adenoviral vectors carrying two different fluorescently tagged probes, the pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ1) and the general receptor of phosphoinositides (GRP1), to monitor PI activity in the dendritic knobs of ORNs in vivo. Odorants mobilized PI(4,5)P2/IP3 and PI(3,4,5)P3, the substrates and products of PLC and PI3K. We then measured odorant activation of PLC and PI3K in olfactory ciliary-enriched membranes in vitro using a phospholipid overlay assay and ELISAs. Odorants activated both PLC and PI3K in the olfactory cilia within 2 sec of odorant stimulation. Odorant-dependent activation of PLC and PI3K in the olfactory epithelium could be blocked by enzyme-specific inhibitors. Odorants activated PLC and PI3K with partially overlapping specificity. These results provide direct evidence that odorants indeed activate PI signaling in mammalian ORNs in a manner that is consistent with the idea that PI signaling plays a role in olfactory transduction. PMID:19781634

  13. Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb

    PubMed Central

    RASH, JOHN E.; DAVIDSON, KIMBERLY G. V.; KAMASAWA, NAOMI; YASUMURA, THOMAS; KAMASAWA, MASAMI; ZHANG, CHUNBO; MICHAELS, ROBIN; RESTREPO, DIEGO; OTTERSEN, OLE P.; OLSON, CARL O.; NAGY, JAMES I.

    2006-01-01

    Odorant/receptor binding and initial olfactory information processing occurs in olfactory receptor neurons (ORNs) within the olfactory epithelium. Subsequent information coding involves high-frequency spike synchronization of paired mitral/tufted cell dendrites within olfactory bulb (OB) glomeruli via positive feedback between glutamate receptors and closely-associated gap junctions. With mRNA for connexins Cx36, Cx43 and Cx45 detected within ORN somata and Cx36 and Cx43 proteins reported in ORN somata and axons, abundant gap junctions were proposed to couple ORNs. We used freeze-fracture replica immunogold labeling (FRIL) and confocal immunofluorescence microscopy to examine Cx36, Cx43 and Cx45 protein in gap junctions in olfactory mucosa, olfactory nerve and OB in adult rats and mice and early postnatal rats. In olfactory mucosa, Cx43 was detected in gap junctions between virtually all intrinsic cell types except ORNs and basal cells; whereas Cx45 was restricted to gap junctions in sustentacular cells. ORN axons contained neither gap junctions nor any of the three connexins. In OB, Cx43 was detected in homologous gap junctions between almost all cell types except neurons and oligodendrocytes. Cx36 and, less abundantly, Cx45 were present in neuronal gap junctions, primarily at “mixed” glutamatergic/electrical synapses between presumptive mitral/tufted cell dendrites. Genomic analysis revealed multiple miRNA (micro interfering RNA) binding sequences in 3′-untranslated regions of Cx36, Cx43 and Cx45 genes, consistent with cell-type-specific post-transcriptional regulation of connexin synthesis. Our data confirm absence of gap junctions between ORNs, and support Cx36- and Cx45-containing gap junctions at glutamatergic mixed synapses between mitral/tufted cells as contributing to higher-order information coding within OB glomeruli. PMID:16841170

  14. Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor.

    PubMed

    Tillerson, Jennifer L; Caudle, W Michael; Parent, Jack M; Gong, C; Schallert, Timothy; Miller, Gary W

    2006-09-15

    Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.

  15. Olfactory receptor Olfr544 responding to azelaic acid regulates glucagon secretion in α-cells of mouse pancreatic islets.

    PubMed

    Kang, NaNa; Bahk, Young Yil; Lee, NaHye; Jae, YoonGyu; Cho, Yoon Hee; Ku, Cheol Ryong; Byun, Youngjoo; Lee, Eun Jig; Kim, Min-Soo; Koo, JaeHyung

    2015-05-08

    Olfactory receptors (ORs) are extensively expressed in olfactory as well as non-olfactory tissues. Although many OR transcripts are expressed in non-olfactory tissues, only a few studies demonstrate the functional role of ORs. Here, we verified that mouse pancreatic α-cells express potential OR-mediated downstream effectors. Moreover, high levels of mRNA for the olfactory receptors Olfr543, Olfr544, Olfr545, and Olfr1349 were expressed in α-cells as assessed using RNA-sequencing, microarray, and quantitative real-time RT-PCR analyses. Treatment with dicarboxylic acids (azelaic acid and sebacic acid) increased intracellular Ca(2+) mobilization in pancreatic α-cells. The azelaic acid-induced Ca(2+) response as well as glucagon secretion was concentration- and time-dependent manner. Olfr544 was expressed in α-cells, and the EC50 value of azelaic acid to Olfr544 was 19.97 μM, whereas Olfr545 did not respond to azelaic acid. Our findings demonstrate that Olfr544 responds to azelaic acid to regulate glucagon secretion through Ca(2+) mobilization in α-cells of the mouse pancreatic islets, suggesting that Olfr544 may be an important therapeutic target for metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Functional architecture of olfactory ionotropic glutamate receptors.

    PubMed

    Abuin, Liliane; Bargeton, Benoîte; Ulbrich, Maximilian H; Isacoff, Ehud Y; Kellenberger, Stephan; Benton, Richard

    2011-01-13

    Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here, we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed coreceptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into the use of IRs as genetically encoded chemical sensors. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Identification and Comparison of Candidate Olfactory Genes in the Olfactory and Non-Olfactory Organs of Elm Pest Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) Based on Transcriptome Analysis.

    PubMed

    Wang, Yinliang; Chen, Qi; Zhao, Hanbo; Ren, Bingzhong

    2016-01-01

    The leaf beetle Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) is a predominant forest pest that causes substantial damage to the lumber industry and city management. However, no effective and environmentally friendly chemical method has been discovered to control this pest. Until recently, the molecular basis of the olfactory system in A. quadriimpressum was completely unknown. In this study, antennae and leg transcriptomes were analyzed and compared using deep sequencing data to identify the olfactory genes in A. quadriimpressum. Moreover, the expression profiles of both male and female candidate olfactory genes were analyzed and validated by bioinformatics, motif analysis, homology analysis, semi-quantitative RT-PCR and RT-qPCR experiments in antennal and non-olfactory organs to explore the candidate olfactory genes that might play key roles in the life cycle of A. quadriimpressum. As a result, approximately 102.9 million and 97.3 million clean reads were obtained from the libraries created from the antennas and legs, respectively. Annotation led to 34344 Unigenes, which were matched to known proteins. Annotation data revealed that the number of genes in antenna with binding functions and receptor activity was greater than that of legs. Furthermore, many pathway genes were differentially expressed in the two organs. Sixteen candidate odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 34 odorant receptors (ORs), 20 inotropic receptors [1] and 2 sensory neuron membrane proteins (SNMPs) and their isoforms were identified. Additionally, 15 OBPs, 9 CSPs, 18 ORs, 6 IRs and 2 SNMPs were predicted to be complete ORFs. Using RT-PCR, RT-qPCR and homology analysis, AquaOBP1/2/4/7/C1/C6, AquaCSP3/9, AquaOR8/9/10/14/15/18/20/26/29/33, AquaIR8a/13/25a showed olfactory-specific expression, indicating that these genes might play a key role in olfaction-related behaviors in A. quadriimpressum such as foraging and seeking. AquaOBP4/C5, AquaOBP4/C5, AquaCSP7

  18. A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium

    PubMed Central

    Araneda, Ricardo C; Peterlin, Zita; Zhang, Xinmin; Chesler, Alex; Firestein, Stuart

    2004-01-01

    Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca2+ imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30μm). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing. PMID:14724183

  19. Detection of Volatile Indicators of Illicit Substances by the Olfactory Receptors of Drosophila melanogaster

    PubMed Central

    Marshall, Brenton; Warr, Coral G.

    2010-01-01

    Insects can detect a large range of odors with a numerically simple olfactory system that delivers high sensitivity and accurate discrimination. Therefore, insect olfactory receptors hold great promise as biosensors for detection of volatile organic chemicals in a range of applications. The array of olfactory receptor neurons of Drosophila melanogaster is rapidly becoming the best-characterized natural nose. We have investigated the suitability of Drosophila receptors as detectors for volatiles with applications in law enforcement, emergency response, and security. We first characterized responses of the majority of olfactory neuron types to a set of diagnostic odorants. Being thus able to correctly identify neurons, we then screened for responses from 38 different types of neurons to 35 agents. We identified 13 neuron types with responses to 13 agents. As individual Drosophila receptor genes have been mapped to neuron types, we can infer which genes confer responsiveness to the neurons. The responses were confirmed for one receptor by expressing it in a nonresponsive neuron. The fly olfactory system is mainly adapted to detect volatiles from fermenting fruits. However, our findings establish that volatiles associated with illicit substances, many of which are of nonnatural origin, are also detected by Drosophila receptors. PMID:20530374

  20. Efficient cell-free production of olfactory receptors: detergent optimization, structure, and ligand binding analyses.

    PubMed

    Kaiser, Liselotte; Graveland-Bikker, Johanna; Steuerwald, Dirk; Vanberghem, Mélanie; Herlihy, Kara; Zhang, Shuguang

    2008-10-14

    High-level production of membrane proteins, particularly of G protein-coupled receptors (GPCRs) in heterologous cell systems encounters a number of difficulties from their inherent hydrophobicity in their transmembrane domains, which frequently cause protein aggregation and cytotoxicity and thus reduce the protein yield. Recent advances in cell-free protein synthesis circumvent those problems to produce membrane proteins with a yield sometimes exceeding the cell-based approach. Here, we report cell-free production of a human olfactory receptor 17-4 (hOR17-4) using the wheat germ extract. Using the simple method, we also successful produced two additional olfactory receptors. To obtain soluble olfactory receptors and to increase yield, we directly added different detergents in varying concentrations to the cell-free reaction. To identify a purification buffer system that maintained the receptor in a nonaggregated form, we developed a method that uses small-volume size-exclusion column chromatography combined with rapid and sensitive dot-blot detection. Different buffer components including salt concentration, various detergents and detergent concentration, and reducing agent and its concentrations were evaluated for their ability to maintain the cell-free produced protein stable and nonaggregated. The purified olfactory receptor displays a typical a alpha-helical CD spectrum. Surface plasmon resonance measurements were used to show binding of a known ligand undecanal to hOR17-4. Our approach to produce a high yield of purified olfactory receptor is a milestone toward obtaining a large quantity of olfactory receptors for designing bionic sensors. Furthermore, this simple approach may be broadly useful not only for other classes of GPCRs but also for other membrane proteins.

  1. Efficient cell-free production of olfactory receptors: Detergent optimization, structure, and ligand binding analyses

    PubMed Central

    Kaiser, Liselotte; Graveland-Bikker, Johanna; Steuerwald, Dirk; Vanberghem, Mélanie; Herlihy, Kara; Zhang, Shuguang

    2008-01-01

    High-level production of membrane proteins, particularly of G protein-coupled receptors (GPCRs) in heterologous cell systems encounters a number of difficulties from their inherent hydrophobicity in their transmembrane domains, which frequently cause protein aggregation and cytotoxicity and thus reduce the protein yield. Recent advances in cell-free protein synthesis circumvent those problems to produce membrane proteins with a yield sometimes exceeding the cell-based approach. Here, we report cell-free production of a human olfactory receptor 17-4 (hOR17-4) using the wheat germ extract. Using the simple method, we also successful produced two additional olfactory receptors. To obtain soluble olfactory receptors and to increase yield, we directly added different detergents in varying concentrations to the cell-free reaction. To identify a purification buffer system that maintained the receptor in a nonaggregated form, we developed a method that uses small-volume size-exclusion column chromatography combined with rapid and sensitive dot-blot detection. Different buffer components including salt concentration, various detergents and detergent concentration, and reducing agent and its concentrations were evaluated for their ability to maintain the cell-free produced protein stable and nonaggregated. The purified olfactory receptor displays a typical a α-helical CD spectrum. Surface plasmon resonance measurements were used to show binding of a known ligand undecanal to hOR17-4. Our approach to produce a high yield of purified olfactory receptor is a milestone toward obtaining a large quantity of olfactory receptors for designing bionic sensors. Furthermore, this simple approach may be broadly useful not only for other classes of GPCRs but also for other membrane proteins. PMID:18840687

  2. Guidepost neurons for the lateral olfactory tract: expression of metabotropic glutamate receptor 1 and innervation by glutamatergic olfactory bulb axons.

    PubMed

    Hirata, Tatsumi; Kumada, Tatsuro; Kawasaki, Takahiko; Furukawa, Tomonori; Aiba, Atsu; Conquet, François; Saga, Yumiko; Fukuda, Atsuo

    2012-12-01

    The guidepost neurons for the lateral olfactory tract, which are called lot cells, are the earliest-generated neurons in the neocortex. They migrate tangentially and ventrally further down this tract, and provide scaffolding for the olfactory bulb axons projecting into this pathway. The molecular profiles of the lot cells are largely uncharacterized. We found that lot cells specifically express metabotropic glutamate receptor subtype-1 at a very early stage of development. This receptor is functionally competent and responds to a metabotropic glutamate receptor agonist with a transient increase in the intracellular calcium ion concentration. When the glutamatergic olfactory bulb axons were electrically stimulated, lot cells responded to the stimulation with a calcium increase mainly via ionotropic glutamate receptors, suggesting potential neurotransmission between the axons and lot cells during early development. Together with the finding that lot cells themselves are glutamatergic excitatory neurons, our results provide another notable example of precocious interactions between the projecting axons and their intermediate targets. Copyright © 2012 Wiley Periodicals, Inc.

  3. Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb

    PubMed Central

    Ma, Jie; Lowe, Graeme

    2007-01-01

    Glomeruli are functional units of the olfactory bulb responsible for early processing of odor information encoded by single olfactory receptor genes. Glomerular neural circuitry includes numerous external tufted (ET) cells whose rhythmic burst firing may mediate synchronization of bulbar activity with the inhalation cycle. Bursting is entrained by glutamatergic input from olfactory nerve terminals, so specific properties of ionotropic glutamate receptors on ET cells are likely to be important determinants of olfactory processing. Particularly intriguing is recent evidence that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors of juxta-glomerular neurons may permeate calcium. This could provide a novel pathway for regulating ET cell signaling. We tested the hypothesis that ET cells express functional calcium-permeable AMPA receptors. In rat olfactory bulb slices, excitatory postsynaptic currents (EPSCs) in ET cells were evoked by olfactory nerve shock, and by uncaging glutamate. We found attenuation of AMPA/kainate EPSCs by 1-naphthyl acetyl-spermine (NAS), an open-channel blocker specific for calcium permeable AMPA receptors. Cyclothiazide strongly potentiated EPSCs, indicating a major contribution from AMPA receptors. The current-voltage (I-V) relation of uncaging EPSCs showed weak inward rectification which was lost after > ~ 10 min of whole-cell dialysis, and was absent in NAS. In kainate-stimulated slices, Co2+ ions permeated cells of the glomerular layer. Large AMPA EPSCs were accompanied by fluorescence signals in fluo-4 loaded cells, suggesting calcium permeation. Depolarizing pulses evoked slow tail currents with pharmacology consistent with involvement of calcium permeable AMPA autoreceptors. Tail currents were abolished by Cd2+ and NBQX, and were sensitive to NAS block. Glutamate autoreceptors were confirmed by uncaging intracellular calcium to evoke a large inward current. Our results provide evidence that calcium permeable AMPA

  4. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    PubMed

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J; Jerabek-Willemsen, Moran; Duhr, Stefan; Luo, Yuan; Braun, Dieter; Zhang, Shuguang

    2011-01-01

    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  5. Designer Lipid-Like Peptides: A Class of Detergents for Studying Functional Olfactory Receptors Using Commercial Cell-Free Systems

    PubMed Central

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B.; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J.; Jerabek-Willemsen, Moran; Duhr, Stefan; Luo, Yuan; Braun, Dieter; Zhang, Shuguang

    2011-01-01

    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins. PMID:22132066

  6. Elimination of a ligand gating site generates a supersensitive olfactory receptor.

    PubMed

    Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I

    2016-06-21

    Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.

  7. Elimination of a ligand gating site generates a supersensitive olfactory receptor

    PubMed Central

    Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I.

    2016-01-01

    Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors. PMID:27323929

  8. Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

    PubMed Central

    Tabor, Rico; Friedrich, Rainer W.

    2008-01-01

    Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb. PMID:18183297

  9. Cyclic nucleotide- and inositol phosphate-gated ion channels in lobster olfactory receptor neurons.

    PubMed Central

    Hatt, H; Ache, B W

    1994-01-01

    The idea of having two second messenger pathways in olfaction, one mediated by cAMP and the other by inositol 1,4,5-trisphosphate, is supported by evidence that both second messengers directly activate distinct ion channels in the outer dendrite of lobster olfactory receptor neurons. Evidence that both types of second messenger-gated channels can occur in the same patch of membrane suggests that channels of both types can be expressed in one neuron. Evidence of more than one type of inositol phosphate-gated channel in this highly specialized region of the neuron furthers the idea that the output of individual olfactory receptor cells is regulated through multiple effectors and allows that effector diversity may contribute to functional diversity among olfactory receptor cells. Images PMID:7517547

  10. Expressional and functional interactions of two Apis cerana cerana olfactory receptors.

    PubMed

    Guo, Lina; Zhao, Huiting; Jiang, Yusuo

    2018-01-01

    Apis cerana cerana relies on its sensitive olfactory system to perform foraging activities in the surrounding environment. Olfactory receptors (ORs) are a primary requirement for odorant recognition and coding. However, the molecular recognition of volatile compounds with ORs in A. cerana cerana is still not clear. Hence, in the present study, we achieved transient transfection and cell surface expression of A. cerana cerana ORs (AcerOr1 and AcerOr2; AcerOr2 is orthologous to the co-receptor) in Spodoptera frugiperda (Sf9) cells. AcerOr2 narrowly responded to N-(4-ethylphenyl)-2-((4-ethyl-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl) thio) acetamide (VUAA1), whereas AcerOr1 was sensitive to eugenol, lauric acid, ocimene, 1-nonanol, linolenic acid, hexyl acetate, undecanoic acid, 1-octyl alcohol, and nerol. Of the compounds tested, AcerOr1 showed the highest sensitivity to these odorants with EC 50 values of 10 -7 and 10 -8 M, and AcerOr2 recognized VUAA1 with higher sensitivity [EC 50 = (6.621 ± 0.26) × 10 -8 ]. These results indicate that AcerOr2 is an essential gene for olfactory signaling, and AcerOr1 is a broadly tuned receptor. We discovered ligands that were useful for probing receptor activity during odor stimulation and validated three of them by electroantennography. The response increased with concentration of the odorant. The present study provides insight into the mechanism of olfactory discrimination in A. cerana cerana .

  11. Positive selection moments identify potential functional residues in human olfactory receptors

    NASA Technical Reports Server (NTRS)

    Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

    1996-01-01

    Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

  12. Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid.

    PubMed

    Thach, Trung Thanh; Hong, Yu-Jung; Lee, Sangho; Lee, Sung-Joon

    2017-04-01

    The mouse olfactory receptor Olfr544 is expressed in several non-olfactory tissues and has been suggested as a functional receptor regulating different signaling pathways. However, the molecular interaction between Olfr544 and its natural ligand, azelaic acid (AzA), remains poorly characterized, primarily due to difficulties in the heterologous expression of the receptor protein on the cell membrane and lack of entire protein structure. In this report, we describe the molecular determinants of Olfr544 activation by AzA. N-terminal lucy-flag-rho tag ensured the heterologous expression of Olfr544 on the Hana3A cell surface. Molecular modeling and docking combined with mutational analysis identified amino acid residues in the Olfr544 for the interaction with AzA. Our data demonstrated that the Y109 residue in transmembrane helix 3 forms a hydrogen bond with AzA, which is crucial for the receptor-ligand interaction and activation. Y109 is required for the Olfr544 activation by AzA which, in turn, stimulates the Olfr544-dependent CREB-PGC-1α signaling axis and is followed by the induction of mitochondrial biogenesis in Olfr544 wild-type transfected Hana3A cells, but not in mock or Y109A mutant transfected cells. Collectively, these data indicated that a hydrogen bond between Y109 residue and AzA is a major determinant of the Olfr544-AzA interaction and activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

    ERIC Educational Resources Information Center

    Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

    2015-01-01

    Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

  14. Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor.

    PubMed

    Pozharskaya, Tatyana; Liang, Jonathan; Lane, Andrew P

    2013-09-01

    Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed. IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-α expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice. TNFR2 is the minor receptor for TNF-α, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS. © 2013 ARS-AAOA, LLC.

  15. Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies.

    PubMed

    Kelling, F J; Ialenti, F; Den Otter, C J

    2002-06-01

    The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross-adaptation and cross-sensitization between a background odour of (+/-)-1-octen-3-ol and pulses of (+/-)-1-octen-3-ol, 2-pentanone and R-(+)-limonene can occur, confirming that olfactory receptor cells are sensitive to different odours. Background odour can increase the responses to low concentration odour pulses and decrease the responses to higher concentration odour pulses. It is suggested that background odour has a larger effect on olfactory receptor cells that respond with a tonic increase of spike frequency, giving information about the level of odour concentration, i.e. the 'static' environment. Cells that respond in a phasic way only provide information on the dynamics of the olfactory environment.

  16. Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance.

    PubMed

    Knott, Thomas K; Madany, Pasil A; Faden, Ashley A; Xu, Mei; Strotmann, Jörg; Henion, Timothy R; Schwarting, Gerald A

    2012-07-04

    The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2(-/-) mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2(-/-) neurons. Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2(-/-) mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2(-/-) olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2(-/-) mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2(-/-) olfactory neurons. Results presented here show that many odorant receptors are under-expressed in β3GnT2(-/-) mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2(-/-) mice exhibit a relatively small deficit in

  17. Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

    PubMed Central

    Cook, Brian L.; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P.; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

    2009-01-01

    Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be ≈50% α-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices. PMID:19581598

  18. Large-scale production and study of a synthetic G protein-coupled receptor: human olfactory receptor 17-4.

    PubMed

    Cook, Brian L; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

    2009-07-21

    Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be approximately 50% alpha-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.

  19. Olfactory Receptor Subgenomes Linked with Broad Ecological Adaptations in Sauropsida.

    PubMed

    Khan, Imran; Yang, Zhikai; Maldonado, Emanuel; Li, Cai; Zhang, Guojie; Gilbert, M Thomas P; Jarvis, Erich D; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2015-11-01

    Olfactory receptors (ORs) govern a prime sensory function. Extant birds have distinct olfactory abilities, but the molecular mechanisms underlining diversification and specialization remain mostly unknown. We explored OR diversity in 48 phylogenetic and ecologically diverse birds and 2 reptiles (alligator and green sea turtle). OR subgenomes showed species- and lineage-specific variation related with ecological requirements. Overall 1,953 OR genes were identified in reptiles and 16,503 in birds. The two reptiles had larger OR gene repertoires (989 and 964 genes, respectively) than birds (182-688 genes). Overall, birds had more pseudogenes (7,855) than intact genes (1,944). The alligator had significantly more functional genes than sea turtle, likely because of distinct foraging habits. We found rapid species-specific expansion and positive selection in OR14 (detects hydrophobic compounds) in birds and in OR51 and OR52 (detect hydrophilic compounds) in sea turtle, suggestive of terrestrial and aquatic adaptations, respectively. Ecological partitioning among birds of prey, water birds, land birds, and vocal learners showed that diverse ecological factors determined olfactory ability and influenced corresponding olfactory-receptor subgenome. OR5/8/9 was expanded in predatory birds and alligator, suggesting adaptive specialization for carnivory. OR families 2/13, 51, and 52 were correlated with aquatic adaptations (water birds), OR families 6 and 10 were more pronounced in vocal-learning birds, whereas most specialized land birds had an expanded OR family 14. Olfactory bulb ratio (OBR) and OR gene repertoire were correlated. Birds that forage for prey (carnivores/piscivores) had relatively complex OBR and OR gene repertoires compared with modern birds, including passerines, perhaps due to highly developed cognitive capacities facilitating foraging innovations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and

  20. Effect of non-selective dopaminergic receptor agonist on disrupted maternal behavior in olfactory bulbectomized mice.

    PubMed

    Sato, Atsushi; Nakagawasai, Osamu; Tan-No, Koichi; Onogi, Hiroshi; Niijima, Fukie; Tadano, Takeshi

    2010-07-11

    Olfactory bulbectomy (OBX) animals are considered a putative model of depression that produces behavioral, physiological, and neurochemical alterations resembling clinical depression. Depression is a critical cause of child abuse and neglect, and it has been reported that maternal behavior involves dopaminergic neurons of the mesolimbic pathway. In this study, we investigated the effect of apomorphine, a non-selective dopaminergic receptor agonist, on maternal behavior to examine the influence of activated brain dopaminergic function in OBX mice. In addition, we conducted the sucrose preference test to examine the reward system which has a critical relationship to mesolimbic dopaminergic function and maternal behavior. Maternal behavior was observed on postnatal day (PND) 0 and 4. OBX female mice showed a reduction in sucrose preference 2 weeks post surgery. OBX dams showed maternal behavior deficits on PND 0, and these deficits were ameliorated by administration of apomorphine. These results suggest that maternal behavior deficits in OBX dams may involve brain hypodopaminergic function in the central nervous system induced by OBX. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Evidence for increased olfactory receptor gene repertoire size in two nocturnal bird species with well-developed olfactory ability

    PubMed Central

    Steiger, Silke S; Fidler, Andrew E; Kempenaers, Bart

    2009-01-01

    Background In vertebrates, the molecular basis of the sense of smell is encoded by members of a large gene family, namely olfactory receptor (OR) genes. Both the total number of OR genes and the proportion of intact OR genes in a genome may indicate the importance of the sense of smell for an animal. There is behavioral, physiological, and anatomical evidence that some bird species, in particular nocturnal birds, have a well developed sense of smell. Therefore, we hypothesized that nocturnal birds with good olfactory abilities have evolved (i) more OR genes and (ii) more intact OR genes than closely related and presumably less 'olfaction-dependent' day-active avian taxa. Results We used both non-radioactive Southern hybridization and PCR with degenerate primers to investigate whether two nocturnal bird species that are known to rely on olfactory cues, the brown kiwi (Apteryx australis) and the kakapo (Strigops habroptilus), have evolved a larger OR gene repertoire than their day-active, closest living relatives (for kiwi the emu Dromaius novaehollandiae, rhea Rhea americana, and ostrich Struthio camelus and for kakapo the kaka Nestor meridionalis and kea Nestor notabilis). We show that the nocturnal birds did not have a significantly higher proportion of intact OR genes. However, the estimated total number of OR genes was larger in the two nocturnal birds than in their relatives. Conclusion Our results suggest that ecological niche adaptations such as daily activity patterns may have shaped avian OR gene repertoires. PMID:19467156

  2. Prior activity of olfactory receptor neurons is required for proper sensory processing and behavior in Drosophila larvae.

    PubMed

    Utashiro, Nao; Williams, Claire R; Parrish, Jay Z; Emoto, Kazuo

    2018-06-05

    Animal responses to their environment rely on activation of sensory neurons by external stimuli. In many sensory systems, however, neurons display basal activity prior to the external stimuli. This prior activity is thought to modulate neural functions, yet its impact on animal behavior remains elusive. Here, we reveal a potential role for prior activity in olfactory receptor neurons (ORNs) in shaping larval olfactory behavior. We show that prior activity in larval ORNs is mediated by the olfactory receptor complex (OR complex). Mutations of Orco, an odorant co-receptor required for OR complex function, cause reduced attractive behavior in response to optogenetic activation of ORNs. Calcium imaging reveals that Orco mutant ORNs fully respond to optogenetic stimulation but exhibit altered temporal patterns of neural responses. These findings together suggest a critical role for prior activity in information processing upon ORN activation in Drosophila larvae, which in turn contributes to olfactory behavior control.

  3. Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance

    PubMed Central

    2012-01-01

    Background The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2−/− mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2−/− neurons. Results Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2−/− mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2−/− olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2−/− mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2−/− olfactory neurons. Conclusions Results presented here show that many odorant receptors are under-expressed in β3GnT2−/− mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2

  4. Activation of EGF Receptor Mediates Receptor Axon Sorting and Extension in the Developing Olfactory System of the Moth Manduca sexta

    PubMed Central

    Gibson, Nicholas J.; Tolbert, Leslie P.

    2008-01-01

    During development of the adult olfactory system of the moth Manduca sexta, olfactory receptor neurons extend axons from the olfactory epithelium in the antenna into the brain. As they arrive at the brain, interactions with centrally-derived glial cells cause axons to sort and fasciculate with other axons destined to innervate the same glomeruli. Here we report studies that indicate that activation of the epidermal growth factor receptor (EGFR) is involved in axon ingrowth and targeting. Blocking the EGFR kinase domain pharmacologically leads to stalling of many axons in the sorting zone and nerve layer, as well as abnormal axonal fasciculation in the sorting zone. We also find that neuroglian, an IgCAM known to activate the EGFR through homophilic interactions in other systems, is transiently present on olfactory receptor neuron axons and on glia during the critical stages of the sorting process. The neuroglian is resistant to extraction with Triton X-100 in the sorting zone and nerve layer, possibly indicating its stabilization by homophilic binding in these regions. Our results suggest a mechanism whereby neuroglian molecules on axons and possibly sorting zone glia bind homophilically, leading to activation of EGFRs with subsequent effects on axon sorting, pathfinding, and extension, and glomerulus development. PMID:16498681

  5. Penguins reduced olfactory receptor genes common to other waterbirds

    PubMed Central

    Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

    2016-01-01

    The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins. PMID:27527385

  6. Co-localization of TRPV2 and insulin-like growth factor-I receptor in olfactory neurons in adult and fetal mouse.

    PubMed

    Matsui, Hitoshi; Noguchi, Tomohiro; Takakusaki, Kaoru; Kashiwayanagi, Makoto

    2014-01-01

    TRPV2, a member of the transient receptor potential family, has been isolated as a capsaicin-receptor homolog and is thought to respond to noxious heat. Here we show that TRPV2 mRNA is predominantly expressed in the subpopulation of olfactory sensory neurons (OSNs). We carried out histochemical analyses of TRPV2 and insulin-like growth factor-I receptor (IGF-IR) using in situ hybridization and immunofluorescence in the adult olfactory system. In olfactory mucosa, intensive TRPV2 immunostaining was observed at the olfactory axon bundles but not at the soma. TRPV2-positive labeling was preferentially found in the olfactory nerve layer in the olfactory bulb (OB). Furthermore, we demonstrated that a positive signal for IGF-IR mRNA was detected in OSNs expressing TRPV2 mRNA. In embryonic stages, TRPV2 immunoreactivity was observed on axon bundles of developing OSNs in the nasal region starting from 12.5 d of gestation and through fetal development. Observations in this study suggest that TRPV2 coupled with IGF-IR localizes to growing olfactory axons in the OSNs.

  7. Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

    PubMed

    Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

    2017-11-07

    Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

  8. Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats

    PubMed Central

    Wu, Chunyan; Hwang, Su Hyeon; Jia, Yaoyao; Choi, Joobong; Kim, Yeon-Ji; Choi, Dahee; Pathiraja, Duleepa; Choi, In-Geol; Koo, Seung-Hoi

    2017-01-01

    Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-α and genes required for FAO in the liver and induced the expression of PPAR-γ coactivator 1-α (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544–/– mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT. PMID:28990936

  9. Molecular Cooperativity Governs Diverse and Monoallelic Olfactory Receptor Expression

    NASA Astrophysics Data System (ADS)

    Xing, Jianhua; Tian, Xiaojun; Zhang, Hang; Sannerud, Jens

    Multiple-objective optimization is common in biological systems. In the mammalian olfactory system, each sensory neuron stochastically expresses only one out of up to thousands of olfactory receptor (OR) gene alleles; at organism level the types of expressed ORs need to be maximized. The molecular mechanism of this Nobel-Prize winning puzzle remains unresolved after decades of extensive studies. Existing models focus only on monoallele activation, and cannot explain recent observations in mutants, especially the reduced global diversity of expressed ORs in G9a/GLP knockouts. In this work we integrated existing information on OR expression, and proposed an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic and enhancer competition coupled to a negative feedback loop. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression. The model is validated by several experimental results, and particularly underscores cooperativity and synergy as a general design principle of multi-objective optimization in biology. The work is supported by the NIGMS/DMS Mathematical Biology program.

  10. The number of functional olfactory receptor genes and the relative size of olfactory brain structures are poor predictors of olfactory discrimination performance with enantiomers.

    PubMed

    Laska, Matthias; Genzel, Daria; Wieser, Alexandra

    2005-02-01

    The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.

  11. Voltage-gated currents in identified rat olfactory receptor neurons.

    PubMed

    Trombley, P Q; Westbrook, G L

    1991-02-01

    Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act

  12. Towards structural models of molecular recognition in olfactory receptors.

    PubMed

    Afshar, M; Hubbard, R E; Demaille, J

    1998-02-01

    The G protein coupled receptors (GPCR) are an important class of proteins that act as signal transducers through the cytoplasmic membrane. Understanding the structure and activation mechanism of these proteins is crucial for understanding many different aspects of cellular signalling. The olfactory receptors correspond to the largest family of GPCRs. Very little is known about how the structures of the receptors govern the specificity of interaction which enables identification of particular odorant molecules. In this paper, we review recent developments in two areas of molecular modelling: methods for modelling the configuration of trans-membrane helices and methods for automatic docking of ligands into receptor structures. We then show how a subset of these methods can be combined to construct a model of a rat odorant receptor interacting with lyral for which experimental data are available. This modelling can help us make progress towards elucidating the specificity of interactions between receptors and odorant molecules.

  13. Activation of epidermal growth factor receptor mediates receptor axon sorting and extension in the developing olfactory system of the moth Manduca sexta.

    PubMed

    Gibson, Nicholas J; Tolbert, Leslie P

    2006-04-10

    During development of the adult olfactory system of the moth Manduca sexta, olfactory receptor neurons extend axons from the olfactory epithelium in the antenna into the brain. As they arrive at the brain, interactions with centrally derived glial cells cause axons to sort and fasciculate with other axons destined to innervate the same glomeruli. Here we report studies indicating that activation of the epidermal growth factor receptor (EGFR) is involved in axon ingrowth and targeting. Blocking the EGFR kinase domain pharmacologically leads to stalling of many axons in the sorting zone and nerve layer as well as abnormal axonal fasciculation in the sorting zone. We also find that neuroglian, an IgCAM known to activate the EGFR through homophilic interactions in other systems, is transiently present on olfactory receptor neuron axons and on glia during the critical stages of the sorting process. The neuroglian is resistant to extraction with Triton X-100 in the sorting zone and nerve layer, possibly indicating its stabilization by homophilic binding in these regions. Our results suggest a mechanism whereby neuroglian molecules on axons and possibly sorting zone glia bind homophilically, leading to activation of EGFRs, with subsequent effects on axon sorting, pathfinding, and extension, and glomerulus development. Copyright 2006 Wiley-Liss, Inc.

  14. Underlying mathematics in diversification of human olfactory receptors in different loci.

    PubMed

    Hassan, Sk Sarif; Choudhury, Pabitra Pal; Goswami, Arunava

    2013-12-01

    As per conservative estimate, approximately 51-105 Olfactory Receptors (ORs) loci are present in human genome occurring in clusters. These clusters are apparently unevenly spread as mosaics over 21 pairs of human chromosomes. Olfactory Receptor (OR) gene families which are thought to have expanded for the need to provide recognition capability for a huge number of pure and complex odorants, form the largest known multigene family in the human genome. Recent studies have shown that 388 full length and 414 OR pseudo-genes are present in these OR genomic clusters. In this paper, the authors report a classification method for all human ORs based on their sequential quantitative information like presence of poly strings of nucleotides bases, long range correlation and so on. An L-System generated sequence has been taken as an input into a star-model of specific subfamily members and resultant sequence has been mapped to a specific OR based on the classification scheme using fractal parameters like Hurst exponent and fractal dimensions.

  15. Avian olfactory receptor gene repertoires: evidence for a well-developed sense of smell in birds?

    PubMed Central

    Steiger, Silke S; Fidler, Andrew E; Valcu, Mihai; Kempenaers, Bart

    2008-01-01

    Among vertebrates, the sense of smell is mediated by olfactory receptors (ORs) expressed in sensory neurons within the olfactory epithelium. Comparative genomic studies suggest that the olfactory acuity of mammalian species correlates positively with both the total number and the proportion of functional OR genes encoded in their genomes. In contrast to mammals, avian olfaction is poorly understood, with birds widely regarded as relying primarily on visual and auditory inputs. Here, we show that in nine bird species from seven orders (blue tit, Cyanistes caeruleus; black coucal, Centropus grillii; brown kiwi, Apteryx australis; canary, Serinus canaria; galah, Eolophus roseicapillus; red jungle fowl, Gallus gallus; kakapo, Strigops habroptilus; mallard, Anas platyrhynchos; snow petrel, Pagodroma nivea), the majority of amplified OR sequences are predicted to be from potentially functional genes. This finding is somewhat surprising as one previous report suggested that the majority of OR genes in an avian (red jungle fowl) genomic sequence are non-functional pseudogenes. We also show that it is not the estimated proportion of potentially functional OR genes, but rather the estimated total number of OR genes that correlates positively with relative olfactory bulb size, an anatomical correlate of olfactory capability. We further demonstrate that all the nine bird genomes examined encode OR genes belonging to a large gene clade, termed γ-c, the expansion of which appears to be a shared characteristic of class Aves. In summary, our findings suggest that olfaction in birds may be a more important sense than generally believed. PMID:18628122

  16. Morphological study on the olfactory systems of the snapping turtle, Chelydra serpentina.

    PubMed

    Nakamuta, Nobuaki; Nakamuta, Shoko; Kato, Hideaki; Yamamoto, Yoshio

    2016-06-01

    In this study, the olfactory system of a semi-aquatic turtle, the snapping turtle, has been morphologically investigated by electron microscopy, immunohistochemistry, and lectin histochemistry. The nasal cavity of snapping turtle was divided into the upper and lower chambers, lined by the sensory epithelium containing ciliated and non-ciliated olfactory receptor neurons, respectively. Each neuron expressed both Gαolf, the α-subunit of G-proteins coupling to the odorant receptors, and Gαo, the α-subunit of G-proteins coupling to the type 2 vomeronasal receptors. The axons originating from the upper chamber epithelium projected to the ventral part of the olfactory bulb, while those from the lower chamber epithelium to the dorsal part of the olfactory bulb. Despite the identical expression of G-protein α-subunits in the olfactory receptor neurons, these two projections were clearly distinguished from each other by the differential expression of glycoconjugates. In conclusion, these data indicate the presence of two types of olfactory systems in the snapping turtle. Topographic arrangement of the upper and lower chambers and lack of the associated glands in the lower chamber epithelium suggest their possible involvement in the detection of odorants: upper chamber epithelium in the air and the lower chamber epithelium in the water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A competitive binding model predicts the response of mammalian olfactory receptors to mixtures

    NASA Astrophysics Data System (ADS)

    Singh, Vijay; Murphy, Nicolle; Mainland, Joel; Balasubramanian, Vijay

    Most natural odors are complex mixtures of many odorants, but due to the large number of possible mixtures only a small fraction can be studied experimentally. To get a realistic understanding of the olfactory system we need methods to predict responses to complex mixtures from single odorant responses. Focusing on mammalian olfactory receptors (ORs in mouse and human), we propose a simple biophysical model for odor-receptor interactions where only one odor molecule can bind to a receptor at a time. The resulting competition for occupancy of the receptor accounts for the experimentally observed nonlinear mixture responses. We first fit a dose-response relationship to individual odor responses and then use those parameters in a competitive binding model to predict mixture responses. With no additional parameters, the model predicts responses of 15 (of 18 tested) receptors to within 10 - 30 % of the observed values, for mixtures with 2, 3 and 12 odorants chosen from a panel of 30. Extensions of our basic model with odorant interactions lead to additional nonlinearities observed in mixture response like suppression, cooperativity, and overshadowing. Our model provides a systematic framework for characterizing and parameterizing such mixing nonlinearities from mixture response data.

  18. Conventional and Non-Conventional Drosophila Toll Signaling

    PubMed Central

    Lindsay, Scott A.; Wasserman, Steven A.

    2013-01-01

    The discovery of Toll in Drosophila and of the remarkable conservation in pathway composition and organization catalyzed a transformation in our understanding of innate immune recognition and response. At the center of that picture is a cascade of interactions in which specific microbial cues activate Toll receptors, which then transmit signals driving transcription factor nuclear localization and activity. Experiments gave substance to the vision of pattern recognition receptors, linked phenomena in development, gene regulation, and immunity into a coherent whole, and revealed a rich set of variations for identifying non-self and responding effectively. More recently, research in Drosophila has illuminated the positive and negative regulation of Toll activation, the organization of signaling events at and beneath membranes, the sorting of information flow, and the existence of non-conventional signaling via Toll-related receptors. Here, we provide an overview of the Toll pathway of flies and highlight these ongoing realms of research. PMID:23632253

  19. Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila

    PubMed Central

    Iyengar, Atulya; Chakraborty, Tuhin Subhra; Goswami, Sarit Pati; Wu, Chun-Fang; Siddiqi, Obaid

    2010-01-01

    Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen–Shannon divergence (DJS) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron. PMID:20448199

  20. Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila.

    PubMed

    Iyengar, Atulya; Chakraborty, Tuhin Subhra; Goswami, Sarit Pati; Wu, Chun-Fang; Siddiqi, Obaid

    2010-05-25

    Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen-Shannon divergence (D(JS)) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron.

  1. NMDA-receptor dependent synaptic activation of TRPC channels in olfactory bulb granule cells

    PubMed Central

    Stroh, Olga; Freichel, Marc; Kretz, Oliver; Birnbaumer, Lutz; Hartmann, Jana; Egger, Veronica

    2012-01-01

    TRPC channels are widely expressed throughout the nervous system including the olfactory bulb where their function is largely unknown. Here we describe their contribution to central synaptic processing at the reciprocal mitral and tufted cell - granule cell microcircuit, the most abundant synapse of the mammalian olfactory bulb. Suprathreshold activation of the synapse causes sodium action potentials in mouse granule cells and a subsequent long-lasting depolarization (LLD) linked to a global dendritic postsynaptic calcium signal recorded with two-photon laser scanning microscopy. These signals are not observed after action potentials evoked by current injection in the same cells. The LLD persists in the presence of group I metabotropic glutamate receptor antagonists but is entirely absent from granule cells deficient for the NMDA receptor subunit NR1. Moreover, both depolarization and Ca2+ rise are sensitive to the blockade of NMDA receptors. The LLD and the accompanying Ca2+ rise are also absent in granule cells from mice deficient for both TRPC channel subtypes 1 and 4, whereas the deletion of either TRPC1 or TRPC4 results in only a partial reduction of the LLD. Recordings from mitral cells in the absence of both subunits reveal a reduction of asynchronous neurotransmitter release from the granule cells during recurrent inhibition. We conclude that TRPC1 and TRPC4 can be activated downstream of NMDA receptor activation and contribute to slow synaptic transmission in the olfactory bulb, including the calcium dynamics required for asynchronous release from the granule cell spine. PMID:22539836

  2. Spontaneous olfactory receptor neuron activity determines follower cell response properties

    PubMed Central

    Joseph, Joby; Dunn, Felice A.; Stopfer, Mark

    2012-01-01

    Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872

  3. Canine olfactory receptor gene polymorphism and its relation to odor detection performance by sniffer dogs.

    PubMed

    Lesniak, Anna; Walczak, Marta; Jezierski, Tadeusz; Sacharczuk, Mariusz; Gawkowski, Maciej; Jaszczak, Kazimierz

    2008-01-01

    The outstanding sensitivity of the canine olfactory system has been acknowledged by using sniffer dogs in military and civilian service for detection of a variety of odors. It is hypothesized that the canine olfactory ability is determined by polymorphisms in olfactory receptor (OR) genes. We investigated 5 OR genes for polymorphic sites which might affect the olfactory ability of service dogs in different fields of specific substance detection. All investigated OR DNA sequences proved to have allelic variants, the majority of which lead to protein sequence alteration. Homozygous individuals at 2 gene loci significantly differed in their detection skills from other genotypes. This suggests a role of specific alleles in odor detection and a linkage between single-nucleotide polymorphism and odor recognition efficiency.

  4. Deletion of the Bombyx mori odorant receptor co-receptor (BmOrco) impairs olfactory sensitivity in silkworms.

    PubMed

    Liu, Qun; Liu, Wei; Zeng, Baosheng; Wang, Guirong; Hao, Dejun; Huang, Yongping

    2017-07-01

    Olfaction plays an essential role in many important insect behaviors such as feeding and reproduction. To detect olfactory stimuli, an odorant receptor co-receptor (Orco) is required. In this study, we deleted the Orco gene in the Lepidopteran model insect, Bombyx mori, using a binary transgene-based clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system. We initially generated somatic mutations in two targeted sites, from which we obtained homozygous mutants with deletion of a 866 base pair sequence. Because of the flight inability of B. mori, we developed a novel method to examine the adult mating behavior. Considering the specialization in larval feeding, we examined food selection behavior in Orco somatic mutants by the walking trail analysis of silkworm position over time. Single sensillum recordings indicated that the antenna of the homozygous mutant was unable to respond to either of the two sex pheromones, bombykol or bombykal. An adult mating behavior assay revealed that the Orco mutant displayed a significantly impaired mating selection behavior in response to natural pheromone released by a wild-type female moth as well as an 11:1 mixture of bombykol/bombykal. The mutants also exhibited a decreased response to bombykol and, similar to wild-type moths, they displayed no response to bombykal. A larval feeding behavior assay revealed that the Orco mutant displayed defective selection for mulberry leaves and different concentrations of the volatile compound cis-jasmone found in mulberry leaves. Deletion of BmOrco severely disrupts the olfactory system, suggesting that BmOrco is indispensable in the olfactory pathway. The approach used for generating somatic and homozygous mutations also highlights a novel method for mutagenesis. This study on BmOrco function provides insights into the insect olfactory system and also provides a paradigm for agroforestry pest control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Differential Contributions of Olfactory Receptor Neurons in a Drosophila Olfactory Circuit

    PubMed Central

    Newquist, Gunnar; Novenschi, Alexandra; Kohler, Donovan

    2016-01-01

    Abstract The ability of an animal to detect, discriminate, and respond to odors depends on the functions of its olfactory receptor neurons (ORNs). The extent to which each ORN, upon activation, contributes to chemotaxis is not well understood. We hypothesized that strong activation of each ORN elicits a different behavioral response in the Drosophila melanogaster larva by differentially affecting the composition of its navigational behavior. To test this hypothesis, we exposed Drosophila larvae to specific odorants to analyze the effect of individual ORN activity on chemotaxis. We used two different behavioral paradigms to analyze the chemotaxis response of larvae to odorants. When tested with five different odorants that elicit strong physiological responses from single ORNs, larval behavioral responses toward each odorant differed in the strength of attraction as well as in the composition of discrete navigational elements, such as runs and turns. Further, behavioral responses to odorants did not correlate with either the strength of odor gradients tested or the sensitivity of each ORN to its cognate odorant. Finally, we provide evidence that wild-type larvae with all ORNs intact exhibit higher behavioral variance than mutant larvae that have only a single pair of functional ORNs. We conclude that individual ORNs contribute differently to the olfactory circuit that instructs chemotactic responses. Our results, along with recent studies from other groups, suggest that ORNs are functionally nonequivalent units. These results have implications for understanding peripheral odor coding. PMID:27570823

  6. Mechanisms underlying odorant-induced and spontaneous calcium signals in olfactory receptor neurons of spiny lobsters, Panulirus argus.

    PubMed

    Tadesse, Tizeta; Derby, Charles D; Schmidt, Manfred

    2014-01-01

    We determined if a newly developed antennule slice preparation allows studying chemosensory properties of spiny lobster olfactory receptor neurons under in situ conditions with Ca(2+) imaging. We show that chemical stimuli reach the dendrites of olfactory receptor neurons but not their somata, and that odorant-induced Ca(2+) signals in the somata are sufficiently stable over time to allow stimulation with a substantial number of odorants. Pharmacological manipulations served to elucidate the source of odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons. Both Ca(2+) signals are primarily mediated by an influx of extracellular Ca(2+) through voltage-activated Ca(2+) channels that can be blocked by CoCl2 and the L-type Ca(2+) channel blocker verapamil. Intracellular Ca(2+) stores contribute little to odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations. The odorant-induced Ca(2+) transients as well as the spontaneous Ca(2+) oscillations depend on action potentials mediated by Na(+) channels that are largely TTX-insensitive but blocked by the local anesthetics tetracaine and lidocaine. Collectively, these results corroborate the conclusion that odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons closely reflect action potential activity associated with odorant-induced phasic-tonic responses and spontaneous bursting, respectively. Therefore, both types of Ca(2+) signals represent experimentally accessible proxies of spiking.

  7. The effect of non-diabetic chronic renal failure on olfactory function.

    PubMed

    Koseoglu, S; Derin, S; Huddam, B; Sahan, M

    2017-05-01

    In chronic renal failure (CRF), deterioration of glomerular filtration results in accumulation of metabolites in the body which affect all organs. This study was performed to investigate the olfactory functions, and determine if hemodialysis or peritoneal dialysis improves olfactory function in non-diabetic CRF patients. The olfactory functions were analyzed in CRF patients not on a dialysis program and had a creatinine level≥2mg/dL, in CRF patients on hemodialysis or peritoneal dialysis, and in healthy controls. Diabetic patients were excluded since diabetes alone is a cause of olfactory dysfunction. The study group consisted of a total of 107 individuals including 38CRF patients on a hemodialysis program, 15 CRF patients on peritoneal dialysis, 30 patients with a creatinine level ≥ 2mg/dL without any need for dialysis, and 24 healthy controls with normal renal functions. Olfactory functions were analyzed with "Sniffin' sticks" test, and the groups were compared for the test results. All test parameters were impaired in patients with CRF. The median TDI scores of the patients with CRF and the healthy subjects were 24.75 (13-36) and 32.5 (27.75-37.75), respectively, with a statistically significant difference in between (P<0.001). The olfactory functions for the dialysis patients were better than those for the CRF patients not on a dialysis program (P=0.020). Non-diabetic CRF affects olfactory functions negatively. Dialysis improves olfactory functions in those patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Non-conventional Frizzled ligands and Wnt receptors.

    PubMed

    Hendrickx, Marijke; Leyns, Luc

    2008-05-01

    The Wnt family of secreted signaling factors plays numerous roles in embryonic development and in stem cell biology. In the adult, Wnt signaling is involved in tissue homeostasis and mutations that lead to the overexpression of Wnt can be linked to cancer. Wnt signaling is transduced intracellularly by the Frizzled (Fzd) family of receptors. In the canonical pathway, accumulation of beta-catenin and the subsequent formation of a complex with T cell factors (TCF) or lymphoid enhancing factors (Lef) lead to target gene activation. The identification of Ryk as an alternative Wnt receptor and the discovery of the novel Fzd ligands Norrie disease protein (NDP) and R-Spondin, changed the traditional view of Wnts binding to Fzd receptors. Mouse R-Spondin cooperates with Wnt signaling and Low density lipoprotein (LDL) receptor related protein (LRP) to activate beta-catenin dependent gene expression and is involved in processes such as limb and placental development in the mouse. NDP is the product of the Norrie disease gene and controls vascular development in the retina, inner ear and in the female reproductive system during pregnancy. In this review a functional overview of the interactions of the different Wnt and non-Wnt ligands with the Fzd receptors is given as well as a survey of Wnts binding to Ryk and we discuss the biological significance of these interactions.

  9. Tonic and Phasic Receptor Neurons in the Vertebrate Olfactory Epithelium

    PubMed Central

    Madrid, Rodolfo; Sanhueza, Magdalena; Alvarez, Osvaldo; Bacigalupo, Juan

    2003-01-01

    Olfactory receptor neurons (ORNs) respond to odorants with characteristic patterns of action potentials that are relevant for odor coding. Prolonged odorant exposures revealed three populations of dissociated toad ORNs, which were mimicked by depolarizing currents: tonic (TN, displaying sustained firing, 49% of 102 cells), phasic (PN, exhibiting brief action potential trains, 36%) and intermediate neurons (IN, generating trains longer than PN, 15%). We studied the biophysical properties underlying the differences between TNs and PNs, the most extreme cases among ORNs. TNs and PNs possessed similar membrane capacitances (∼4 pF), but they differed in resting potential (−82 versus −64 mV), input resistance (4.2 versus 2.9 GΩ) and unspecific current, Iu (TNs: 0 < Iu ≤ 1 pA/pF; and PNs: Iu > 1 pA/pF). Firing behavior did not correlate with differences in voltage-gated conductances. We developed a mathematical model that accurately simulates tonic and phasic patterns. Whole cell recordings from rat ORNs in fragments (∼4 mm2) of olfactory epithelium showed that such a tissue normally contains tonic and phasic receptor neurons, suggesting that this feature is common across a wide range of vertebrates. Our findings show that the individual passive electrical properties can govern the firing patterns of ORNs. PMID:12770919

  10. The physiological basics of the olfactory neuro-epithelium.

    PubMed

    Watelet, J B; Katotomichelakis, M; Eloy, P; Danielidis, V

    2009-01-01

    All living organisms can detect and identify chemical substances in their environment. The olfactory epithelium is covered by a mucus layer which is essential for the function of the olfactory neurons that are directly connected to the brain through the cribriform plate. However, little is known about the composition of this mucus in humans and its significance for the diagnosis of olfactory disorders. The olfactory epithelium consists of four primary cell types, including the olfactory receptor cells essential for odour transduction. This review examines the anatomical, histological and physiological fundamentals of olfactory mucosa. Particular attention is paid to the biochemical environment of the olfactory mucosa that regulates both peri-receptor events and several protective functions.

  11. Access to the odor world: olfactory receptors and their role for signal transduction in insects.

    PubMed

    Fleischer, Joerg; Pregitzer, Pablo; Breer, Heinz; Krieger, Jürgen

    2018-02-01

    The sense of smell enables insects to recognize and discriminate a broad range of volatile chemicals in their environment originating from prey, host plants and conspecifics. These olfactory cues are received by olfactory sensory neurons (OSNs) that relay information about food sources, oviposition sites and mates to the brain and thus elicit distinct odor-evoked behaviors. Research over the last decades has greatly advanced our knowledge concerning the molecular basis underlying the reception of odorous compounds and the mechanisms of signal transduction in OSNs. The emerging picture clearly indicates that OSNs of insects recognize odorants and pheromones by means of ligand-binding membrane proteins encoded by large and diverse families of receptor genes. In contrast, the mechanisms of the chemo-electrical transduction process are not fully understood; the present status suggests a contribution of ionotropic as well as metabotropic mechanisms. In this review, we will summarize current knowledge on the peripheral mechanisms of odor sensing in insects focusing on olfactory receptors and their specific role in the recognition and transduction of odorant and pheromone signals by OSNs.

  12. Dialing Up an Embryo: Are Olfactory Receptors Digits in a Developmental Code?

    ERIC Educational Resources Information Center

    Travis, John

    1998-01-01

    Scientist William J. Dreyer has hypothesized that the cell surface proteins in the nose that detect odors also help assemble embryos. These olfactory receptors and related proteins act as identifiers, much like the last few digits of a telephone number, that help cells to find their intended neighbors in a developing embryo. Discusses the research…

  13. In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles.

    PubMed

    Assié, Marie-Bernadette; Dominguez, Hélène; Consul-Denjean, Nathalie; Newman-Tancredi, Adrian

    2006-09-01

    Interaction with dopamine D2-like receptors plays a major role in the therapeutic effects of antipsychotic drugs. We examined in vivo dopamine D2 receptor occupancy of various established and potential antipsychotics in mouse striatum and olfactory tubercles 1 h after administration of the compound, using [3H]nemonapride as a ligand. All the compounds reduced in vivo binding of [3H]nemonapride in the striatum. When administered systemically, conventional antipsychotics, D2 antagonists, nemonapride (ID50: 0.034 mg/kg), eticlopride (0.047), haloperidol (0.11) and raclopride (0.11) potently inhibited [3H]nemonapride binding. The 'atypical' antipsychotics, risperidone (0.18), ziprasidone (0.38), aripiprazole (1.6), olanzapine (0.99), and clozapine (11.1) were less potent for occupying D2-like receptors. New compounds, displaying marked agonism at 5-HT1A receptors in addition to D2 receptor affinity, exhibited varying D2 receptor occupancy: bifeprunox (0.25), SLV313 (0.78), SSR181507 (1.6) and sarizotan (6.7). ID50 values for inhibition of [3H]nemonapride binding in the striatum correlated with those in the olfactory tubercles (r=0.95, P<0.0001). These values also correlated with previously-reported in vitro affinity of the compounds at rat D2 receptors (r=0.85, P=0.0001) and with inhibition of apomorphine-induced climbing in mice (r=0.79 P=0.0005). In contrast, there was no significant correlation between ID50 values herein and previously-reported ED50 values for catalepsy in mice. These data indicate that: (1) there is no difference in D2 receptor occupancy in limbic versus striatal regions between most classical and atypical or potential antipsychotics; and (2) high occupancy of D2 receptors can be dissociated from catalepsy, if the drugs also activate 5-HT1A receptors. Taken together, these data support the strategy of simultaneously targeting D2 receptor blockade and 5-HT1A receptor activation for new antipsychotics.

  14. Southern pine beetle: Olfactory receptor and behavior discrimination of enantiomers of the attractant pheromone frontalin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Payne, T.L.; Berisford, C.W.; Blum, M.S.

    1982-05-01

    In a laboratory and field bioassays, the response of Dendroctonus frontalis was significantly greater to the mixture of (1S,55R)-(-)-frontalin and alpha-pinene than to (1R,5S)-(+)-frontalin and alpha-pinene. Electrophysiologrical studies revealed that antennal olfactory receptor cells were significantly more responsive to (1S,5R)-(-)-frontalin than to 1R,5S)-(+) -frontalin. Both enanitiomers stimulated the same olfactory cells which suggests that each cell possesses at least two types of enanitomer-specific acceptors.

  15. Cellular organisation and functions of the olfactory epithelium of pearl spot Etroplus suratensis (Bloch): a light and scanning electron microscopic study.

    PubMed

    Ghosh, S K; Chakrabarti, P

    2010-08-01

    The cellular organisation of the olfactory rosettes of Etroplus suratensis was studied by light and scanning electron microscopy. The oval shaped olfactory rosette of the fish consists of 12 lamellae radiating from a central raphe. The olfactory lamellae are comprised of restricted areas of sensory epithelium and broad areas of non-sensory epithelium in the apical, middle, and basal regions. The sensory epithelium contains three types of receptor cells: microvillus, ciliated, and rod cells, as well as labyrinth cells and supporting cells. The non-sensory epithelium consists of stratified epithelial and mucous cells. The transitional region between the sensory and non-sensory epithelium consists of ciliated receptor cells, mucous cells, and stratified epithelial cells. The different cells on the olfactory epithelium were discussed regarding the functional significance of the fish concerned.

  16. Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

    NASA Technical Reports Server (NTRS)

    Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

    1996-01-01

    Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

  17. Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

    PubMed

    Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

    2016-01-01

    Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Expression of Olfactory Signaling Genes in the Eye

    PubMed Central

    Velmeshev, Dmitry; Faghihi, Mohammad; Shestopalov, Valery I.; Slepak, Vladlen Z.

    2014-01-01

    Purpose To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors. Methods Total RNA from the mouse cornea was subjected to next-generation sequencing using the Illumina platform. The data was analyzed with TopHat and CuffLinks software packages. Expression of a representative group of genes detected by RNA-seq was further analyzed by RT-PCR and in situ hybridization using RNAscope technology and fluorescent microscopy. Results We generated more than 46 million pair-end reads from mouse corneal RNA. Bioinformatics analysis revealed that the mouse corneal transcriptome reconstructed from these reads represents over 10,000 gene transcripts. We identified 194 GPCR transcripts, of which 96 were putative olfactory receptors. RT-PCR analysis confirmed the presence of several olfactory receptors and related genes, including olfactory marker protein and the G protein associated with olfaction, Gαolf. In situ hybridization showed that mRNA for olfactory marker protein, Gαolf and possibly some olfactory receptors were found in the corneal epithelial cells. In addition to the corneal epithelium, Gαolf was present in the ganglionic and inner nuclear layers of the retina. One of the olfactory receptors, Olfr558, was present primarily in vessels of the eye co-stained with antibodies against alpha-smooth muscle actin, indicating expression in arterioles. Conclusions Several species of mRNA encoding putative olfactory receptors and related genes are expressed in the mouse cornea and other parts of the eye indicating they may play a role in sensing chemicals in the ocular environment. PMID:24789354

  19. [Organization of olfactory system of the Indian major carp Labeo rohita (Ham.): a study using scanning and transmission microscopy].

    PubMed

    Bhute, Y V; Baile, V V

    2007-01-01

    Catla catla, Labeo rohita, and Cirrhinus mrigala are important alimentary fish in India. Their reproduction (breeding) depends on season. The fish perceive external factors-stimuli and chemical signals through the olfactory system that plays the key role in the central regulation of reproduction. However, in the available literature, any electron microscopy data on organization of olfactory elements in these fish are absent. We have studied ultrastructure of the olfactory organ in male L. rohita by using scanning (SEM) and transmission electron microscopy (TEM). The olfactory organ consists of olfactory epithelium, a short nerve, and olfactory bulb. The organ has oval shape and consists of approximately 47-52 lamellae in adult fish and of 14-20 lamellae in fish at the stage of fingerling. These lamellae originate from the midline raphe. By using SEM, the presence of microvillar sensory and ciliated non-sensory cells in these lamellae is shown. By using TEM, a microvillar receptor cell is revealed, which has rough endoplasmic reticulum and Golgi apparatus towards the apical end. Basal cells are found at the base of the receptor cell; supporting cells are located adjacent to olfactory receptor neurons, while epithelial cells--in the non-sensory part of olfactory epithelium. Mast, blastema and macrophages cells are also found in the basal lamina. This work is the first publication on structural organization of olfactory system of the Indian major carp, which provides information about morphological and ultrastructural organization of olfactory system and opens new opportunities for study of chemical neuroanatomy, sensory signal processing, and nervous regulation of reproduction of the Indian major carp.

  20. Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.

    PubMed

    Ferreira, A; Dahlöf, L G; Hansen, S

    1987-10-01

    During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system and the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experiments, to play a crucial role in maternal aggression.

  1. Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity.

    PubMed

    Ferguson, Christopher H; Zhao, Haiqing

    2017-01-04

    In vertebrate olfactory sensory neurons (OSNs), Ca 2+ plays key roles in both mediating and regulating the olfactory response. Ca 2+ enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca 2+ -activated chloride channel to amplify the response. Ca 2+ also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca 2+ /calmodulin (CaM), to reduce the response. Ca 2+ is removed from the cilia primarily by the K + -dependent Na + /Ca 2+ exchanger 4 (NCKX4), and the removal of Ca 2+ leads to closure of the chloride channel and response termination. In this study, we investigate how two mechanisms conventionally considered negative regulatory mechanisms of olfactory transduction, Ca 2+ removal by NCKX4, and desensitization of the CNG channel by Ca 2+ /CaM, interact to regulate the olfactory response. We performed electro-olfactogram (EOG) recordings on the double-mutant mice, NCKX4 -/- ;CNGB1 ΔCaM , which are simultaneously lacking NCKX4 (NCKX4 -/- ) and Ca 2+ /CaM-mediated CNG channel desensitization (CNGB1 ΔCaM ). Despite exhibiting alterations in various response attributes, including termination kinetics and adaption properties, OSNs in either NCKX4 -/- mice or CNGB1 ΔCaM mice show normal resting sensitivity, as determined by their unchanged EOG response amplitude. We found that OSNs in NCKX4 -/- ;CNGB1 ΔCaM mice displayed markedly reduced EOG amplitude accompanied by alterations in other response attributes. This study suggests that what are conventionally considered negative regulatory mechanisms of olfactory transduction also play a role in setting the resting sensitivity in OSNs. Sensory receptor cells maintain high sensitivity at rest. Although the mechanisms responsible for setting the resting sensitivity of sensory receptor cells are not

  2. Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

    PubMed

    Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

    2015-02-15

    Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p<0.001), albeit also better than patients with mild AD (p<.001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

  3. Olfactory transduction pathways in the Senegalese sole Solea senegalensis.

    PubMed

    Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M

    2013-09-01

    This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms. © 2013 The Fisheries Society of the British Isles.

  4. Individual olfactory perception reveals meaningful nonolfactory genetic information

    PubMed Central

    Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam

    2015-01-01

    Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information. PMID:26100865

  5. Cooperative interactions enable singular olfactory receptor expression in mouse olfactory neurons

    PubMed Central

    Monahan, Kevin; Schieren, Ira; Cheung, Jonah; Mumbey-Wafula, Alice; Monuki, Edwin S

    2017-01-01

    The monogenic and monoallelic expression of only one out of >1000 mouse olfactory receptor (ORs) genes requires the formation of large heterochromatic chromatin domains that sequester the OR gene clusters. Within these domains, intergenic transcriptional enhancers evade heterochromatic silencing and converge into interchromosomal hubs that assemble over the transcriptionally active OR. The significance of this nuclear organization in OR choice remains elusive. Here, we show that transcription factors Lhx2 and Ebf specify OR enhancers by binding in a functionally cooperative fashion to stereotypically spaced motifs that defy heterochromatin. Specific displacement of Lhx2 and Ebf from OR enhancers resulted in pervasive, long-range, and trans downregulation of OR transcription, whereas pre-assembly of a multi-enhancer hub increased the frequency of OR choice in cis. Our data provide genetic support for the requirement and sufficiency of interchromosomal interactions in singular OR choice and generate general regulatory principles for stochastic, mutually exclusive gene expression programs. PMID:28933695

  6. A Cleavable N-Terminal Signal Peptide Promotes Widespread Olfactory Receptor Surface Expression in HEK293T Cells

    PubMed Central

    Shepard, Blythe D.; Natarajan, Niranjana; Protzko, Ryan J.; Acres, Omar W.; Pluznick, Jennifer L.

    2013-01-01

    Olfactory receptors (ORs) are G protein-coupled receptors that detect odorants in the olfactory epithelium, and comprise the largest gene family in the genome. Identification of OR ligands typically requires OR surface expression in heterologous cells; however, ORs rarely traffic to the cell surface when exogenously expressed. Therefore, most ORs are orphan receptors with no known ligands. To date, studies have utilized non-cleavable rhodopsin (Rho) tags and/or chaperones (i.e. Receptor Transporting Protein, RTP1S, Ric8b and Gαolf) to improve surface expression. However, even with these tools, many ORs still fail to reach the cell surface. We used a test set of fifteen ORs to examine the effect of a cleavable leucine-rich signal peptide sequence (Lucy tag) on OR surface expression in HEK293T cells. We report here that the addition of the Lucy tag to the N-terminus increases the number of ORs reaching the cell surface to 7 of the 15 ORs (as compared to 3/15 without Rho or Lucy tags). Moreover, when ORs tagged with both Lucy and Rho were co-expressed with previously reported chaperones (RTP1S, Ric8b and Gαolf), we observed surface expression for all 15 receptors examined. In fact, two-thirds of Lucy-tagged ORs are able to reach the cell surface synergistically with chaperones even when the Rho tag is removed (10/15 ORs), allowing for the potential assessment of OR function with only an 8-amino acid Flag tag on the mature protein. As expected for a signal peptide, the Lucy tag was cleaved from the mature protein and did not alter OR-ligand binding and signaling. Our studies demonstrate that widespread surface expression of ORs can be achieved in HEK293T cells, providing promise for future large-scale deorphanization studies. PMID:23840901

  7. Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

    PubMed

    Strowbridge, Ben W

    2010-02-11

    In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Possible roles for products of polymorphic MHC and linked olfactory receptor genes during selection processes in reproduction.

    PubMed

    Ziegler, Andreas; Dohr, Gotrfried; Uchanska-Ziegler, Barbara

    2002-07-01

    Polymorphic genes of the human major histocompatibility complex [MHC; human leukocyte antigen (HLA)] are probably important in determining resistance to parasites and avoidance of inbreeding. We investigated whether HLA-associated sexual selection could also involve HLA-linked olfactory receptor (OR) genes, which might not only participate in olfaction-guided mate choice, but also in selection processes within the testis. The testicular expression status of HLA class I molecules (by immunohistology) and HLA-linked OR genes (by transcriptional analysis) was determined. Various HLA class I heavy chains, but not beta2-microglobulin (beta2m), were expressed, mainly at the spermatocyte I stage. Of 17 HLA-linked OR genes analyzed, eight were found to be transcribed in the testis. They exhibited varying numbers of 5'- or 3'-non-coding exons as well as differential splicing. We suggest that testis-expressed polymorphic HLA and OR proteins are functionally connected and serve the selection of spermatozoa, enabling them to distinguish 'self from 'non-self [the sperm-receptor-selection (SRS) hypothesis].

  9. Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival

    PubMed Central

    François, Adrien; Laziz, Iman; Rimbaud, Stéphanie; Grebert, Denise; Durieux, Didier; Pajot-Augy, Edith; Meunier, Nicolas

    2013-01-01

    The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants. PMID:24399931

  10. MiR-132 regulated olfactory bulb proteins linked to olfactory learning in greater short-nosed fruit bat Cynopterus sphinx.

    PubMed

    Mukilan, Murugan; Rajathei, David Mary; Jeyaraj, Edwin; Kayalvizhi, Nagarajan; Rajan, Koilmani Emmanuvel

    2018-05-30

    Earlier, we showed that micro RNA-132 (miR-132) regulate the immediate early genes (IEGs) in the olfactory bulb (OB) of fruit bat Cynopterus sphinx during olfactory learning. This study was designed to examine whether the miR-132 regulate other proteins in OB during olfactory learning. To test this, miR-132 anti-sense oligodeoxynucleotide (AS-ODN) was delivered to the OB and then trained to novel odor. The 2-dimensional gel electrophoresis analysis showed that inhibition of miR-132 altered olfactory training induced expression of 321 proteins. Further, liquid chromatography-mass spectrometry (LC-MS/MS) analysis reveals the identity of differently expressed proteins such as phosphoribosyl transferase domain containing protein (PRTFDC 1), Sorting nexin-8 (SNX8), Creatine kinase B-type (CKB) and Annexin A11 (ANX A11). Among them PRTFDC 1 showing 189 matching peptides with highest sequence coverage (67.0%) and protein-protein interaction analysis showed that PRTFDC 1 is a homolog of hypoxanthine phosphoribosyltransferase-1 (HPRT-1). Subsequent immunohistochemical analysis (IHC) showed that inhibition of miR-132 down-regulated HPRT expression in OB of C. sphinx. In addition, western blot analysis depicts that HPRT, serotonin transporter (SERT), N-methyl-d-asparate (NMDA) receptors (2A,B) were down-regulated, but not altered in OB of non-sense oligodeoxynucleotide (NS-ODN) infused groups. These analyses suggest that miR-132 regulates the process of olfactory learning and memory formation through SERT and NMDA receptors signalling, which is possibly associated with the PRTFDC1-HPRT interaction. Copyright © 2017. Published by Elsevier B.V.

  11. Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans

    PubMed Central

    Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O.

    2018-01-01

    In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants (n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort. PMID:29740266

  12. Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans.

    PubMed

    Maharjan, Ashim; Wang, Eunice; Peng, Mei; Cakmak, Yusuf O

    2018-01-01

    In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants ( n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT ( p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS ( p = 0.014, post-hoc with Bonferroni correction ) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

  13. Cyclic-nucleotide–gated cation current and Ca2+-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

    PubMed Central

    Li, Rong-Chang; Ben-Chaim, Yair; Yau, King-Wai; Lin, Chih-Chun

    2016-01-01

    Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide–gated (CNG), nonselective cation channels. The consequent Ca2+ influx triggers adaptation but also signal amplification, the latter by opening a Ca2+-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose–response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca2+-activated Cl current does not influence the behavioral olfactory threshold in mice. PMID:27647918

  14. Olfactory receptor neurons use gain control and complementary kinetics to encode intermittent odorant stimuli

    PubMed Central

    Gorur-Shandilya, Srinivas; Demir, Mahmut; Long, Junjiajia; Clark, Damon A; Emonet, Thierry

    2017-01-01

    Insects find food and mates by navigating odorant plumes that can be highly intermittent, with intensities and durations that vary rapidly over orders of magnitude. Much is known about olfactory responses to pulses and steps, but it remains unclear how olfactory receptor neurons (ORNs) detect the intensity and timing of natural stimuli, where the absence of scale in the signal makes detection a formidable olfactory task. By stimulating Drosophila ORNs in vivo with naturalistic and Gaussian stimuli, we show that ORNs adapt to stimulus mean and variance, and that adaptation and saturation contribute to naturalistic sensing. Mean-dependent gain control followed the Weber-Fechner relation and occurred primarily at odor transduction, while variance-dependent gain control occurred at both transduction and spiking. Transduction and spike generation possessed complementary kinetic properties, that together preserved the timing of odorant encounters in ORN spiking, regardless of intensity. Such scale-invariance could be critical during odor plume navigation. DOI: http://dx.doi.org/10.7554/eLife.27670.001 PMID:28653907

  15. The stimulatory Gα(s) protein is involved in olfactory signal transduction in Drosophila.

    PubMed

    Deng, Ying; Zhang, Weiyi; Farhat, Katja; Oberland, Sonja; Gisselmann, Günter; Neuhaus, Eva M

    2011-04-07

    Seven-transmembrane receptors typically mediate olfactory signal transduction by coupling to G-proteins. Although insect odorant receptors have seven transmembrane domains like G-protein coupled receptors, they have an inverted membrane topology, constituting a key difference between the olfactory systems of insects and other animals. While heteromeric insect ORs form ligand-activated non-selective cation channels in recombinant expression systems, the evidence for an involvement of cyclic nucleotides and G-proteins in odor reception is inconsistent. We addressed this question in vivo by analyzing the role of G-proteins in olfactory signaling using electrophysiological recordings. We found that Gα(s) plays a crucial role for odorant induced signal transduction in OR83b expressing olfactory sensory neurons, but not in neurons expressing CO₂ responsive proteins GR21a/GR63a. Moreover, signaling of Drosophila ORs involved Gα(s) also in a heterologous expression system. In agreement with these observations was the finding that elevated levels of cAMP result in increased firing rates, demonstrating the existence of a cAMP dependent excitatory signaling pathway in the sensory neurons. Together, we provide evidence that Gα(s) plays a role in the OR mediated signaling cascade in Drosophila.

  16. Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

    PubMed

    Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

    2015-09-11

    Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

  17. Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding

    PubMed Central

    Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

    2015-01-01

    Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (−)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite “supersensitivity” to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 108-fold differential sensitivity of ΔD mice to (−)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >1010-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (−)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This “enantiomer odour discrimination paradox” indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification. PMID:26361056

  18. Ancient genomic architecture for mammalian olfactory receptor clusters

    PubMed Central

    Aloni, Ronny; Olender, Tsviya; Lancet, Doron

    2006-01-01

    Background Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome. Results We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection. Conclusion The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence. PMID:17010214

  19. Parallel processing of afferent olfactory sensory information

    PubMed Central

    Vaaga, Christopher E.

    2016-01-01

    Key points The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood.One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation.Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons.Compared to external tufted cells, mitral cells have a prolonged afferent‐evoked EPSC, which serves to amplify the synaptic input.The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells.Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. Abstract Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1‐fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5‐fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic

  20. Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

    PubMed

    Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

    2013-09-03

    Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

  1. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: A patch clamp analysis in gene-targeted mice

    PubMed Central

    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M.; Ma, Minghong

    2006-01-01

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli. PMID:16446455

  2. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice.

    PubMed

    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M; Ma, Minghong

    2006-02-07

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli.

  3. Transduction in Drosophila olfactory receptor neurons is invariant to air speed

    PubMed Central

    Zhou, Yi

    2012-01-01

    In the vertebrate nose, increasing air speed tends to increase the magnitude of odor-evoked activity in olfactory receptor neurons (ORNs), given constant odor concentration and duration. It is often assumed that the same is true of insect olfactory organs, but this has not been directly tested. In this study, we examined the effect of air speed on ORN responses in Drosophila melanogaster. We constructed an odor delivery device that allowed us to independently vary concentration and air speed, and we used a fast photoionization detector to precisely measure the actual odor concentration at the antenna while simultaneously recording spikes from ORNs in vivo. Our results demonstrate that Drosophila ORN odor responses are invariant to air speed, as long as odor concentration is kept constant. This finding was true across a >100-fold range of air speeds. Because odor hydrophobicity has been proposed to affect the air speed dependence of olfactory transduction, we tested a >1,000-fold range of hydrophobicity values and found that ORN responses are invariant to air speed across this full range. These results have implications for the mechanisms of odor delivery to Drosophila ORNs. Our findings are also significant because flies have a limited ability to control air flow across their antennae, unlike terrestrial vertebrates, which can control air flow within their nasal cavity. Thus, for the fly, invariance to air speed may be adaptive because it confers robustness to changing wind conditions. PMID:22815404

  4. Morphology of the olfactory system in the predatory mite Phytoseiulus persimilis.

    PubMed

    van Wijk, Michiel; Wadman, Wytse J; Sabelis, Maurice W

    2006-01-01

    The predatory mite Phytoseiulus persimilis locates its prey, the two-spotted spider mite, by means of herbivore-induced plant volatiles. The olfactory response to this quantitatively and qualitatively variable source of information is particularly well documented. The mites perform this task with a peripheral olfactory system that consists of just five putative olfactory sensilla that reside in a dorsal field at the tip of their first pair of legs. The receptor cells innervate a glomerular olfactory lobe just ventral of the first pedal ganglion. We have made a 3D reconstruction of the caudal half of the olfactory lobe in adult females. The glomerular organization as well as the glomerular innervation appears conserved across different individuals. The adult females have, by approximation, a 1:1 ratio of olfactory receptor cells to olfactory glomeruli.

  5. Expression of corticosteroid binding globulin in the rat olfactory system.

    PubMed

    Dölz, Wilfried; Eitner, Annett; Caldwell, Jack D; Jirikowski, Gustav F

    2013-05-01

    Glucocorticoids are known to act on the olfactory system although their mode of action is still unclear since nuclear glucocorticoid receptors are mostly absent in the olfactory mucosa. In this study we used immunocytochemistry, in situ hybridization, and RT-PCR to study the expression and distribution of corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet cells could be immunostained for CBG. Nasal secretion contained measurable amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was localized in many of the basal cells of the olfactory mucosa, while mature sensory cells contained CBG only in processes as determined by double immunostaining with the olfactory marker protein OMP. This staining was most pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non-sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb indicated axonal transport. Portions of the periglomerular cells, the mitral cells and the tufted cells were also CBG positive. CBG encoding transcripts were confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG may be significant for uptake, accumulation and transport of glucocorticoids, including aerosolic cortisol. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Perforated Patch-clamp Recording of Mouse Olfactory Sensory Neurons in Intact Neuroepithelium: Functional Analysis of Neurons Expressing an Identified Odorant Receptor

    PubMed Central

    Jarriault, David; Grosmaitre, Xavier

    2015-01-01

    Analyzing the physiological responses of olfactory sensory neurons (OSN) when stimulated with specific ligands is critical to understand the basis of olfactory-driven behaviors and their modulation. These coding properties depend heavily on the initial interaction between odor molecules and the olfactory receptor (OR) expressed in the OSNs. The identity, specificity and ligand spectrum of the expressed OR are critical. The probability to find the ligand of the OR expressed in an OSN chosen randomly within the epithelium is very low. To address this challenge, this protocol uses genetically tagged mice expressing the fluorescent protein GFP under the control of the promoter of defined ORs. OSNs are located in a tight and organized epithelium lining the nasal cavity, with neighboring cells influencing their maturation and function. Here we describe a method to isolate an intact olfactory epithelium and record through patch-clamp recordings the properties of OSNs expressing defined odorant receptors. The protocol allows one to characterize OSN membrane properties while keeping the influence of the neighboring tissue. Analysis of patch-clamp results yields a precise quantification of ligand/OR interactions, transduction pathways and pharmacology, OSNs' coding properties and their modulation at the membrane level.  PMID:26275097

  7. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    PubMed

    Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

    2016-01-01

    limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

  8. Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates

    PubMed Central

    Wiebe, Victor; Przeworski, Molly; Lancet, Doron; Pääbo, Svante

    2004-01-01

    Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates. PMID:14737185

  9. Baicalin Modulates APPL2/Glucocorticoid Receptor Signaling Cascade, Promotes Neurogenesis, and Attenuates Emotional and Olfactory Dysfunctions in Chronic Corticosterone-Induced Depression.

    PubMed

    Gao, Chong; Du, Qiaohui; Li, Wenting; Deng, Ruixia; Wang, Qi; Xu, Aimin; Shen, Jiangang

    2018-04-19

    Olfactory dysfunction is often accompanied with anxiety- and depressive-like behaviors in depressive patients. Impaired neurogenesis in hippocampus and subventricular zone (SVZ)-olfactory bulb (OB) contribute to anxiety- and depressive-like behaviors and olfactory dysfunctions. However, the underlying mechanisms of olfactory dysfunction remain unclear. Our previous study indicates that adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2), could affect the activity and sensitivity of glucocorticoid receptor (GR) and mediate impaired hippocampal neurogenesis, which contribute the development of depression. In the present study, we further identified the roles of APPL2 in olfactory functions. APPL2 Tg mice displayed higher GR activity and less capacity of neurogenesis at olfactory system with less olfactory sensitivity than WT mice, indicating that APPL2 could be a potential therapeutic target for depression and olfactory deficits. We then studied the effects of baicalin, a medicinal herbal compound, on modulating APPL2/GR signaling pathway for promoting neurogenesis and antidepressant as well as improving olfactory functions. Baicalin treatment inhibited APPL2/GR signaling pathway and improved neurogenesis at SVZ, OB, and hippocampus in APPL2 Tg mice and chronic corticosterone-induced depression mouse model. Behavioral tests revealed that baicalin attenuated depressive- and anxiety-like behaviors and improve olfactory functions in the chronic depression mouse model and APPL2 Tg mice. Taken together, APPL2 could be a novel therapeutic target for improving depressant-related olfactory dysfunctions and baicalin could inhibit APPL2-mediated GR hyperactivity and promote adult neurogenesis, subsequently releasing depressive and anxiety symptoms and improving olfactory functions for antidepressant therapy.

  10. Electro-olfactogram and multiunit olfactory receptor responses to binary and trinary mixtures of amino acids in the channel catfish, Ictalurus punctatus

    PubMed Central

    1989-01-01

    In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type. PMID:2703818

  11. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

    PubMed

    Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

    2018-01-01

    Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  12. Attractiveness of fruit and flower odorants detected by olfactory receptor neurons in the fruit chafer Pachnoda marginata.

    PubMed

    Larsson, Mattias C; Stensmyr, Marcus C; Bice, Shannon B; Hansson, Bill S

    2003-05-01

    We studied the attraction of the African fruit chafer Pachnoda marginata Drury (Coleoptera: Scarabaeidae) to banana and 34 synthetic plant compounds previously shown to be detected by P. marginata olfactory receptor neurons. The behavioral studies were carried out in a two-choice olfactometer, where the attraction of beetles to lures and controls was monitored in 30-min intervals during whole days. Monitoring of the attraction over time gave additional information when comparing relative attractiveness of different compounds. Seventeen of the test compounds, primarily phenylic compounds, fruit esters, isovaleric acid, acetoin, and some floral or fruit terpenes, were attractive to P. marginata. Compounds showing no attractiveness included green leaf volatiles, lactones. and several alcohols, but also phenylic compounds and esters. One case of blend synergism was demonstrated, as well as some examples of sexual dimorphism in attraction. The significance of certain compounds and receptor neurons for olfactory-guided behavior of phytophagous scarabs is discussed.

  13. Annual life-history dependent seasonal differences in neural activity of the olfactory system between non-migratory and migratory songbirds.

    PubMed

    Rastogi, Ashutosh; Surbhi; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

    2016-01-01

    Present study investigated seasonal plasticity in neural activity of the olfactory system, and assessed whether this was influenced by differences in seasonal life-history states (LHSs) between the non-migratory and migratory birds. Brains of non-migratory Indian weaver birds and migratory redheaded buntings were processed for ZENK immunohistochemistry, a marker of neuronal activation, at the times of equinoxes (March, September) and solstices (June, December), which correspond with the periods of different seasonal LHSs during the year. Immunoreactivity was quantified in brain regions comprising the olfactory system viz. olfactory bulb (OB), anterior olfactory nucleus (AON), prepiriform cortex (CPP), lateral olfactory tract (LOT) and olfactory cortex (piriform cortex, CPI; lateral olfactory cortex, LOC). In weaver birds, ZENK-like immunoreactive (ZENK-lir) cells were significantly higher in all the brain areas during post-breeding season (September) than during the other seasons; OBs had higher neuronal activity in the breeding season (June), however. A similar neural activity pattern but at enhanced levels was found in migratory buntings almost all the year. These results for the first time show LHS-associated differences in the seasonal plasticity of a sensory system between the non-migratory and migratory songbirds. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Comprehensive Analysis of Non-Synonymous Natural Variants of G Protein-Coupled Receptors.

    PubMed

    Kim, Hee Ryung; Duc, Nguyen Minh; Chung, Ka Young

    2018-03-01

    G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as β-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.

  15. Association between olfactory identification and parkinsonism in patients with non-affective psychosis.

    PubMed

    Meijer, Julia H; van Harten, Peter; Meijer, Carin J; Koeter, Maarten W; Bruggeman, Richard; Cahn, Wiepke; Kahn, René S; de Haan, L

    2016-10-01

    Olfactory identification deficits (OIDs) are seen in schizophrenia patients and individuals at increased risk for psychosis but its pathophysiology remains unclear. Although dopaminergic imbalance is known to lie at the core of schizophrenia symptomatology, its role in the development of OIDs has not been elucidated yet. This study investigated the association between OIDs and symptoms of parkinsonism as a derivative of dopaminergic functioning. In 320 patients diagnosed with non-affective psychosis, olfactory identification performance was assessed by means of the Sniffin' Sticks task. Level of parkinsonian symptoms was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III). By means of multiple linear regression with bootstrapping, the association between UPDRS and Sniffin' Sticks score was investigated while correcting for potential confounders. A Bonferroni corrected P-value of 0.007 was used. Higher UPDRS scores significantly predicted worse olfactory identification in patients with non-affective psychosis with an unadjusted b = -0.07 (95% CI -0.10 to -0.04) and an adjusted b = -0.04 (95% CI -0.07 to -0.01). Results provide preliminary evidence that the same vulnerability may underlie the development of parkinsonism and OIDs in patients with non-affective psychosis. Further investigation should evaluate the clinical value of OIDs as a marker of dopaminergic vulnerability that may predict psychosis. © 2014 Wiley Publishing Asia Pty Ltd.

  16. Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

    PubMed Central

    Lee, Anderson C.; Tian, Huikai; Grosmaitre, Xavier

    2009-01-01

    The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)—2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3–27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed. PMID:19759360

  17. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice.

    PubMed

    Lee, Anderson C; Tian, Huikai; Grosmaitre, Xavier; Ma, Minghong

    2009-10-01

    The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)-2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3-27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed.

  18. Existence of multiple receptors in single neurons: responses of single bullfrog olfactory neurons to many cAMP-dependent and independent odorants.

    PubMed

    Kashiwayanagi, M; Shimano, K; Kurihara, K

    1996-11-04

    The responses of single bullfrog olfactory neurons to various odorants were measured with the whole-cell patch clamp which offers direct information on cellular events and with the ciliary recording technique to obtain stable quantitative data from many neurons. A large portion of single olfactory neurons (about 64% and 79% in the whole-cell recording and in the ciliary recording, respectively) responded to many odorants with quite diverse molecular structures, including both odorants previously indicated to be cAMP-dependent (increasing) and independent odorants. One odorant elicited a response in many cells; e.g. hedione and citralva elicited the response in 100% and 92% of total neurons examined with the ciliary recording technique. To confirm that a single neuron carries different receptors or transduction pathways, the cross-adaptation technique was applied to single neurons. Application of hedione to a single neuron after desensitization of the current in response to lyral or citralva induced an inward current with a similar magnitude to that applied alone. It was suggested that most single olfactory neurons carry multiple receptors and at least dual transduction pathways.

  19. Dynamical Modeling of the Moth Pheromone-Sensitive Olfactory Receptor Neuron within Its Sensillar Environment

    PubMed Central

    Gu, Yuqiao; Rospars, Jean-Pierre

    2011-01-01

    In insects, olfactory receptor neurons (ORNs), surrounded with auxiliary cells and protected by a cuticular wall, form small discrete sensory organs – the sensilla. The moth pheromone-sensitive sensillum is a well studied example of hair-like sensillum that is favorable to both experimental and modeling investigations. The model presented takes into account both the molecular processes of ORNs, i.e. the biochemical reactions and ionic currents giving rise to the receptor potential, and the cellular organization and compartmentalization of the organ represented by an electrical circuit. The number of isopotential compartments needed to describe the long dendrite bearing pheromone receptors was determined. The transduction parameters that must be modified when the number of compartments is increased were identified. This model reproduces the amplitude and time course of the experimentally recorded receptor potential. A first complete version of the model was analyzed in response to pheromone pulses of various strengths. It provided a quantitative description of the spatial and temporal evolution of the pheromone-dependent conductances, currents and potentials along the outer dendrite and served to determine the contribution of the various steps in the cascade to its global sensitivity. A second simplified version of the model, utilizing a single depolarizing conductance and leak conductances for repolarizing the ORN, was derived from the first version. It served to analyze the effects on the sensory properties of varying the electrical parameters and the size of the main sensillum parts. The consequences of the results obtained on the still uncertain mechanisms of olfactory transduction in moth ORNs – involvement or not of G-proteins, role of chloride and potassium currents – are discussed as well as the optimality of the sensillum organization, the dependence of biochemical parameters on the neuron spatial extension and the respective contributions of the

  20. Insights into the olfactory system of the ectoparasite Caligus rogercresseyi: molecular characterization and gene transcription analysis of novel ionotropic receptors.

    PubMed

    Núñez-Acuña, Gustavo; Valenzuela-Muñoz, Valentina; Marambio, Jorge Pino; Wadsworth, Simon; Gallardo-Escárate, Cristian

    2014-10-01

    Although various elements of the olfactory system have been elucidated in insects, it remains practically unstudied in crustaceans at a molecular level. Among crustaceans, some species are classified as ectoparasites that impact the finfish aquaculture industry. Thus, there is an urgent need to identify and comprehend the signaling pathways used by these in host recognition. The present study, through RNA-seq and qPCR analyses, found novel transcripts involved in the olfactory system of Caligus rogercresseyi, in addition to the transcriptomic patterns expressed during different stages of salmon lice development. From a transcriptomic library generated by Illumina sequencing, contigs that annotated for ionotropic receptors and other genes implicated in the olfactory system were identified and extracted. Full length mRNA was obtained for the ionotropic glutamate receptor 25, which had 3923 bp, and for the glutamate receptor ionotropic kainate 2, which had 2737 bp. Furthermore, two other transcripts identified as glutamate receptor, ionotropic kainate 2-like were found. In silico analysis was performed for the transcription expression from different stages of development in C. rogercresseyi, and clusters according to RPKM values were constructed. Gene transcription data were validated through qPCR assays in ionotropic receptors, and showed an expression of glutamate receptor 25 associated with the copepodid stage whereas adults, especially male adults, were associated with the kainate 2 and kainate 2-like transcripts. Additionally, gene transcription analysis of the ionotropic receptors showed an overexpression in response to the presence of masking compounds and immunostimulant in salmon diets. This response correlated to a reduction in sea lice infection following in vivo challenge. Diets with masking compounds showed a decrease of lice infestation of up to 25%. This work contributes to the available knowledge on chemosensory systems in this ectoparasite, providing

  1. Topographic mapping--the olfactory system.

    PubMed

    Imai, Takeshi; Sakano, Hitoshi; Vosshall, Leslie B

    2010-08-01

    Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils--the olfactory glomeruli--that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.

  2. Roles of specific membrane lipid domains in EGF receptor activation and cell adhesion molecule stabilization in a developing olfactory system.

    PubMed

    Gibson, Nicholas J; Tolbert, Leslie P; Oland, Lynne A

    2009-09-29

    Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-beta-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons.

  3. Roles of Specific Membrane Lipid Domains in EGF Receptor Activation and Cell Adhesion Molecule Stabilization in a Developing Olfactory System

    PubMed Central

    Gibson, Nicholas J.; Tolbert, Leslie P.; Oland, Lynne A.

    2009-01-01

    Background Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. Methodology/Principal Findings We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-β-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. Conclusions/Significance We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons. PMID:19787046

  4. Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23.

    PubMed

    Lam, Rebecca S; Mombaerts, Peter

    2013-07-01

    The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Lateral presynaptic inhibition mediates gain control in an olfactory circuit.

    PubMed

    Olsen, Shawn R; Wilson, Rachel I

    2008-04-24

    Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.

  6. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  7. G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons

    PubMed Central

    Connelly, Timothy; Yu, Yiqun; Grosmaitre, Xavier; Wang, Jue; Santarelli, Lindsey C.; Savigner, Agnes; Qiao, Xin; Wang, Zhenshan; Storm, Daniel R.; Ma, Minghong

    2015-01-01

    Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR–G protein coupling eliminates mechanical responses. Curiously, OSNs expressing different OR types display significantly different responses to mechanical stimuli. Genetic swap of putatively mechanosensitive ORs abolishes or reduces mechanical responses of OSNs. Furthermore, ectopic expression of an OR restores mechanosensitivity in loss-of-function OSNs. Lastly, heterologous expression of an OR confers mechanosensitivity to its host cells. These results indicate that certain ORs are both necessary and sufficient to cause mechanical responses, revealing a previously unidentified mechanism for mechanotransduction. PMID:25550517

  8. Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal transduction.

    PubMed

    Jin, Hye Jun; Lee, Sang Hun; Kim, Tae Hyun; Park, Juhun; Song, Hyun Seok; Park, Tai Hyun; Hong, Seunghun

    2012-05-15

    We developed a nanovesicle-based bioelectronic nose (NBN) that could recognize a specific odorant and mimic the receptor-mediated signal transmission of human olfactory systems. To build an NBN, we combined a single-walled carbon nanotube-based field effect transistor with cell-derived nanovesicles containing human olfactory receptors and calcium ion signal pathways. Importantly, the NBN took advantages of cell signal pathways for sensing signal amplification, enabling ≈ 100 times better sensitivity than that of previous bioelectronic noses based on only olfactory receptor protein and carbon nanotube transistors. The NBN sensors exhibited a human-like selectivity with single-carbon-atomic resolution and a high sensitivity of 1 fM detection limit. Moreover, this sensor platform could mimic a receptor-meditated cellular signal transmission in live cells. This sensor platform can be utilized for the study of molecular recognition and biological processes occurring at cell membranes and also for various practical applications such as food screening and medical diagnostics. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Modification of Male Courtship Motivation by Olfactory Habituation via the GABAA Receptor in Drosophila melanogaster

    PubMed Central

    Tachibana, Shin-Ichiro; Touhara, Kazushige; Ejima, Aki

    2015-01-01

    A male-specific component, 11-cis-vaccenyl acetate (cVA) works as an anti-aphrodisiac pheromone in Drosophila melanogaster. The presence of cVA on a male suppresses the courtship motivation of other males and contributes to suppression of male-male homosexual courtship, while the absence of cVA on a female stimulates the sexual motivation of nearby males and enhances the male-female interaction. However, little is known how a male distinguishes the presence or absence of cVA on a target fly from either self-produced cVA or secondhand cVA from other males in the vicinity. In this study, we demonstrate that male flies have keen sensitivity to cVA; therefore, the presence of another male in the area reduces courtship toward a female. This reduced level of sexual motivation, however, could be overcome by pretest odor exposure via olfactory habituation to cVA. Real-time imaging of cVA-responsive sensory neurons using the neural activity sensor revealed that prolonged exposure to cVA decreased the levels of cVA responses in the primary olfactory center. Pharmacological and genetic screening revealed that signal transduction via GABAA receptors contributed to this olfactory habituation. We also found that the habituation experience increased the copulation success of wild-type males in a group. In contrast, transgenic males, in which GABA input in a small subset of local neurons was blocked by RNAi, failed to acquire the sexual advantage conferred by habituation. Thus, we illustrate a novel phenomenon in which olfactory habituation positively affects sexual capability in a competitive environment. PMID:26252206

  10. Olfactory discrimination varies in mice with different levels of α7-nicotinic acetylcholine receptor expression.

    PubMed

    Hellier, Jennifer L; Arevalo, Nicole L; Blatner, Megan J; Dang, An K; Clevenger, Amy C; Adams, Catherine E; Restrepo, Diego

    2010-10-28

    Previous studies have shown that schizophrenics have decreased expression of α7-nicotinic acetylcholine (α7) receptors in the hippocampus and other brain regions, paranoid delusions, disorganized speech, deficits in auditory gating (i.e., inability to inhibit neuronal responses to repetitive auditory stimuli), and difficulties in odor discrimination and detection. Here we use mice with decreased α7 expression that also show a deficit in auditory gating to determine if these mice have similar deficits in olfaction. In the adult mouse olfactory bulb (OB), α7 expression localizes in the glomerular layer; however, the functional role of α7 is unknown. We show that inbred mouse strains (i.e., C3H and C57) with varying α7 expressions (e.g., α7 wild-type [α7+/+], α7 heterozygous knock-out [α7+/-] and α7 homozygous knock-out mice [α7-/-]) significantly differ in odor discrimination and detection of chemically-related odorant pairs. Using [(125)I] α-bungarotoxin (α-BGT) autoradiography, α7 expression was measured in the OB. As previously demonstrated, α-BGT binding was localized to the glomerular layer. Significantly more expression of α7 was observed in C57 α7+/+ mice compared to C3H α7+/+ mice. Furthermore, C57 α7+/+ mice were able to detect a significantly lower concentration of an odor in a mixture compared to C3H α7+/+ mice. Both C57 and C3H α7+/+ mice discriminated between chemically-related odorants sooner than α7+/- or α7-/- mice. These data suggest that α7-nicotinic-receptors contribute strongly to olfactory discrimination and detection in mice and may be one of the mechanisms producing olfactory dysfunction in schizophrenics. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Ontogenetic development of the nervus terminalis in toothed whales. Evidence for its non-olfactory nature.

    PubMed

    Buhl, E H; Oelschläger, H A

    1986-01-01

    For the first time in cetaceans, the development of the terminalis system and its continuity between the olfactory placode and the telencephalon has been demonstrated by light microscopy. In the early development of toothed whales (Odontoceti) this system is partially incorporated within the fila olfactoria which grow out from the olfactory placode. As the peripheral olfactory system is reduced in later stages, a strongly developed ganglionlike structure (terminalis ganglion) remains within the primitive meninx. Peripherally it is connected via the cribriform plate with ganglionic cell clusters near the septal mucosa. Centrally it is attached to the telencephalon (olfactory tubercle, septal region) by several nerve fibre bundles. In contrast to all other mammalian groups, toothed whales and dolphins are anosmatic while being totally adapted to aquatic life. Therefore the remaining ganglion and plexus must have non-olfactory properties. They may be responsible for the autonomic innervation of intracranial arteries and of the large mucous epithelia in the accessory nasal air sacs. The morphology, evolution and functional implications of the terminalis system in odontocetes and other mammals are discussed.

  12. Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABAARs in the Hippocampus in Early Postnatal Sprague Dawley Rats.

    PubMed

    Zheng, Xiaomin; Liang, Liang; Hei, Changchun; Yang, Wenjuan; Zhang, Tingyuan; Wu, Kai; Qin, Yi; Chang, Qing

    2018-04-17

    Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5 μl) or saline (sham, 5 μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n = 6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P < 0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P < 0.01) and increased levels of learned helplessness (P < 0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABA A receptor alpha5 subunit (α5GABA A R) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P < 0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.

  13. Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

    PubMed

    Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

    2016-01-01

    Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

  14. Proteomic Analysis of the Human Olfactory Bulb.

    PubMed

    Dammalli, Manjunath; Dey, Gourav; Madugundu, Anil K; Kumar, Manish; Rodrigues, Benvil; Gowda, Harsha; Siddaiah, Bychapur Gowrishankar; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, Thottethodi Subrahmanya Keshava

    2017-08-01

    The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death. In this context, the olfactory bulb is a vital component of the olfactory system receiving sensory information from the axons of the olfactory receptor neurons located in the nasal cavity and the first place that processes the olfactory information. We report in this study original observations on the human olfactory bulb proteome in healthy subjects, using a high-resolution mass spectrometry-based proteomic approach. We identified 7750 nonredundant proteins from human olfactory bulbs. Bioinformatics analysis of these proteins showed their involvement in biological processes associated with signal transduction, metabolism, transport, and olfaction. These new observations provide a crucial baseline molecular profile of the human olfactory bulb proteome, and should assist the future discovery of biomarker proteins and novel diagnostics associated with diseases characterized by olfactory dysfunction.

  15. Regulation of cyclic nucleotide-gated channels and membrane excitability in olfactory receptor cells by carbon monoxide

    NASA Technical Reports Server (NTRS)

    Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

    1995-01-01

    1. The effect of the putative neural messenger carbon monoxide (CO) and the role of the cGMP second-messenger system for olfactory signal generation was examined in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With the use of whole cell voltage-clamp recordings in combination with a series of ionic and pharmological tests, it is demonstrated that exogenously applied CO is a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels previously described to mediate odor transduction. 3. Several lines of evidence suggest that CO mediates its effect through stimulation of a soluble guanylyl cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion is based on the findings that CO responses show an absolute requirement for guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect of CO on CNG currents in the absence of GTP is detectable, and that a blocker of sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation. This analysis implies that CO is a potent activator of olfactory sGC. 5. Perforated patch recordings using amphotericin B demonstrate that low micromolar doses of CO effectively depolarize the membrane potential of ORNs through tonic activation of CNG channels. This effect in turn regulates excitable and adaptive properties of ORNs and modulates neuronal responsiveness. 6. These data argue for an important role of the cGMP pathway in olfactory signaling and support the idea that CO may function as a diffusible messenger in the olfactory system.

  16. Cell density and intracellular translocation of glucocorticoid receptor-immunoreactive neurons in the kokanee salmon (Oncorhynchus nerka kennerlyi) brain, with an emphasis on the olfactory system.

    PubMed

    Carruth, L L; Jones, R E; Norris, D O

    2000-01-01

    This study tested the hypothesis that neurons in olfactory regions of the kokanee salmon brain contain glucocorticoid receptors. Distribution and neuronal number of glucocorticoid receptor-like immunoreactive (GRir) neurons were identified in the kokanee salmon brain using immunohistochemistry with an antibody to GR (polyclonal rabbit anti-human, dilution 1:1500; and monoclonal mouse, dilution 5 micrograms/ml). Distribution of GRir neurons similar to the mammalian pattern was observed in the brains of sexually immature (n = 8; 4 female and 4 male) as well as spawning (n = 8; 4 female and 4 male) salmon. Olfactory-related areas containing GRir positive neuronal bodies included the internal cell layer of the olfactory bulb, ventral-lateral and lateral parts of the dorsal telencephalon (homologue of the mammalian hippocampus), ventral area of the telencephalon (homologue of the mammalian amygdala), glomerulosus complex of the thalamus, the preoptic area, and inferior lobe of the hypothalamus. The pattern of GRir neuronal distribution in sexually immature and spawning fish was similar. However, spawning fish brains, compared to sexually immature brains, exhibited a significantly greater GRir neuronal number in several olfactory regions in paired immunohistochemical runs. There also were differences in intraneuronal location of GRir in olfactory regions, with staining being predominantly cytoplasmic in sexually immature fish but nuclear in spawning fish. These results are consistent with a role for cortisol in olfactory-mediated homing in kokanee salmon. Although GRir were identified in many nonolfactory regions, the focus of this study is on GRir present in brain regions involved in olfaction. Copyright 2000 Academic Press.

  17. Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates

    PubMed Central

    Niimura, Yoshihito

    2007-01-01

    The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human–mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors. PMID:16607462

  18. Specific mesenchymal/epithelial induction of olfactory receptor, vomeronasal, and gonadotropin-releasing hormone (GnRH) neurons

    PubMed Central

    Rawson, N.E; Lischka, F. W.; Yee, K.K.; Peters, A.Z.; Tucker, E.S.; Meechan, D.W.; Zirlinger, M.; Maynard, T.M.; Burd, G.B.; Dulac, C.; Pevny, L.; LaMantia, A-S.

    2013-01-01

    We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs) and gonadotropin releasing hormone (GnRH) neurons—the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions, specifies the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons. PMID:20503368

  19. Reproduction phase-related expression of GnRH-like immunoreactivity in the olfactory receptor neurons, their projections to the olfactory bulb and in the nervus terminalis in the female Indian major carp Cirrhinus mrigala (Ham.).

    PubMed

    Biju, K C; Singru, Praful S; Schreibman, Martin P; Subhedar, Nishikant

    2003-10-01

    The reproductive biology of the Indian major carp Cirrhinus mrigala is tightly synchronized with the seasonal changes in the environment. While the ovaries show growth from February through June, the fish spawn in July-August to coincide with the monsoon; thereafter the fish pass into the postspawning and resting phases. We investigated the pattern of GnRH immunoreactivity in the olfactory system at regular intervals extending over a period of 35 months. Although no signal was detected in the olfactory organ of fish collected from April through February following year, distinct GnRH-like immunoreactivity appeared in the fish collected in March. Intense immunoreactivity was noticed in several olfactory receptor neurons (ORNs) and their axonal fibers as they extend over the olfactory nerve, spread in the periphery of the olfactory bulb (OB), and terminate in the glomerular layer. Strong immunoreactivity was seen in some fascicles of the medial olfactory tracts extending from the OB to the telencephalon. Some neurons of the ganglion cells of nervus terminalis showed GnRH immunostaining during March; no immunoreactivity was detected at other times of the year. Plexus of GnRH immunoreactive fibers extending throughout the bulb represented a different component of the olfactory system; the fiber density showed a seasonal pattern that could be related to the status of gonadal maturity. While it was highest in the prespawning phase, significant reduction in the fiber density was noticed in the fish of spawning and the following regressive phases. Taken together the data suggest that the GnRH in the olfactory system of C. mrigala may play a major role in translation of the environmental cues and influence the downstream signals leading to the stimulation of the brain-pituitary-ovary axis.

  20. Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.

    PubMed

    Bett, N N; Hinch, S G; Kaukinen, K H; Li, S; Miller, K M

    2018-04-16

    Expression of 12 olfactory genes was analysed in adult sockeye salmon Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from their natal migration route. Variation was found in six of these genes, all of which were olfc olfactory receptors and had lower expression levels in salmon nearing spawning grounds. The results may reflect decreased sensitivity to natal water olfactory cues as these fish are no longer seeking the correct migratory route. The expression of olfactory genes during the olfactory-mediated spawning migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these findings demonstrate a link between migratory behaviours and olfactory plasticity that provides a basis for future molecular research on salmon homing. © 2018 The Fisheries Society of the British Isles.

  1. Changes in the serotonergic system in the main olfactory bulb of rats unilaterally deprived from birth to adulthood.

    PubMed

    Gómez, C; Briñón, J G; Orio, L; Colado, M I; Lawrence, A J; Zhou, F C; Vidal, M; Barbado, M V; Alonso, J R

    2007-02-01

    The serotonergic system plays a key role in the modulation of olfactory processing. The present study examined the plastic response of this centrifugal system after unilateral naris occlusion, analysing both serotonergic afferents and receptors in the main olfactory bulb. After 60 days of sensory deprivation, the serotonergic system exhibited adaptive changes. Olfactory deprivation caused a general increase in the number of fibres immunopositive for serotonin but not of those immunopositive for the serotonin transporter. HPLC data revealed an increase in serotonin levels but not in those of its major metabolite, 5-hydroxyindole acetic acid, resulting in a decrease in the 5-hydroxyindole acetic acid/serotonin ratio. These changes were observed not only in the deprived but also in the contralateral olfactory bulb. Double serotonin-tyrosine hydroxylase immunolabelling revealed that the glomerular regions of the deprived olfactory bulb with a high serotonergic fibre density showed a strong reduction in tyrosine hydroxylase. Finally, the serotonin(2A) receptor distribution density and the number of juxtaglomerular cells immunopositive for serotonin(2A) receptor remained unaltered after olfactory deprivation. Environmental stimulation modulated the serotonergic afferents to the olfactory bulb. Our results indicate the presence of a bilateral accumulation of serotonin in the serotonergic axon network, with no changes in serotonin(2A) receptor density after unilateral olfactory deprivation.

  2. Smelling time: a neural basis for olfactory scene analysis

    PubMed Central

    Ache, Barry W.; Hein, Andrew M.; Bobkov, Yuriy V.; Principe, Jose C.

    2016-01-01

    Behavioral evidence from phylogenetically diverse animals and humans suggests that olfaction could be much more involved in interpreting space and time than heretofore imagined by extracting temporal information inherent in the olfactory signal. If this is the case, the olfactory system must have neural mechanisms capable of encoding time at intervals relevant to the turbulent odor world in which many animals live. We review evidence that animals can use populations of rhythmically active or ‘bursting’ olfactory receptor neurons (bORNs) to extract and encode temporal information inherent in natural olfactory signals. We postulate that bORNs represent an unsuspected neural mechanism through which time can be accurately measured, and that ‘smelling time’ completes the requirements for true olfactory scene analysis. PMID:27594700

  3. Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway.

    PubMed

    Kondoh, Daisuke; Kamikawa, Akihiro; Sasaki, Motoki; Kitamura, Nobuo

    2017-01-01

    Glycoconjugates in the olfactory system play critical roles in neuronal formation, and α1-2 fucose (α1-2Fuc) glycan mediates neurite outgrowth and synaptic plasticity. Histochemical findings of α1-2Fuc glycan in the mouse olfactory system detected using Ulex europaeus agglutinin-I (UEA-I) vary. This study histochemically assessed the main olfactory and vomeronasal pathways in male and female ICR and C57BL/6J mice aged 3-4 months using UEA-I. Ulex europaeus agglutinin-I reacted with most receptor cells arranged mainly at the basal region of the olfactory epithelium. The olfactory nerve layer and glomerular layer of the main olfactory bulb were speckled with positive UEA-I staining, and positive fibers were scattered from the glomerular to the internal plexiform layer. The lateral olfactory tract and rostral migratory stream were also positive for UEA-I. We identified superficial short-axon cells, interneurons of the external plexiform layer, external, middle and internal tufted cells, mitral cells and granule cells as the origins of the UEA-I-positive fibers in the main olfactory bulb. The anterior olfactory nucleus, anterior piriform cortex and olfactory tubercle were negative for UEA-I. Most receptor cells in the vomeronasal epithelium and most glomeruli of the accessory olfactory bulb were positive for UEA-I. Our findings indicated that α1-2Fuc glycan is located within the primary and secondary, but not the ternary, pathways of the main olfactory system, in local circuits of the main olfactory bulb and within the primary, but not secondary, pathway of the vomeronasal system. © 2016 S. Karger AG, Basel.

  4. Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment

    PubMed Central

    Lemons, Kayla; Aoudé, Imad; Ogura, Tatsuya; Mbonu, Kenechukwu; Matsumoto, Ichiro; Arakawa, Hiroyuki

    2017-01-01

    The mammalian main olfactory epithelium (MOE) modifies its activities in response to changes in the chemical environment. This process is essential for maintaining the functions of the olfactory system and the upper airway. However, mechanisms involved in this functional maintenance, especially those occurring via paracrine regulatory pathways within the multicellular MOE, are poorly understood. Previously, a population of non-neuronal, transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) was identified in the MOE, and the initial characterization of these cells showed that they are cholinergic and responsive to various xenobiotics including odorants at high concentrations. Here, we investigated the role of TRPM5-MCs in maintaining olfactory function using transcription factor Skn-1a knockout (Skn-1a-/-) mice, which lack TRPM5-MCs in the MOE. Under our standard housing conditions, Skn-1a-/- mice do not differ significantly from control mice in odor-evoked electro-olfactogram (EOG) responses and olfactory-guided behaviors, including finding buried food and preference reactions to socially and sexually relevant odors. However, after a 2-wk exposure to high-concentration odor chemicals and chitin powder, Skn-1a-/- mice exhibited a significant reduction in their odor and pheromone-evoked EOG responses. Consequently, their olfactory-guided behaviors were impaired compared with vehicle-exposed Skn-1a-/- mice. Conversely, the chemical exposure did not induce significant changes in the EOG responses and olfactory behaviors of control mice. Therefore, our physiological and behavioral results indicate that TRPM5-MCs play a protective role in maintaining the olfactory function of the MOE. PMID:28612045

  5. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

    PubMed

    van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

    2015-01-01

    The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. A Presynaptic Gain Control Mechanism Fine-Tunes Olfactory Behavior

    PubMed Central

    Root, Cory M.; Masuyama, Kaoru; Green, David S.; Enell, Lina E.; Nässel, Dick R.; Lee, Chi-Hon; Wang, Jing W.

    2008-01-01

    Early sensory processing can play a critical role in sensing environmental cues. We have investigated the physiological and behavioral function of gain control at the first synapse of olfactory processing in Drosophila. We report that olfactory receptor neurons (ORNs) express the GABAB receptor (GABABR) and its expression expands the dynamic range of ORN synaptic transmission that is preserved in projection neuron responses. Strikingly, we find that different ORN channels have unique baseline levels of GABABR expression. ORNs that sense the aversive odorant CO2 do not express GABABRs nor exhibit any presynaptic inhibition. In contrast, pheromone-sensing ORNs express a high level of GABABRs and exhibit strong presynaptic inhibition. Furthermore, a behavioral significance of presynaptic inhibition was revealed by a courtship behavior in which pheromone-dependent mate localization is impaired in flies that lack GABABRs in specific ORNs. Together, these findings indicate that different olfactory receptor channels may employ heterogeneous presynaptic gain control as a mechanism to allow an animal’s innate behavioral responses to match its ecological needs. PMID:18667158

  7. Kin recognition in zebrafish: a 24-hour window for olfactory imprinting

    PubMed Central

    Gerlach, Gabriele; Hodgins-Davis, Andrea; Avolio, Carla; Schunter, Celia

    2008-01-01

    Distinguishing kin from non-kin profoundly impacts the evolution of social behaviour. Individuals able to assess the genetic relatedness of conspecifics can preferentially allocate resources towards related individuals and avoid inbreeding. We have addressed the question of how animals acquire the ability to recognize kin by studying the development of olfactory kin preference in zebrafish (Danio rerio). Previously, we showed that zebrafish use an olfactory template to recognize even unfamiliar kin through phenotype matching. Here, we show for the first time that this phenotype matching is based on a learned olfactory imprinting process in which exposure to kin individuals on day 6 post fertilization (pf) is necessary and sufficient for imprinting. Larvae that were exposed to kin before or after but not on day 6 pf did not recognize kin. Larvae isolated from all contact with conspecifics did not imprint on their own chemical cues; therefore, we see no evidence for kin recognition through self-matching in this species. Surprisingly, exposure to non-kin odour during the sensitive phase of development did not result in imprinting on the odour cues of unrelated individuals, suggesting a genetic predisposition to kin odour. Urine-born peptides expressed by genes of the immune system (MHC) are important messengers carrying information about ‘self’ and ‘other’. We suggest that phenotype matching is acquired through a time-sensitive learning process that, in zebrafish, includes a genetic predisposition potentially involving MHC genes expressed in the olfactory receptor neurons. PMID:18544507

  8. Kin recognition in zebrafish: a 24-hour window for olfactory imprinting.

    PubMed

    Gerlach, Gabriele; Hodgins-Davis, Andrea; Avolio, Carla; Schunter, Celia

    2008-09-22

    Distinguishing kin from non-kin profoundly impacts the evolution of social behaviour. Individuals able to assess the genetic relatedness of conspecifics can preferentially allocate resources towards related individuals and avoid inbreeding. We have addressed the question of how animals acquire the ability to recognize kin by studying the development of olfactory kin preference in zebrafish (Danio rerio). Previously, we showed that zebrafish use an olfactory template to recognize even unfamiliar kin through phenotype matching. Here, we show for the first time that this phenotype matching is based on a learned olfactory imprinting process in which exposure to kin individuals on day 6 post fertilization (pf) is necessary and sufficient for imprinting. Larvae that were exposed to kin before or after but not on day 6 pf did not recognize kin. Larvae isolated from all contact with conspecifics did not imprint on their own chemical cues; therefore, we see no evidence for kin recognition through self-matching in this species. Surprisingly, exposure to non-kin odour during the sensitive phase of development did not result in imprinting on the odour cues of unrelated individuals, suggesting a genetic predisposition to kin odour. Urine-born peptides expressed by genes of the immune system (MHC) are important messengers carrying information about 'self' and 'other'. We suggest that phenotype matching is acquired through a time-sensitive learning process that, in zebrafish, includes a genetic predisposition potentially involving MHC genes expressed in the olfactory receptor neurons.

  9. Cell responses to single pheromone molecules may reflect the activation kinetics of olfactory receptor molecules.

    PubMed

    Minor, A V; Kaissling, K-E

    2003-03-01

    Olfactory receptor cells of the silkmoth Bombyx mori respond to single pheromone molecules with "elementary" electrical events that appear as discrete "bumps" a few milliseconds in duration, or bursts of bumps. As revealed by simulation, one bump may result from a series of random openings of one or several ion channels, producing an average inward membrane current of 1.5 pA. The distributions of durations of bumps and of gaps between bumps in a burst can be fitted by single exponentials with time constants of 10.2 ms and 40.5 ms, respectively. The distribution of burst durations is a sum of two exponentials; the number of bumps per burst obeyed a geometric distribution (mean 3.2 bumps per burst). Accordingly the elementary events could reflect transitions among three states of the pheromone receptor molecule: the vacant receptor (state 1), the pheromone-receptor complex (state 2), and the activated complex (state 3). The calculated rate constants of the transitions between states are k(21)=7.7 s(-1), k(23)=16.8 s(-1), and k(32)=98 s(-1).

  10. Temporally diverse firing patterns in olfactory receptor neurons underlie spatiotemporal neural codes for odors

    PubMed Central

    Raman, Baranidharan; Joseph, Joby; Tang, Jeff; Stopfer, Mark

    2010-01-01

    Odorants are represented as spatiotemporal patterns of spikes in neurons of the antennal lobe (AL, insects) and olfactory bulb (OB, vertebrates). These response patterns have been thought to arise primarily from interactions within the AL/OB, an idea supported, in part, by the assumption that olfactory receptor neurons (ORNs) respond to odorants with simple firing patterns. However, activating the AL directly with simple pulses of current evoked responses in AL neurons that were much less diverse, complex, and enduring than responses elicited by odorants. Similarly, models of the AL driven by simplistic inputs generated relatively simple output. How then are dynamic neural codes for odors generated? Consistent with recent results from several other species, our recordings from locust ORNs showed a great diversity of temporal structure. Further, we found that, viewed as a population, many response features of ORNs were remarkably similar to those observed within the AL. Using a set of computational models constrained by our electrophysiological recordings, we found that the temporal heterogeneity of responses of ORNs critically underlies the generation of spatiotemporal odor codes in the AL. A test then performed in vivo confirmed that, given temporally homogeneous input, the AL cannot create diverse spatiotemporal patterns on its own; however, given temporally heterogeneous input, the AL generated realistic firing patterns. Finally, given the temporally structured input provided by ORNs, we clarified several separate, additional contributions of the AL to olfactory information processing. Thus, our results demonstrate the origin and subsequent reformatting of spatiotemporal neural codes for odors. PMID:20147528

  11. An olfactory receptor from Apolygus lucorum (Meyer-Dur) mainly tuned to volatiles from flowering host plants.

    PubMed

    Yan, Shu-Wei; Zhang, Jin; Liu, Yang; Li, Guo-Qing; Wang, Gui-Rong

    2015-08-01

    Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) is one of the most serious agricultural pests, feeding on a wide range of cultivated plants, including cotton, cereals and vegetables in the north of China. This insect can frequently switch between habitats and host plants over seasons and prefer plants in bloom. A. lucorum relies heavily on olfaction to locate its host plants finely discriminating different plant volatiles in the environment. Despite its economical importance, research on the olfactory system of this species has been so far very limited. In this study, we have identified and characterized an olfactory receptor which is sensitively tuned to (Z)-3-Hexenyl acetate and several flowering compounds. Besides being present in the bouquet of some flowers, these compounds are produced by plants that have suffered attacks and are supposed to act as chemical messengers between plants. This OR may play an important role in the selection of host plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Inactivation of the olfactory marker protein (OMP) gene in river dolphins and other odontocete cetaceans.

    PubMed

    Springer, Mark S; Gatesy, John

    2017-04-01

    Various toothed whales (Odontoceti) are unique among mammals in lacking olfactory bulbs as adults and are thought to be anosmic (lacking the olfactory sense). At the molecular level, toothed whales have high percentages of pseudogenic olfactory receptor genes, but species that have been investigated to date retain an intact copy of the olfactory marker protein gene (OMP), which is highly expressed in olfactory receptor neurons and may regulate the temporal resolution of olfactory responses. One hypothesis for the retention of intact OMP in diverse odontocete lineages is that this gene is pleiotropic with additional functions that are unrelated to olfaction. Recent expression studies provide some support for this hypothesis. Here, we report OMP sequences for representatives of all extant cetacean families and provide the first molecular evidence for inactivation of this gene in vertebrates. Specifically, OMP exhibits independent inactivating mutations in six different odontocete lineages: four river dolphin genera (Platanista, Lipotes, Pontoporia, Inia), sperm whale (Physeter), and harbor porpoise (Phocoena). These results suggest that the only essential role of OMP that is maintained by natural selection is in olfaction, although a non-olfactory role for OMP cannot be ruled out for lineages that retain an intact copy of this gene. Available genome sequences from cetaceans and close outgroups provide evidence of inactivating mutations in two additional genes (CNGA2, CNGA4), which imply further pseudogenization events in the olfactory cascade of odontocetes. Selection analyses demonstrate that evolutionary constraints on all three genes (OMP, CNGA2, CNGA4) have been greatly reduced in Odontoceti, but retain a signature of purifying selection on the stem Cetacea branch and in Mysticeti (baleen whales). This pattern is compatible with the 'echolocation-priority' hypothesis for the evolution of OMP, which posits that negative selection was maintained in the common

  13. The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

    PubMed Central

    Milardi, Demetrio; Cacciola, Alberto; Calamuneri, Alessandro; Ghilardi, Maria F.; Caminiti, Fabrizia; Cascio, Filippo; Andronaco, Veronica; Anastasi, Giuseppe; Mormina, Enricomaria; Arrigo, Alessandro; Bruschetta, Daniele; Quartarone, Angelo

    2017-01-01

    Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders. PMID:28443000

  14. Olfactory discrimination ability of CD-1 mice for a large array of enantiomers.

    PubMed

    Laska, M; Shepherd, G M

    2007-01-05

    With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species' olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships.

  15. Olfactory discrimination ability of CD-1 mice for a large array of enantiomers

    PubMed Central

    Laska, Matthias; Shepherd, Gordon M.

    2006-01-01

    With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species′ olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships. PMID:17045753

  16. Activation of β-noradrenergic receptors enhances rhythmic bursting in mouse olfactory bulb external tufted cells.

    PubMed

    Zhou, Fu-Wen; Dong, Hong-Wei; Ennis, Matthew

    2016-12-01

    The main olfactory bulb (MOB) receives a rich noradrenergic innervation from the nucleus locus coeruleus. Despite the well-documented role of norepinephrine and β-adrenergic receptors in neonatal odor preference learning, identified cellular physiological actions of β-receptors in the MOB have remained elusive. β-Receptors are expressed at relatively high levels in the MOB glomeruli, the location of external tufted (ET) cells that exert an excitatory drive on mitral and other cell types. The present study investigated the effects of β-receptor activation on the excitability of ET cells with patch-clamp electrophysiology in mature mouse MOB slices. Isoproterenol and selective β 2 -, but not β 1 -, receptor agonists were found to enhance two key intrinsic currents involved in ET burst initiation: persistent sodium (I NaP ) and hyperpolarization-activated inward (I h ) currents. Together, the positive modulation of these currents increased the frequency and strength of ET cell rhythmic bursting. Rodent sniff frequency and locus coeruleus neuronal firing increase in response to novel stimuli or environments. The increase in ET excitability by β-receptor activation may better enable ET cell rhythmic bursting, and hence glomerular network activity, to pace faster sniff rates during heightened norepinephrine release associated with arousal. Copyright © 2016 the American Physiological Society.

  17. Evolution of trace amine associated receptor (TAAR) gene family in vertebrates: lineage-specific expansions and degradations of a second class of vertebrate chemosensory receptors expressed in the olfactory epithelium.

    PubMed

    Hashiguchi, Yasuyuki; Nishida, Mutsumi

    2007-09-01

    The trace amine-associated receptors (TAARs) form a specific family of G protein-coupled receptors in vertebrates. TAARs were initially considered neurotransmitter receptors, but recent study showed that mouse TAARs function as chemosensory receptors in the olfactory epithelium. To clarify the evolutionary dynamics of the TAAR gene family in vertebrates, near-complete repertoires of TAAR genes and pseudogenes were identified from the genomic assemblies of 4 teleost fishes (zebrafish, fugu, stickleback, and medaka), western clawed frogs, chickens, 3 mammals (humans, mice, and opossum), and sea lampreys. Database searches revealed that fishes had many putatively functional TAAR genes (13-109 genes), whereas relatively small numbers of TAAR genes (3-22 genes) were identified in tetrapods. Phylogenetic analysis of these genes indicated that the TAAR gene family was subdivided into 5 subfamilies that diverged before the divergence of ray-finned fishes and tetrapods. In tetrapods, virtually all TAAR genes were located in 1 specific region of their genomes as a gene cluster; however, in fishes, TAAR genes were scattered throughout more than 2 genomic locations. This possibly reflects a whole-genome duplication that occurred in the common ancestor of ray-finned fishes. Expression analysis of zebrafish and stickleback TAAR genes revealed that many TAARs in these fishes were expressed in the olfactory organ, suggesting the relatively high importance of TAARs as chemosensory receptors in fishes. A possible evolutionary history of the vertebrate TAAR gene family was inferred from the phylogenetic and comparative genomic analyses.

  18. Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

    PubMed

    Mizera, L; Gossrau, G; Hummel, T; Haehner, A

    2017-01-01

    There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without

  19. Activation of postsynaptic GABAB receptors modulates the bursting pattern and synaptic activity of olfactory bulb juxtaglomerular neurons.

    PubMed

    Karpuk, Nikolay; Hayar, Abdallah

    2008-01-01

    Olfactory bulb glomeruli are formed by a network of three major types of neurons collectively called juxtaglomerular (JG) cells, which include external tufted (ET), periglomerular (PG), and short axon (SA) cells. There is solid evidence that gamma-aminobutyric acid (GABA) released from PG neurons presynaptically inhibits glutamate release from olfactory nerve terminals via activation of GABA(B) receptors (GABA(B)-Rs). However, it is still unclear whether ET cells have GABA(B)-Rs. We have investigated whether ET cells have functional postsynaptic GABA(B)-Rs using extracellular and whole cell recordings in olfactory bulb slices. In the presence of fast synaptic blockers (CNQX, APV, and gabazine), the GABA(B)-R agonist baclofen either completely inhibited the bursting or reduced the bursting frequency and increased the burst duration and the number of spikes/burst in ET cells. In the presence of fast synaptic blockers and tetrodotoxin, baclofen induced an outward current in ET cells, suggesting a direct postsynaptic effect. Baclofen reduced the frequency and amplitude of spontaneous EPSCs in PG and SA cells. In the presence of sodium and potassium channel blockers, baclofen reduced the frequency of miniature EPSCs, which were inhibited by the calcium channel blocker cadmium. All baclofen effects were reversed by application of the GABA(B)-R antagonist CGP55845. We suggest that activation of GABA(B)-Rs directly inhibits ET cell bursting and decreases excitatory dendrodendritic transmission from ET to PG and SA cells. Thus the postsynaptic GABA(B)-Rs on ET cells may play an important role in shaping the activation pattern of the glomeruli during olfactory coding.

  20. An olfactory cocktail party: figure-ground segregation of odorants in rodents.

    PubMed

    Rokni, Dan; Hemmelder, Vivian; Kapoor, Vikrant; Murthy, Venkatesh N

    2014-09-01

    In odorant-rich environments, animals must be able to detect specific odorants of interest against variable backgrounds. However, studies have found that both humans and rodents are poor at analyzing the components of odorant mixtures, suggesting that olfaction is a synthetic sense in which mixtures are perceived holistically. We found that mice could be easily trained to detect target odorants embedded in unpredictable and variable mixtures. To relate the behavioral performance to neural representation, we imaged the responses of olfactory bulb glomeruli to individual odors in mice expressing the Ca(2+) indicator GCaMP3 in olfactory receptor neurons. The difficulty of segregating the target from the background depended strongly on the extent of overlap between the glomerular responses to target and background odors. Our study indicates that the olfactory system has powerful analytic abilities that are constrained by the limits of combinatorial neural representation of odorants at the level of the olfactory receptors.

  1. Dock and Pak regulate olfactory axon pathfinding in Drosophila.

    PubMed

    Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey

    2003-04-01

    The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

  2. Ethmoidectomy combined with superior meatus enlargement increases olfactory airflow

    PubMed Central

    Kondo, Kenji; Nomura, Tsutomu; Yamasoba, Tatsuya

    2017-01-01

    Objectives The relationship between a particular surgical technique in endoscopic sinus surgery (ESS) and airflow changes in the post‐operative olfactory region has not been assessed. The present study aimed to compare olfactory airflow after ESS between conventional ethmoidectomy and ethmoidectomy with superior meatus enlargement, using virtual ESS and computational fluid dynamics (CFD) analysis. Study Design Prospective computational study. Materials and Methods Nasal computed tomography images of four adult subjects were used to generate models of the nasal airway. The original preoperative model was digitally edited as virtual ESS by performing uncinectomy, ethmoidectomy, antrostomy, and frontal sinusotomy. The following two post‐operative models were prepared: conventional ethmoidectomy with normal superior meatus (ESS model) and ethmoidectomy with superior meatus enlargement (ESS‐SM model). The calculated three‐dimensional nasal geometries were confirmed using virtual endoscopy to ensure that they corresponded to the post‐operative anatomy observed in the clinical setting. Steady‐state, laminar, inspiratory airflow was simulated, and the velocity, streamline, and mass flow rate in the olfactory region were compared among the preoperative and two postoperative models. Results The mean velocity in the olfactory region, number of streamlines bound to the olfactory region, and mass flow rate were higher in the ESS‐SM model than in the other models. Conclusion We successfully used an innovative approach involving virtual ESS, virtual endoscopy, and CFD to assess postoperative outcomes after ESS. It is hypothesized that the increased airflow to the olfactory fossa achieved with ESS‐SM may lead to improved olfactory function; however, further studies are required. Level of Evidence NA. PMID:28894833

  3. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    NASA Astrophysics Data System (ADS)

    Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

    2016-04-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

  4. The Effect of Olfactory Exposure to Non-Insecticidal Agrochemicals on Bumblebee Foraging Behavior

    PubMed Central

    Sprayberry, Jordanna D. H.; Ritter, Kaitlin A.; Riffell, Jeffrey A.

    2013-01-01

    Declines in bumblebee populations have led to investigations into potential causes – including agrochemical effects on bumblebee physiology. The indirect effects of agrochemicals (i.e. behavior modulation) have been postulated, but rarely directly tested. Olfactory information is critical in mediating bumblebee-floral interactions. As agrochemicals emit volatiles, they may indirectly modify foraging behavior. We tested the effects of olfactory contamination of floral odor by agrochemical scent on foraging activity of Bombus impatiens using two behavioral paradigms: localization of food within a maze and forced-choice preference. The presence of a fungicide decreased bumblebees’ ability to locate food within a maze. Additionally, bumblebees preferred to forage in non-contaminated feeding chambers when offered a choice between control and either fertilizer- or fungicide-scented chambers. PMID:24204608

  5. The effect of olfactory exposure to non-insecticidal agrochemicals on bumblebee foraging behavior.

    PubMed

    Sprayberry, Jordanna D H; Ritter, Kaitlin A; Riffell, Jeffrey A

    2013-01-01

    Declines in bumblebee populations have led to investigations into potential causes - including agrochemical effects on bumblebee physiology. The indirect effects of agrochemicals (i.e. behavior modulation) have been postulated, but rarely directly tested. Olfactory information is critical in mediating bumblebee-floral interactions. As agrochemicals emit volatiles, they may indirectly modify foraging behavior. We tested the effects of olfactory contamination of floral odor by agrochemical scent on foraging activity of Bombus impatiens using two behavioral paradigms: localization of food within a maze and forced-choice preference. The presence of a fungicide decreased bumblebees' ability to locate food within a maze. Additionally, bumblebees preferred to forage in non-contaminated feeding chambers when offered a choice between control and either fertilizer- or fungicide-scented chambers.

  6. Effects of Caffeine on Olfactory Learning in Crickets.

    PubMed

    Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro

    2016-10-01

    Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

  7. Olfactory marker protein is critical for functional maturation of olfactory sensory neurons and development of mother preference

    PubMed Central

    Lee, Anderson C.; He, Jiwei; Ma, Minghong

    2011-01-01

    Survival of many altricial animals critically depends on the sense of smell. Curiously, the olfactory system is rather immature at birth and undergoes a maturation process, which is poorly understood. Using patch clamp technique on mouse olfactory sensory neurons (OSNs) with a defined odorant receptor (OR), we demonstrate that OSNs exhibit functional maturation during the first month of postnatal life by developing faster response kinetics, higher sensitivity, and most intriguingly, higher selectivity. OSNs expressing the receptor MOR23 are relatively broadly tuned in neonates and become selective detectors for the cognate odorant within two weeks. Remarkably, these changes are prevented by genetic ablation of olfactory marker protein (OMP), which is exclusively expressed in mature OSNs. Biochemical and pharmacological evidence supports that alteration in odorant-induced phosphorylation of signaling proteins underlie some of the OMP−/− phenotypes. Furthermore, in a novel behavioral assay in which the mouse pups are given a choice between the biological mother and another unfamiliar lactating female, wild-type pups prefer the biological mother, while OMP knockout pups fail to show preference. These results reveal that OSNs undergo an OMP-dependant functional maturation process that coincides with early development of the smell function, which is essential for pups to form preference for their mother. PMID:21414919

  8. Olfactory Proteins Mediating Chemical Communication in the Navel Orangeworm Moth, Amyelois transitella

    PubMed Central

    Leal, Walter S.; Ishida, Yuko; Pelletier, Julien; Xu, Wei; Rayo, Josep; Xu, Xianzhong; Ames, James B.

    2009-01-01

    Background The navel orangeworm, Amyelois transitella Walker (Lepidoptera: Pyralidae), is the most serious insect pest of almonds and pistachios in California for which environmentally friendly alternative methods of control — like pheromone-based approaches — are highly desirable. Some constituents of the sex pheromone are unstable and could be replaced with parapheromones, which may be designed on the basis of molecular interaction of pheromones and pheromone-detecting olfactory proteins. Methodology By analyzing extracts from olfactory and non-olfactory tissues, we identified putative olfactory proteins, obtained their N-terminal amino acid sequences by Edman degradation, and used degenerate primers to clone the corresponding cDNAs by SMART RACE. Additionally, we used degenerate primers based on conserved sequences of known proteins to fish out other candidate olfactory genes. We expressed the gene encoding a newly identified pheromone-binding protein, which was analyzed by circular dichroism, fluorescence, and nuclear magnetic resonance, and used in a binding assay to assess affinity to pheromone components. Conclusion We have cloned nine cDNAs encoding olfactory proteins from the navel orangeworm, including two pheromone-binding proteins, two general odorant-binding proteins, one chemosensory protein, one glutathione S-transferase, one antennal binding protein X, one sensory neuron membrane protein, and one odorant receptor. Of these, AtraPBP1 is highly enriched in male antennae. Fluorescence, CD and NMR studies suggest a dramatic pH-dependent conformational change, with high affinity to pheromone constituents at neutral pH and no binding at low pH. PMID:19789654

  9. The sox gene Dichaete is expressed in local interneurons and functions in development of the Drosophila adult olfactory circuit.

    PubMed

    Melnattur, Krishna V; Berdnik, Daniela; Rusan, Zeid; Ferreira, Christopher J; Nambu, John R

    2013-02-01

    In insects, the primary sites of integration for olfactory sensory input are the glomeruli in the antennal lobes. Here, axons of olfactory receptor neurons synapse with dendrites of the projection neurons that relay olfactory input to higher brain centers, such as the mushroom bodies and lateral horn. Interactions between olfactory receptor neurons and projection neurons are modulated by excitatory and inhibitory input from a group of local interneurons. While significant insight has been gleaned into the differentiation of olfactory receptor and projection neurons, much less is known about the development and function of the local interneurons. We have found that Dichaete, a conserved Sox HMG box gene, is strongly expressed in a cluster of LAAL cells located adjacent to each antennal lobe in the adult brain. Within these clusters, Dichaete protein expression is detected in both cholinergic and GABAergic local interneurons. In contrast, Dichaete expression is not detected in mature or developing projection neurons, or developing olfactory receptor neurons. Analysis of novel viable Dichaete mutant alleles revealed misrouting of specific projection neuron dendrites and axons, and alterations in glomeruli organization. These results suggest noncell autonomous functions of Dichaete in projection neuron differentiation as well as a potential role for Dichaete-expressing local interneurons in development of the adult olfactory circuitry. Copyright © 2012 Wiley Periodicals, Inc.

  10. Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status.

    PubMed

    Nakahara, Thiago S; Cardozo, Leonardo M; Ibarra-Soria, Ximena; Bard, Andrew D; Carvalho, Vinicius M A; Trintinalia, Guilherme Z; Logan, Darren W; Papes, Fabio

    2016-02-15

    Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors. Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed. Our results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup-oriented behaviors in mice.

  11. Serotonin increases synaptic activity in olfactory bulb glomeruli

    PubMed Central

    Brill, Julia; Shao, Zuoyi; Puche, Adam C.; Wachowiak, Matt

    2016-01-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

  12. Olfactory function in painters exposed to organic solvents.

    PubMed

    Sandmark, B; Broms, I; Löfgren, L; Ohlson, C G

    1989-02-01

    The olfactory receptor cells are in direct contact with the exterior environment, and some chemical agents can impair olfactory function. The olfactory function of 54 painters exposed to organic solvents was compared with that of 42 unexposed referents. A new clinical test validated for the sense of smell was used, the University of Pennsylvania Smell Identification Test. Age, smoking habits, exposure to organic solvents, and medical disorders of importance for the sense of smell were recorded. The painters had a somewhat lower test score than the referents. However, the influence of the exposure variable was not statistically significant in a multiple regression analysis including age and smoking habits. The exposure to organic solvents was low, and therefore an effect of high exposure on olfactory function cannot be ruled out. Since some of the painters had earlier been highly exposed, the effects of high exposure are likely to be reversible.

  13. Mechanisms of Regulation of Olfactory Transduction and Adaptation in the Olfactory Cilium

    PubMed Central

    Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

    2014-01-01

    Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR

  14. HEPATOCYTE GROWTH FACTOR ACTS AS A MITOGEN AND CHEMOATTRACTANT FOR POSTNATAL SUBVENTRICULAR ZONE-OLFACTORY BULB NEUROGENESIS

    PubMed Central

    Wang, Tsu-Wei; Zhang, Huailin; Gyetko, Margaret R.; Parent, Jack M.

    2011-01-01

    Neural progenitor cells persist throughout life in the forebrain subventricular zone (SVZ). They generate neuroblasts that migrate to the olfactory bulb and differentiate into interneurons, but mechanisms underlying these processes are poorly understood. Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic factor that influences cell motility, proliferation and morphogenesis in neural and non-neural tissues. HGF and its receptor, c-Met, are present in the rodent SVZ-olfactory bulb pathway. Using in vitro neurogenesis assays and in vivo studies of partially HGF-deficient mice, we find that HGF promotes SVZ cell proliferation and progenitor cell maintenance, while slowing differentiation and possibly altering cell fate choices. HGF also acts as a chemoattractant for SVZ neuroblasts in co-culture assays. Decreased HGF signaling induces ectopic SVZ neuroblast migration and alters the timing of migration to the olfactory bulb. These results suggest that HGF influences multiple steps in postnatal forebrain neurogenesis. HGF is a mitogen for SVZ neural progenitors, and regulates their differentiation and olfactory bulb migration. PMID:21683144

  15. Role of olfactory bulb serotonin in olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae).

    PubMed

    Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Haupt, Moritz; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2010-09-17

    The role of olfactory bulb (OB) serotonin [5-hydroxytryptamine (5-HT)] in olfactory learning and memory was tested in the greater short-nosed fruit bat, Cynopterus sphinx (family Pteropodidae). Graded concentrations (25, 40, and 60microg) of 5,7-dihydroxytryptamine (5,7-DHT) or saline were injected into the OB of bats one day before training to the novel odor. In a behavioral test, 5,7-DHT (60microg) injected bats made significantly fewer feeding attempts and bouts when compared to saline-injected bats during learning and in the memory test. Subsequent biochemical analysis showed that 5-HT level was effectively depleted in the OB of 5,7-DHT injected bats. To test odor-induced 5-HT mediated changes in 5-HT receptors and second messenger cascade in the OB, we examined the expression of 5-HT receptors and mitogen-activated protein kinase (MAPK)/Erk cascade after training to the novel odor. We found that odor stimulation up-regulated the expression of 5-HT(1A) receptor, Erk1 and Creb1 mRNA, and phosphorylation of ERK1 and CREB1. Odor stimulation failed to induce expression in 5-HT-depleted bats, which is similar to control bats and significantly low compared to saline-treated bats. Together these data revealed that the level of 5-HT in the OB may regulate olfactory learning and memory in C. sphinx through Erk and CREB.

  16. The Biogenic Amine Tyramine and its Receptor (AmTyr1) in Olfactory Neuropils in the Honey Bee (Apis mellifera) Brain

    PubMed Central

    Sinakevitch, Irina T.; Daskalova, Sasha M.; Smith, Brian H.

    2017-01-01

    This article describes the cellular sources for tyramine and the cellular targets of tyramine via the Tyramine Receptor 1 (AmTyr1) in the olfactory learning and memory neuropils of the honey bee brain. Clusters of approximately 160 tyramine immunoreactive neurons are the source of tyraminergic fibers with small varicosities in the optic lobes, antennal lobes, lateral protocerebrum, mushroom body (calyces and gamma lobes), tritocerebrum and subesophageal ganglion (SEG). Our tyramine mapping study shows that the primary sources of tyramine in the antennal lobe and calyx of the mushroom body are from at least two Ventral Unpaired Median neurons (VUMmd and VUMmx) with cell bodies in the SEG. To reveal AmTyr1 receptors in the brain, we used newly characterized anti-AmTyr1 antibodies. Immunolocalization studies in the antennal lobe with anti-AmTyr1 antibodies showed that the AmTyr1 expression pattern is mostly in the presynaptic sites of olfactory receptor neurons (ORNs). In the mushroom body calyx, anti-AmTyr1 mapped the presynaptic sites of uniglomerular Projection Neurons (PNs) located primarily in the microglomeruli of the lip and basal ring calyx area. Release of tyramine/octopamine from VUM (md and mx) neurons in the antennal lobe and mushroom body calyx would target AmTyr1 expressed on ORN and uniglomerular PN presynaptic terminals. The presynaptic location of AmTyr1, its structural similarity with vertebrate alpha-2 adrenergic receptors, and previous pharmacological evidence suggests that it has an important role in the presynaptic inhibitory control of neurotransmitter release. PMID:29114209

  17. Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit.

    PubMed

    Hawkins, Sara J; Weiss, Lukas; Offner, Thomas; Dittrich, Katarina; Hassenklöver, Thomas; Manzini, Ivan

    2017-01-01

    Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB) by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks.

  18. Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

    PubMed Central

    Hawkins, Sara J.; Weiss, Lukas; Offner, Thomas; Dittrich, Katarina; Hassenklöver, Thomas; Manzini, Ivan

    2017-01-01

    Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB) by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks. PMID:29234276

  19. Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

    PubMed

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes.

  20. Neuropeptide Y Enhances Olfactory Mucosa Responses to Odorant in Hungry Rats

    PubMed Central

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes. PMID:23024812

  1. Molecular Basis of Olfactory Chemoreception in the Common Bed Bug, Cimex lectularius.

    PubMed

    Liu, Feng; Chen, Zhou; Liu, Nannan

    2017-04-06

    As one of the most notorious ectoparasites, bed bugs rely heavily on human or animal blood sources for survival, mating and reproduction. Chemoreception, mediated by the odorant receptors on the membrane of olfactory sensory neurons, plays a vital role in their host seeking and risk aversion processes. We investigated the responses of odorant receptors to a large spectrum of semiochemicals, including human odorants and plant-released volatiles and found that strong responses were sparse; aldehydes/ketones were the most efficient stimuli, while carboxylic acids and aliphatics/aromatics were comparatively less effective in eliciting responses from bed bug odorant receptors. In bed bugs, both the odorant identity and concentrations play important roles in determining the strength of these responses. The odor space constructed based on the responses from all the odorant receptors tested revealed that odorants within the same chemical group are widely dispersed while odorants from different groups are intermingled, suggesting the complexity of odorant encoding in the bed bug odorant receptors. This study provides a comprehensive picture of the olfactory coding mechanisms of bed bugs that will ultimately contribute to the design and development of novel olfactory-based strategies to reduce both the biting nuisance and disease transmission from bed bugs.

  2. Molecular Basis of Olfactory Chemoreception in the Common Bed Bug, Cimex lectularius

    PubMed Central

    Liu, Feng; Chen, Zhou; Liu, Nannan

    2017-01-01

    As one of the most notorious ectoparasites, bed bugs rely heavily on human or animal blood sources for survival, mating and reproduction. Chemoreception, mediated by the odorant receptors on the membrane of olfactory sensory neurons, plays a vital role in their host seeking and risk aversion processes. We investigated the responses of odorant receptors to a large spectrum of semiochemicals, including human odorants and plant-released volatiles and found that strong responses were sparse; aldehydes/ketones were the most efficient stimuli, while carboxylic acids and aliphatics/aromatics were comparatively less effective in eliciting responses from bed bug odorant receptors. In bed bugs, both the odorant identity and concentrations play important roles in determining the strength of these responses. The odor space constructed based on the responses from all the odorant receptors tested revealed that odorants within the same chemical group are widely dispersed while odorants from different groups are intermingled, suggesting the complexity of odorant encoding in the bed bug odorant receptors. This study provides a comprehensive picture of the olfactory coding mechanisms of bed bugs that will ultimately contribute to the design and development of novel olfactory-based strategies to reduce both the biting nuisance and disease transmission from bed bugs. PMID:28383033

  3. Refining the dual olfactory hypothesis: pheromone reward and odour experience.

    PubMed

    Martínez-García, Fernando; Martínez-Ricós, Joana; Agustín-Pavón, Carmen; Martínez-Hernández, Jose; Novejarque, Amparo; Lanuza, Enrique

    2009-06-25

    In rodents, sexual advertisement and gender recognition are mostly (if not exclusively) mediated by chemosignals. Specifically, there is ample evidence indicating that female mice are 'innately' attracted by male sexual pheromones that have critical non-volatile components and are detected by the vomeronasal organ. These pheromones can only get access to the vomeronasal organ by active pumping mechanisms that require close contact with the source of the stimulus (e.g. urine marks) during chemoinvestigation. We have hypothesised that male sexual pheromones are rewarding to female mice. Indeed, male-soiled bedding can be used as a reinforcer to induce conditioned place preference, provided contact with the bedding is allowed. The neural mechanisms of pheromone reward seem, however, different from those employed by other natural reinforcers, such as the sweetness or postingestive effects of sucrose. In contrast to vomeronasal-detected male sexual pheromones, male-derived olfactory stimuli (volatiles) are not intrinsically attractive to female mice. However, after repeated exposure to male-soiled bedding, intact female mice develop an acquired preference for male odours. On the contrary, in females whose accessory olfactory bulbs have been lesioned, exposure to male-soiled bedding induces aversion to male odorants. These considerations, together with data on the different properties of olfactory and vomeronasal receptors, lead us to make a proposal for the complementary roles that the olfactory and vomeronasal systems play in intersexual attraction and in other forms of intra- or inter-species communication.

  4. Olfactory Receptor Multigene Family in Vertebrates: From the Viewpoint of Evolutionary Genomics

    PubMed Central

    Niimura, Yoshihito

    2012-01-01

    Olfaction is essential for the survival of animals. Diverse odor molecules in the environment are detected by the olfactory receptors (ORs) in the olfactory epithelium of the nasal cavity. There are ~400 and ~1,000 OR genes in the human and mouse genomes, respectively, forming the largest multigene family in mammals. The relationships between ORs and odorants are multiple-to-multiple, which allows for discriminating almost unlimited number of different odorants by a combination of ORs. However, the OR-ligand relationships are still largely unknown, and predicting the quality of odor from its molecular structure is unsuccessful. Extensive bioinformatic analyses using the whole genomes of various organisms revealed a great variation in number of OR genes among species, reflecting the diversity of their living environments. For example, higher primates equipped with a well-developed vision system and dolphins that are secondarily adapted to the aquatic life have considerably smaller numbers of OR genes than most of other mammals do. OR genes are characterized by extremely frequent gene duplications and losses. The OR gene repertories are also diverse among human individuals, explaining the diversity of odor perception such as the specific anosmia. OR genes are present in all vertebrates. The number of OR genes is smaller in teleost fishes than in mammals, while the diversity is higher in the former than the latter. Because the genome of amphioxus, the most basal chordate species, harbors vertebrate-like OR genes, the origin of OR genes can be traced back to the common ancestor of the phylum Chordata. PMID:23024602

  5. Calcium signals in olfactory neurons.

    PubMed

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  6. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

    PubMed

    Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

    2014-04-02

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

  7. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    PubMed

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

  8. Immunocytochemical characterisation of ensheathing glia in the olfactory and vomeronasal systems of Ambystoma mexicanum (Caudata: Ambystomatidae).

    PubMed

    Lazzari, Maurizio; Bettini, Simone; Franceschini, Valeria

    2016-03-01

    The olfactory and vomeronasal systems of vertebrates are characterised by neurogenesis occurring throughout life. The regenerative ability of olfactory receptor neurons relies on specific glial cells, the olfactory and vomeronasal axon-surrounding cells. Numerous studies have examined mammalian olfactory ensheathing cells which are considered potential candidates for spinal cord injury repair using cell-based therapy. With regard to non-mammalian vertebrates, limited information is available on these glial cells in fish, and there is no information on them in terrestrial anamniotes, the amphibians. In the present research, we studied the immunocytochemical characteristics of axon-surrounding cells in Ambystoma mexicanum. Urodeles have relatively simple olfactory and vomeronasal systems, and represent a good model for studying ensheathing cells in extant representatives of basal tetrapods. Sections from the decalcified heads of A. mexicanum were immunocytochemically processed for the detection of proteins used in research on mammalian olfactory-ensheathing cells. S100, GFAP and NCAM were clearly observed. p75NTR, Gal-1 and PSA-NCAM showed weak staining. No vimentin immunopositivity was observed. The corresponding areas of the olfactory and vomeronasal pathways displayed the same staining characteristics, with the exception of Gal-1, p75NTR and PSA-NCAM in the mucosae. The degree of marker expression was not uniform throughout the sensory pathways. In contrast to fish, both olfactory and vomeronasal nerves displayed uniform staining intensity. This study showed that some markers for mammalian and fish-ensheathing glia are also applicable in urodeles. The olfactory systems of vertebrates show similarities, and also clear dissimilarities. Further investigations are required to ascertain the functional significance of these regional and interspecific differences.

  9. Adiponectin Enhances the Responsiveness of the Olfactory System

    PubMed Central

    Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

    2013-01-01

    The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

  10. Modeling Olfactory Bulb Evolution through Primate Phylogeny

    PubMed Central

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution. PMID:25426851

  11. Olfactory stimulation modulates the blood glucose level in rats.

    PubMed

    Tsuji, Tadataka; Tanaka, Susumu; Bakhshishayan, Sanam; Kogo, Mikihiko; Yamamoto, Takashi

    2018-01-01

    In both humans and animals, chemosensory stimuli, including odors and tastes, induce a variety of physiologic and mental responses related to energy homeostasis, such as glucose kinetics. The present study examined the importance of olfactory function in glucose kinetics following ingestion behavior in a simplified experimental scenario. We applied a conventional glucose tolerance test to rats with and without olfactory function and analyzed subsequent blood glucose (BG) curves in detail. The loss of olfactory input due to experimental damage to the olfactory mucosa induced a marked decrease in the area under the BG curve. Exposure to grapefruit odor and its main component, limonene, both of which activate the sympathetic nerves, before glucose loading also greatly depressed the BG curve. Pre-loading exposure to lavender odor, a parasympathetic activator, stabilized the BG level. These results suggest that olfactory function is important for proper glucose kinetics after glucose intake and that certain fragrances could be utilized as tools for controlling BG levels.

  12. Changes in olfactory bulb volume following lateralized olfactory training.

    PubMed

    Negoias, S; Pietsch, K; Hummel, T

    2017-08-01

    Repeated exposure to odors modifies olfactory function. Consequently, "olfactory training" plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19-43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the "Sniffin' Sticks" test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.

  13. Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior and binding of NMDA receptors in pre-pubertal rats.

    PubMed

    Flores, G; Ibañez-Sandoval, O; Silva-Gómez, A B; Camacho-Abrego, I; Rodríguez-Moreno, A; Morales-Medina, J C

    2014-02-14

    In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX) on behavioral paradigms related to olfaction such as exploratory behavior, locomotor activity in a novel environment and social interaction. We also studied the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors during development. The behavioral effects of nOBX (postnatal day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain regions associated with the olfactory circuitry. A significant increase in the novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested post-pubertally failed to habituate to the novel situation as quickly as the sham- and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in nOBX rats compared with sham-operated and normal controls, while normal exploratory behavior was observed between groups in adulthood. In contrast, social interaction was increased in post-pubertal animals that underwent nOBX. Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre-pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex and outer layer of the cingulate cortex. At post-pubertal age, no significant differences in [(125)I]MK-801 binding were observed between groups at any of the brain regions analyzed. These results suggest that nOBX produces pre-pubertal behavioral disturbances and NMDA receptor changes that are transitory with recovery of olfaction early in adulthood. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

    PubMed Central

    Zhang, Guangfan; Titlow, William B.; Biecker, Stephanie M.; Stromberg, Arnold J.

    2016-01-01

    Abstract A developmental program of epigenetic repression prepares each mammalian olfactory sensory neuron (OSN) to strongly express one allele from just one of hundreds of odorant receptor (OR) genes, but what completes this process of OR gene choice by driving the expression of this allele is incompletely understood. Conditional deletion experiments in mice demonstrate that Lhx2 is necessary for normal expression frequencies of nearly all ORs and all trace amine-associated receptors, irrespective of whether the deletion of Lhx2 is initiated in immature or mature OSNs. Given previous evidence that Lhx2 binds OR gene control elements, these findings indicate that Lhx2 is directly involved in driving OR expression. The data also support the conclusion that OR expression is necessary to allow immature OSNs to complete differentiation and become mature. In contrast to the robust effects of conditional deletion of Lhx2, the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects on Olfr15 expression that reveal independent effects of these two transcription factors. While Lhx2 is necessary for OR expression that supports OR gene choice, Emx2 can act differently; perhaps by helping to control the availability of OR genes for expression. PMID:27822500

  15. Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

    PubMed Central

    Puche, Adam C.; Munger, Steven D.

    2016-01-01

    The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

  16. PI3K-dependent antagonism in mammalian olfactory receptor neurons

    PubMed Central

    Ukhanov, Kirill; Brunert, Daniela; Corey, Elizabeth; Ache, Barry W.

    2011-01-01

    Phosphoinositide (PI) signaling, in particular PI3Kinase (PI3K) signaling, has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand this phenomenon we investigated PI3K-dependent inhibition between single odorant pairs. The concentration-dependent inhibition of the response of native rat ORNs to octanol by citral is PI3K-dependent; blocking PI3K activity with the β and γ isoform-specific inhibitors AS252424 and TGX221 eliminated or strongly reduced the inhibition. Interestingly, blocking PI3K also changed the apparent agonist strength of the otherwise non-competitive antagonist citral. The excitation evoked by citral after blocking PI3K, could be suppressed by the adenylate cyclase III (ACIII) blockers MDL12330A and SQ22536, indicating that citral could also activate ACIII, presumably through the canonical OR. The G protein Gβγ subunit blockers suramin, gallein and M119 suppressed citral’s inhibition of the response to octanol, indicating that the activation of PI3K by citral was G protein dependent, consistent with the idea that inhibition acts through the canonical OR. Lilial similarly antagonized the response to isoamyl acetate in other ORNs, indicating the effect generalizes to at least one other odorant pair. The ability of methyl-isoeugenol, limonene, α-pinene, isovaleric acid and isosafrole to inhibit the response of other ORNs to IBMX/forskolin in a PI3K-dependent manner argues the effect generalizes to yet other structurally dissimilar odorants. Our findings collectively raise the interesting possibility that the OR serves as a molecular logic gate when mammalian ORNs are activated by natural, complex mixtures containing both excitatory and inhibitory odorants. PMID:21209212

  17. The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice

    PubMed Central

    Degl'Innocenti, Andrea

    2016-01-01

    Background In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice. Aim Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice. Procedures Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections. Results In the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a

  18. The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice.

    PubMed

    Degl'Innocenti, Andrea; Parrilla, Marta; Harr, Bettina; Teschke, Meike

    2016-01-01

    In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice. Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice. Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections. In the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings favor Olfr266

  19. Rivastigmine improves hippocampal neurogenesis and depression-like behaviors via 5-HT1A receptor stimulation in olfactory bulbectomized mice.

    PubMed

    Islam, M R; Moriguchi, S; Tagashira, H; Fukunaga, K

    2014-07-11

    Rivastigmine is a non-competitive inhibitor of both acetylcholinesterase (AChE) and butylcholinesterase (BuChE) used to treat mild to moderate dementia in Alzheimer's disease (AD) patients. Although rivastigmine reportedly ameliorates cognitive dysfunction in these patients, its ability to improve Behavioral and Psychological Symptoms of Dementia (BPSD) remains unclear. To determine whether rivastigmine treatment antagonizes depression-like behaviors, we chronically administered rivastigmine (0.1-1.0mg/kg) to olfactory bulbectomized (OBX) mice once a day for 2weeks, starting 2weeks after bulbectomy. Chronic treatment at 0.3 or 1.0mg/kg dose dependently and significantly improved depression-like behaviors, as assessed by tail suspension (TST), forced swim (FST), locomotion and novelty-suppressed feeding (NSFT) tests. Importantly, co-administration with WAY-100635 (1.0mg/kg), a 5-HT1A receptor antagonist, but not ketanserin (1.0mg/kg,), a 5-HT2A receptor antagonist, completely blocked rivastigmine-induced anti-depressive effects, suggesting that 5-HT1A receptor stimulation mediates this activity. Consistent with this observation, rivastigmine treatment significantly rescued impaired neurogenesis observed in OBX mice in a 5-HT1A receptor-dependent manner. Furthermore, enhanced protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation seen following rivastigmine treatment was closely associated with improved neurogenesis. These effects were blocked by WAY-100635 but not ketanserin treatment. Finally, we confirmed that 5-HT1A but not 5-HT2A receptor stimulation by specific agonists mimicked rivastigmine-induced anti-depression activity and promoted hippocampal neurogenesis. We conclude that, in addition to enhancing the cholinergic system, rivastigmine treatment restores normal function of the hippocampal serotonergic system, an activity that likely ameliorates depressive behaviors in AD patients. Copyright © 2014 IBRO. Published by

  20. Extrabulbar olfactory system and nervus terminalis FMRFamide immunoreactive components in Xenopus laevis ontogenesis.

    PubMed

    Pinelli, Claudia; D'Aniello, Biagio; Polese, Gianluca; Rastogi, Rakesh K

    2004-09-01

    The extrabulbar olfactory system (EBOS) is a collection of nerve fibers which originate from primary olfactory receptor-like neurons and penetrate into the brain bypassing the olfactory bulbs. Our description is based upon the application of two neuronal tracers (biocytin, carbocyanine DiI) in the olfactory sac, at the cut end of the olfactory nerve and in the telencephalon of the developing clawed frog. The extrabulbar olfactory system was observed already at stage 45, which is the first developmental stage compatible with our techniques; at this stage, the extrabulbar olfactory system fibers terminated diffusely in the preoptic area. A little later in development, i.e. at stage 50, the extrabulbar olfactory system was maximally developed, extending as far caudally as the rhombencephalon. In the metamorphosing specimens, the extrabulbar olfactory system appeared reduced in extension; caudally, the fiber terminals did not extend beyond the diencephalon. While a substantial overlapping of biocytin/FMRFamide immunoreactivity was observed along the olfactory pathways as well as in the telencephalon, FMRFamide immunoreactivity was never observed to be colocalized in the same cellular or fiber components visualized by tracer molecules. The question whether the extrabulbar olfactory system and the nervus terminalis (NT) are separate anatomical entities or represent an integrated system is discussed.

  1. IP3-gated channels and their occurrence relative to CNG channels in the soma and dendritic knob of rat olfactory receptor neurons.

    PubMed

    Kaur, R; Zhu, X O; Moorhouse, A J; Barry, P H

    2001-05-15

    Olfactory receptor neurons respond to odorants with G protein-mediated increases in the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) and/or inositol-1,4,5-trisphosphate (IP3). This study provides evidence that both second messengers can directly activate distinct ion channels in excised inside-out patches from the dendritic knob and soma membrane of rat olfactory receptor neurons (ORNs). The IP3-gated channels in the dendritic knob and soma membranes could be classified into two types, with conductances of 40 +/- 7 pS (n = 5) and 14 +/- 3 pS (n = 4), with the former having longer open dwell times. Estimated values of the densities of both channels from the same inside-out membrane patches were very much smaller for IP3-gated than for CNG channels. For example, in the dendritic knob membrane there were about 1000 CNG channels x microm(-2) compared to about 85 IP3-gated channels x microm(-2). Furthermore, only about 36% of the dendritic knob patches responded to IP3, whereas 83% of the same patches responded to cAMP. In the soma, both channel densities were lower, with the CNG channel density again being larger ( approximately 57 channels x microm(-2)) than that of the IP3-gated channels ( approximately 13 channels x microm(-2)), with again a much smaller fraction of patches responding to IP3 than to cAMP. These results were consistent with other evidence suggesting that the cAMP-pathway dominates the IP3 pathway in mammalian olfactory transduction.

  2. The styryl dye FM1-43 suppresses odorant responses in a subset of olfactory neurons by blocking cyclic nucleotide-gated (CNG) channels.

    PubMed

    Breunig, Esther; Kludt, Eugen; Czesnik, Dirk; Schild, Detlev

    2011-08-12

    Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.

  3. Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-08-01

    The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.

  4. Multiple functions of GABA A and GABA B receptors during pattern processing in the zebrafish olfactory bulb.

    PubMed

    Tabor, Rico; Yaksi, Emre; Friedrich, Rainer W

    2008-07-01

    gamma-Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABA(A) and GABA(B) receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two-photon Ca2+ imaging. The blockade of GABA(B) receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABA(B) receptors have a modulatory influence on OB output activity. The blockade of GABA(A) receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABA(A) receptor-containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor-dependent neuronal ensembles, and the reorganization of odor-encoding activity patterns. GABA(A) and GABA(B) receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.

  5. Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact

    PubMed Central

    Clark, Jonathan T.; Ray, Anandasankar

    2016-01-01

    Insects have developed highly sophisticated and sensitive olfactory systems to find animal or plant hosts for feeding. Some insects vector pathogens that cause diseases in hundreds of millions of people and destroy billions of dollars of food products every year. There is great interest, therefore, in understanding how the insect olfactory system can be manipulated to reduce their contact with hosts. Here, we review recent advances in our understanding of insect olfactory detection mechanisms, which may serve as a foundation for designing insect control programs based on manipulation of their behaviors by using odorants. Because every insect species has a unique set of olfactory receptors and olfactory-mediated behaviors, we focus primarily on general principles of odor detection that potentially apply to most insects. While these mechanisms have emerged from studies on model systems for study of insect olfaction, such as Drosophila melanogaster, they provide a foundation for discovery of odorants to repel insects or reduce host-seeking behavior. PMID:27628342

  6. Integrating temperature with odor processing in the olfactory bulb.

    PubMed

    Kludt, Eugen; Okom, Camille; Brinkmann, Alexander; Schild, Detlev

    2015-05-20

    Temperature perception has long been classified as a somesthetic function solely. However, in recent years several studies brought evidence that temperature perception also takes place in the olfactory system of rodents. Temperature has been described as an effective stimulus for sensory neurons of the Grueneberg ganglion located at the entrance of the nose. Here, we investigate whether a neuronal trace of temperature stimulation can be observed in the glomeruli and mitral cells of the olfactory bulb, using calcium imaging and fast line-scanning microscopy. We show in the Xenopus tadpole system that the γ-glomerulus, which receives input from olfactory neurons, is highly sensitive to temperature drops at the olfactory epithelium. We observed that thermo-induced activity in the γ-glomerulus is conveyed to the mitral cells innervating this specific neuropil. Surprisingly, a substantial number of thermosensitive mitral cells were also chemosensitive. Moreover, we report another unique feature of the γ-glomerulus: it receives ipsilateral and contralateral afferents. The latter fibers pass through the contralateral bulb, cross the anterior commissure, and then run to the ipsilateral olfactory bulb, where they target the γ-glomerulus. Temperature drops at the contralateral olfactory epithelium also induced responses in the γ-glomerulus and in mitral cells. Temperature thus appears to be a relevant physiological input to the Xenopus olfactory system. Each olfactory bulb integrates and codes temperature signals originating from receptor neurons of the ipsilateral and contralateral nasal cavities. Finally, temperature and chemical information is processed in shared cellular networks. Copyright © 2015 the authors 0270-6474/15/357892-11$15.00/0.

  7. Sadness might isolate you in a non-smelling world: olfactory perception and depression

    PubMed Central

    Schablitzky, Sylvia; Pause, Bettina M.

    2014-01-01

    Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

  8. Male- and female-biased gene expression of olfactory-related genes in the antennae of Asian corn borer, Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae)

    USDA-ARS?s Scientific Manuscript database

    The Asian corn borer (ACB), Ostrinia furnacalis (Guenée), is a destructive pest insect of cultivated corn crops, for which antennal-expressed receptors are important to detect olfactory cues for mate attraction and oviposition. Non-normalized male and female O. furnacalis antennal cDNA libraries we...

  9. Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice

    PubMed Central

    Dong, Frederick N.

    2017-01-01

    Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia- and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type α-helical repeats, which may mediate protein–protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior. SIGNIFICANCE STATEMENT Sensory receptor cells are generally thought to evolve to respond to sensory cues as fast as they can. This idea is consistent with mutational analyses in various sensory systems, where mutations of sensory receptor cells often resulted in reduced response size and slowed response kinetics. Contrary to this idea, we have found that there is a kinetic “damper” present in the olfactory transduction cascade of the mouse that slows down the response kinetics and

  10. Non-conventional features of peripheral serotonin signalling - the gut and beyond.

    PubMed

    Spohn, Stephanie N; Mawe, Gary M

    2017-07-01

    Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

  11. Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

    PubMed Central

    Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

    2009-01-01

    The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

  12. Identification and Characterization of Pheromone Receptors and Interplay between Receptors and Pheromone Binding Proteins in the Diamondback Moth, Plutella xyllostella

    PubMed Central

    Sun, Mengjing; Liu, Yang; Walker, William B.; Liu, Chengcheng; Lin, Kejian; Gu, Shaohua; Zhang, Yongjun; Zhou, Jingjiang; Wang, Guirong

    2013-01-01

    Moths depend on olfactory cues such as sex pheromones to find and recognize mating partners. Pheromone receptors (PRs) and Pheromone binding proteins (PBPs) are thought to be associated with olfactory signal transduction of pheromonal compounds in peripheral olfactory reception. Here six candidate pheromone receptor genes in the diamondback moth, Plutella xyllostella were identified and cloned. All of the six candidate PR genes display male-biased expression, which is a typical characteristic of pheromone receptors. In the Xenopus-based functional study and in situ hybridization, PxylOR4 is defined as another pheromone receptor in addition to the previously characterized PxylOR1. In the study of interaction between PRs and PBPs, PxylPBPs could increase the sensitivity of the complex expressing oocyte cells to the ligand pheromone component while decreasing the sensitivity to pheromone analogs. We deduce that activating pheromone receptors in olfactory receptor neurons requires some role of PBPs to pheromone/PBP complex. If the chemical signal is not the pheromone component, but instead, a pheromone analog with a similar structure, the complex would have a decreased ability to activate downstream pheromone receptors. PMID:23626773

  13. Unitary Responses in Frog Olfactory Epithelium to Sterically Related Molecules at Low Concentrations

    PubMed Central

    Getchell, Thomas V.

    1974-01-01

    Responses of receptor cells in the frog's olfactory epithelium were recorded using platinum-black metal-filled microelectrodes. Spontaneous activity varied over a wide range from 0.07 to 1.8 spikes/s. Mean interspike intervals ranged from 13.7 to 0.5 s. Excitatory responses to six sterically related compounds at low concentrations were investigated. Stimuli were delivered in an aqueous medium. Thresholds for impulse initiation varied from greater than 1 mM down to the nanomolar concentration range. Thresholds of different olfactory receptors to the same stimulus could vary by several log units. Thresholds of the same receptor cell to different stimuli could be within the same order of magnitude, or could vary by as much as 5 log units. Based upon quantitative measures of stimulus-evoked excitatory responses it appeared that some receptors did not discriminate among sterically related molecules, whereas other receptors clearly discriminated between stimuli which evoke similar odor sensations. PMID:4211101

  14. Evidence that thyroid hormone induces olfactory cellular proliferation in salmon during a sensitive period for imprinting.

    PubMed

    Lema, Sean C; Nevitt, Gabrielle A

    2004-09-01

    Salmon have long been known to imprint and home to natal stream odors, yet the mechanisms driving olfactory imprinting remain obscure. The timing of imprinting is associated with elevations in plasma thyroid hormone levels, with possible effects on growth and proliferation of the peripheral olfactory system. Here, we begin to test this idea by determining whether experimentally elevated plasma levels of 3,5,3'-triiodothyronine (T(3)) influence cell proliferation as detected by the 5-bromo-2'-deoxyuridine (BrdU) cell birth-dating technique in the olfactory epithelium of juvenile coho salmon (Oncorhynchus kisutch). We also explore how natural fluctuations in thyroxine (T(4)) relate to proliferation in the epithelium during the parr-smolt transformation. In both studies, we found that BrdU labeled both single and clusters of mitotic cells. The total number of BrdU-labeled cells in the olfactory epithelium was significantly greater in fish with artificially elevated T(3) compared with placebo controls. This difference in proliferation was restricted to the basal region of the olfactory epithelium, where multipotent progenitor cells differentiate into olfactory receptor neurons. The distributions of mitotic cluster sizes differed significantly from a Poisson distribution for both T(3) and placebo treatments, suggesting that proliferation tends to be non-random. Over the course of the parr-smolt transformation, changes in the density of BrdU cells showed a positive relationship with natural fluctuations in plasma T(4). This relationship suggests that even small changes in thyroid activity can stimulate the proliferation of neural progenitor cells in the salmon epithelium. Taken together, our results establish a link between the thyroid hormone axis and measurable anatomical changes in the peripheral olfactory system.

  15. Norepinephrine and Learning-Induced Plasticity in Infant Rat Olfactory System

    PubMed Central

    Sullivan, Regina M.; Wilson, Donald A.; Leon, Michael

    2007-01-01

    Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE β-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE β-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucase (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-lsoproterenol-Propranolol, or (3) Odor only-lsoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. PMID:2585063

  16. Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

    NASA Astrophysics Data System (ADS)

    Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

    In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

  17. The Peripheral Olfactory Repertoire of the Lightbrown Apple Moth, Epiphyas postvittana

    PubMed Central

    Thrimawithana, Amali H.; Crowhurst, Ross N.; Newcomb, Richard D.

    2015-01-01

    The lightbrown apple moth, Epiphyas postvittana is an increasingly global pest of horticultural crops. Like other moths, E. postvittana relies on olfactory cues to locate mates and oviposition sites. To detect these cues, moths have evolved families of genes encoding elements of the peripheral olfactory reception system, including odor carriers, receptors and degrading enzymes. Here we undertake a transcriptomic approach to identify members of these families expressed in the adult antennae of E. postvittana, describing open reading frames encoding 34 odorant binding proteins, 13 chemosensory proteins, 70 odorant receptors, 19 ionotropic receptors, nine gustatory receptors, two sensory neuron membrane proteins, 27 carboxylesterases, 20 glutathione-S-transferases, 49 cytochrome p450s and 18 takeout proteins. For the odorant receptors, quantitative RT-PCR corroborated RNAseq count data on steady state transcript levels. Of the eight odorant receptors that group phylogenetically with pheromone receptors from other moths, two displayed significant male-biased expression patterns, one displayed significant female-biased expression pattern and five were expressed equally in the antennae of both sexes. In addition, we found two male-biased odorant receptors that did not group with previously described pheromone receptors. This suite of olfaction-related genes provides a substantial resource for the functional characterization of this signal transduction system and the development of odor-mediated control strategies for horticultural pests. PMID:26017144

  18. Caffeine and the olfactory bulb.

    PubMed

    Hadfield, M G

    1997-08-01

    Caffeine, a popular CNS stimulant, is the most widely used neuroactive drug. Present in coffee, tea, chocolate, and soft drinks as well as over-the-counter and prescription medications, it influences millions of users. This agent has achieved recent notoriety because its dependency consequences and addictive potential have been re-examined and emphasized. Caffeine's central actions are thought to be mediated through adenosine (A) receptors and monoamine neurotransmitters. The present article suggests that the olfactory bulb (OB) may be an important site in the brain that is responsible for caffeine's central actions in several species. This conclusion is based on the extraordinarily robust and selective effects of caffeine on norepinephrine (NE), dopamine (DA), and particularly serotonin (5HT) utilization in the OB of mice. We believe that these phenomena should be given appropriate consideration as a basis for caffeine's central actions, even in primates. Concurrently, we review a rich rodent literature concerned with A, 5HT, NE, and DA receptors in the OB and related structures along with other monoamine parameters. We also review a more limited literature concerned with the primate OB. Finally, we cite the literature that treats the dependency and addictive effects of caffeine in humans, and relate the findings to possible olfactory mechanisms.

  19. Conventional and Non-Conventional Nuclear Material Signatures

    NASA Astrophysics Data System (ADS)

    Gozani, Tsahi

    2009-03-01

    The detection and interdiction of concealed special nuclear material (SNM) in all modes of transport is one of the most critical security issues facing the United States and the rest of the world. In principle, detection of nuclear materials is relatively easy because of their unique properties: all of them are radioactive and all emit some characteristic gamma rays. A few emit neutrons as well. These signatures are the basis for passive non-intrusive detection of nuclear materials. The low energy of the radiations necessitates additional means of detection and validation. These are provided by high-energy x-ray radiography and by active inspection based on inducing nuclear reactions in the nuclear materials. Positive confirmation that a nuclear material is present or absent can be provided by interrogation of the inspected object with penetrating probing radiation, such as neutrons and photons. The radiation induces specific reactions in the nuclear material yielding, in turn, penetrating signatures which can be detected outside the inspected object. The "conventional" signatures are first and foremost fission signatures: prompt and delayed neutrons and gamma rays. Their intensity (number per fission) and the fact that they have broad energy (non-discrete, though unique) distributions and certain temporal behaviors are key to their use. The "non- conventional" signatures are not related to the fission process but to the unique nuclear structure of each element or isotope in nature. This can be accessed through the excitation of isotopic nuclear levels (discrete and continuum) by neutron inelastic scattering or gamma resonance fluorescence. Finally there is an atomic signature, namely the high atomic number (Z>74), which obviously includes all the nuclear materials and their possible shielding. The presence of such high-Z elements can be inferred by techniques using high-energy x rays. The conventional signatures have been addressed in another article. Non-conventional

  20. Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility.

    PubMed

    Fukuda, Nanaho; Yomogida, Kentaro; Okabe, Masaru; Touhara, Kazushige

    2004-11-15

    Although a subset of the olfactory receptor (OR) gene family is expressed in testis, neither their developmental profile nor their physiological functions have been fully characterized. Here, we show that MOR23 (a mouse OR expressed in the olfactory epithelium and testis) functions as a chemosensing receptor in mouse germ cells. In situ hybridization showed that MOR23 was expressed in round spermatids during stages VI-VIII of spermatogenesis. Lyral, a cognate ligand of MOR23, caused an increase in intracellular Ca2+ in a fraction of spermatogenic cells and spermatozoa. We also generated transgenic mice that express high levels of MOR23 in the testis and examined the response of their germ cells to lyral. The results provided evidence that lyral-induced Ca2+ increases were indeed mediated by MOR23. In a sperm accumulation assay, spermatozoa migrated towards an increasing gradient of lyral. Tracking and sperm flagellar analyses suggest that Ca2+ increases caused by MOR23 activation lead to modulation of flagellar configuration, resulting in chemotaxis. By contrast, a gradient of a cAMP analog or K8.6 solution, which elicit Ca2+ influx in spermatozoa, did not cause sperm accumulation, indicating that chemosensing and regulation of sperm motility was due to an OR-mediated local Ca2+ increase. The present studies indicate that mouse testicular ORs might play a role in chemoreception during sperm-egg communication and thereby regulate fertilization.

  1. Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats.

    PubMed

    Bernal-Mondragón, C; Arriaga-Avila, V; Martínez-Abundis, E; Barrera-Mera, B; Mercado-Gómez, O; Guevara-Guzmán, R

    2017-02-01

    We investigated the short- and long-term effects of extremely low-frequency electromagnetic fields (EMF) on social recognition behavior and expression of α- and β-estrogen receptors (ER). Rats were exposed to 60-Hz electromagnetic fields for 9 or 30 days and tested for social recognition behavior. Immunohistochemistry and western blot assays were performed to evaluate α- and β-ER expression in the olfactory bulb of intact, ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2). Ovariectomization showed impairment of social recognition after 9 days of EMF exposure and a complete recovery after E2 replacement and so did those after 30 days. Short EMF exposure increased expression of β-ER in intact, but not in the others. Longer exposure produced a decrease in intact but an increase in OVX and OVX+E2. Our findings suggest a significant role for β-estrogen receptors and a lack of effect for α-estrogen receptors on a social recognition task. EMF: extremely low frequency electromagnetic fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX + E 2 : ovariectomized + estradiol replacement; IEI: interexposure interval; β-ER: beta estrogen receptor; E 2 : replacement of estradiol; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB: phosphate-buffer.

  2. Morphometric and ultrastructural comparison of the olfactory system in elasmobranchs: the significance of structure-function relationships based on phylogeny and ecology.

    PubMed

    Schluessel, Vera; Bennett, Michael B; Bleckmann, Horst; Blomberg, Simon; Collin, Shaun P

    2008-11-01

    This study investigated the relationship between olfactory morphology, habitat occupancy, and lifestyle in 21 elasmobranch species in a phylogenetic context. Four measures of olfactory capability, that is, the number of olfactory lamellae, the surface area of the olfactory epithelium, the mass of the olfactory bulb, and the mass of the olfactory rosette were compared between individual species and groups, comprised of species with similar habitat and/or lifestyle. Statistical analyses using generalized least squares phylogenetic regression revealed that bentho-pelagic sharks and rays possess significantly more olfactory lamellae and larger sensory epithelial surface areas than benthic species. There was no significant correlation between either olfactory bulb or rosette mass and habitat type. There was also no significant difference between the number of lamellae or the size of the sensory surface area in groups comprised of species with similar diets, that is, groups preying predominantly on crustaceans, cephalopods, echinoderms, polychaetes, molluscs, or teleosts. However, some groups had significantly larger olfactory bulb or rosette masses than others. There was little evidence to support a correlation between phylogeny and morphology, indicating that differences in olfactory capabilities are the result of functional rather than phylogenetic adaptations. All olfactory epithelia exhibited microvilli and cilia, with microvilli in both nonsensory and sensory areas, and cilia only in sensory areas. Cilia over the sensory epithelia originated from supporting cells. In contrast to teleosts, which possess ciliated and microvillous olfactory receptor types, no ciliated olfactory receptor cells were observed. This is the first comprehensive study comparing olfactory morphology to several aspects of elasmobranch ecology in a phylogenetic context.

  3. The vestigial olfactory receptor subgenome of odontocete whales: phylogenetic congruence between gene-tree reconciliation and supermatrix methods.

    PubMed

    McGowen, Michael R; Clark, Clay; Gatesy, John

    2008-08-01

    The macroevolutionary transition of whales (cetaceans) from a terrestrial quadruped to an obligate aquatic form involved major changes in sensory abilities. Compared to terrestrial mammals, the olfactory system of baleen whales is dramatically reduced, and in toothed whales is completely absent. We sampled the olfactory receptor (OR) subgenomes of eight cetacean species from four families. A multigene tree of 115 newly characterized OR sequences from these eight species and published data for Bos taurus revealed a diverse array of class II OR paralogues in Cetacea. Evolution of the OR gene superfamily in toothed whales (Odontoceti) featured a multitude of independent pseudogenization events, supporting anatomical evidence that odontocetes have lost their olfactory sense. We explored the phylogenetic utility of OR pseudogenes in Cetacea, concentrating on delphinids (oceanic dolphins), the product of a rapid evolutionary radiation that has been difficult to resolve in previous studies of mitochondrial DNA sequences. Phylogenetic analyses of OR pseudogenes using both gene-tree reconciliation and supermatrix methods yielded fully resolved, consistently supported relationships among members of four delphinid subfamilies. Alternative minimizations of gene duplications, gene duplications plus gene losses, deep coalescence events, and nucleotide substitutions plus indels returned highly congruent phylogenetic hypotheses. Novel DNA sequence data for six single-copy nuclear loci and three mitochondrial genes (> 5000 aligned nucleotides) provided an independent test of the OR trees. Nucleotide substitutions and indels in OR pseudogenes showed a very low degree of homoplasy in comparison to mitochondrial DNA and, on average, provided more variation than single-copy nuclear DNA. Our results suggest that phylogenetic analysis of the large OR superfamily will be effective for resolving relationships within Cetacea whether supermatrix or gene-tree reconciliation procedures are

  4. Expression of human olfactory receptor 10J5 in heart aorta, coronary artery, and endothelial cells and its functional role in angiogenesis.

    PubMed

    Kim, Sung-Hee; Yoon, Yeo Cho; Lee, Ae Sin; Kang, NaNa; Koo, JaeHyung; Rhyu, Mee-Ra; Park, Jae-Ho

    2015-05-01

    ORs are ectopically expressed in non-chemosensory tissues including muscle, kidney, and keratinocytes; however, their physiological roles are largely unknown. We found that human olfactory receptor 10J5 (OR10J5) is expressed in the human aorta, coronary artery, and umbilical vein endothelial cells (HUVEC). Lyral induces Ca(2+) and phosphorylation of AKT in HUVEC. A knockdown study showed the inhibition of the lyral-induced Ca(2+) and the phosphorylation AKT and implied that these processes are mediated by OR10J5. In addition, lyral enhanced migration of HUVEC, which were also inhibited by RNAi in a migration assay. In addition, matrigel plug assay showed that lyral enhanced angiogenesis in vivo. Together these data demonstrate the physiological role of OR10J5 in angiogenesis and represent roles of ORs in HUVEC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Mixed input to olfactory glomeruli from two subsets of ciliated sensory neurons does not impede relay neuron specificity in the crucian carp.

    PubMed

    Hansson, Kenth-Arne; Døving, Kjell B; Skjeldal, Frode M

    2015-10-01

    The consensus view of olfactory processing is that the axons of receptor-specific primary olfactory sensory neurons (OSNs) converge to a small subset of glomeruli, thus preserving the odour identity before the olfactory information is processed in higher brain centres. In the present study, we show that two different subsets of ciliated OSNs with different odorant specificities converge to the same glomeruli. In order to stain different ciliated OSNs in the crucian carp Carassius carassius we used two different chemical odorants, a bile salt and a purported alarm substance, together with fluorescent dextrans. The dye is transported within the axons and stains glomeruli in the olfactory bulb. Interestingly, the axons from the ciliated OSNs co-converge to the same glomeruli. Despite intermingled innervation of glomeruli, axons and terminal fields from the two different subsets of ciliated OSNs remained mono-coloured. By 4-6 days after staining, the dye was transported trans-synaptically to separately stained axons of relay neurons. These findings demonstrate that specificity of the primary neurons is retained in the olfactory pathways despite mixed innervation of the olfactory glomeruli. The results are discussed in relation to the emerging concepts about non-mammalian glomeruli. © 2015. Published by The Company of Biologists Ltd.

  6. Conventional light chains inhibit the autonomous signaling capacity of the B cell receptor.

    PubMed

    Meixlsperger, Sonja; Köhler, Fabian; Wossning, Thomas; Reppel, Michael; Müschen, Markus; Jumaa, Hassan

    2007-03-01

    Signals from the B cell antigen receptor (BCR), consisting of mu heavy chain (muHC) and conventional light chain (LC), and its precursor the pre-BCR, consisting of muHC and surrogate light chain (SLC), via the adaptor protein SLP-65 regulate the development and function of B cells. Here, we compare the effect of SLC and conventional LC expression on receptor-induced Ca(2+) flux in B cells expressing an inducible form of SLP-65. We found that SLC expression strongly enhanced an autonomous ability of muHC to induce Ca(2+) flux irrespective of additional receptor crosslinking. In contrast, LC expression reduced this autonomous muHC ability and resulted in antigen-dependent Ca(2+) flux. These data indicate that autonomous ligand-independent signaling can be induced by receptor forms other than the pre-BCR. In addition, our data suggest that conventional LCs play an important role in the inhibition of autonomous receptor signaling, thereby allowing further B cell differentiation.

  7. Oxygen control of breathing by an olfactory receptor activated by lactate

    PubMed Central

    Chang, Andy J.; Ortega, Fabian E.; Riegler, Johannes; Madison, Daniel V.; Krasnow, Mark A.

    2015-01-01

    Summary Animals have evolved homeostatic responses to changes in oxygen availability that act on different time scales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long term responses to low oxygen (hypoxia) has been established1, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines2. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation3–6, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline. PMID:26560302

  8. The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input.

    PubMed

    He, Chao; Altshuler-Keylin, Svetlana; Daniel, David; L'Etoile, Noelle D; O'Halloran, Damien

    2016-10-06

    In mammals, olfactory subsystems have been shown to express seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-one-neuron pattern, whereas in Caenorhabditis elegans, olfactory sensory neurons express multiple G-protein coupled odorant receptors per olfactory sensory neuron. In both mammalian and C. elegans olfactory sensory neurons (OSNs), the process of olfactory adaptation begins within the OSN; this process of negative feedback within the mammalian OSN has been well described in mammals and enables activated OSNs to desensitize their response cell autonomously while attending to odors detected by separate OSNs. However, the mechanism that enables C. elegans to adapt to one odor and attend to another odor sensed by the same olfactory sensory neuron remains unclear. We found that the cyclic nucleotide gated channel subunit CNG-1 is required to promote cross adaptation responses between distinct olfactory cues. This change in sensitivity to a pair of odorants after persistent stimulation by just one of these odors is modulated by the internal nutritional state of the animal, and we find that this response is maintained across a diverse range of food sources for C. elegans. We also reveal that CNG-1 integrates food related cues for exploratory motor output, revealing that CNG-1 functions in multiple capacities to link nutritional information with behavioral output. Our data describes a novel model whereby CNG channels can integrate the coincidence detection of appetitive and olfactory information to set olfactory preferences and instruct behavioral outputs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Uptake and transport of manganese in primary and secondary olfactory neurones in pike.

    PubMed

    Tjälve, H; Mejàre, C; Borg-Neczak, K

    1995-07-01

    gamma-spectrometry and autoradiography were used to examine the axoplasmic flow of manganese in the olfactory nerves and to study the uptake of the metal in the brain after application of 54Mn2+ in the olfactory chambers of pikes. The results show that the 54Mn2+ is taken up in the olfactory receptor cells and is transported at a constant rate along the primary olfactory neurones into the brain. The maximal velocity for the transported 54Mn2+ was 2.90 +/- 0.21 mm/hr (mean +/- S.E.) at 10 degrees, which was the temperature used in the experiments. The 54Mn2+ accumulated in the entire olfactory bulbs, although most marked in central and caudal parts. The metal was also seen to migrate into large areas of the telencephalon, apparently mainly via the secondary olfactory axons present in the medial olfactory tract. A transfer along fibres of the medial olfactory tract probably also explains the labelling which was seen in the diencephalon down to the hypothalamus. The results also showed that there is a pathway connecting the two olfactory bulbs of the pike and that this can carry the metal. Our data further showed a marked accumulation of 54Mn2+ in the meningeal epithelium and in the contents of the meningeal sacs surrounding the olfactory bulbs. It appears from our study that manganese has the ability to pass the synaptic junctions between the primary and the secondary olfactory neurones in the olfactory bulbs and to migrate along secondary olfactory pathways into the telencephalon and the diencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules.

    PubMed

    Grison, Alice; Zucchelli, Silvia; Urzì, Alice; Zamparo, Ilaria; Lazarevic, Dejan; Pascarella, Giovanni; Roncaglia, Paola; Giorgetti, Alejandro; Garcia-Esparcia, Paula; Vlachouli, Christina; Simone, Roberto; Persichetti, Francesca; Forrest, Alistair R R; Hayashizaki, Yoshihide; Carloni, Paolo; Ferrer, Isidro; Lodovichi, Claudia; Plessy, Charles; Carninci, Piero; Gustincich, Stefano

    2014-08-27

    The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson's disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown. By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains. Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.

  11. Illuminating odors: when optogenetics brings to light unexpected olfactory abilities

    PubMed Central

    Grimaud, Julien

    2016-01-01

    For hundreds of years, the sense of smell has generated great interest in the world literature, oenologists, and perfume makers but less of scientists. Only recently this sensory modality has gained new attraction in neuroscience when original tools issued from physiology, anatomy, or molecular biology were available to decipher how the brain makes sense of olfactory cues. However, this move was promptly dampened by the difficulties of developing quantitative approaches to study the relationship between the physical characteristics of stimuli and the sensations they create. An upswing of olfactory investigations occurred when genetic tools could be used in combination with devices borrowed from the physics of light (a hybrid technique called optogenetics) to scrutinize the olfactory system and to provide greater physiological precision for studying olfactory-driven behaviors. This review aims to present the most recent studies that have used light to activate components of the olfactory pathway, such as olfactory receptor neurons, or neurons located further downstream, while leaving intact others brain circuits. With the use of optogenetics to unravel the mystery of olfaction, scientists have begun to disentangle how the brain makes sense of smells. In this review, we shall discuss how the brain recognizes odors, how it memorizes them, and how animals make decisions based on odorants they are capable of sensing. Although this review deals with olfaction, the role of light will be central throughout. PMID:27194792

  12. Molecular characterization and histochemical demonstration of salmon olfactory marker protein in the olfactory epithelium of lacustrine sockeye salmon (Oncorhynchus nerka).

    PubMed

    Kudo, H; Doi, Y; Ueda, H; Kaeriyama, M

    2009-09-01

    Despite the importance of olfactory receptor neurons (ORNs) for homing migration, the expression of olfactory marker protein (OMP) is not well understood in ORNs of Pacific salmon (genus Oncorhynchus). In this study, salmon OMP was characterized in the olfactory epithelia of lacustrine sockeye salmon (O. nerka) by molecular biological and histochemical techniques. Two cDNAs encoding salmon OMP were isolated and sequenced. These cDNAs both contained a coding region encoding 173 amino acid residues, and the molecular mass of the two proteins was calculated to be 19,581.17 and 19,387.11Da, respectively. Both amino acid sequences showed marked homology (90%). The protein and nucleotide sequencing demonstrates the existence of high-level homology between salmon OMPs and those of other teleosts. By in situ hybridization using a digoxigenin-labeled salmon OMP cRNA probe, signals for salmon OMP mRNA were observed preferentially in the perinuclear regions of the ORNs. By immunohistochemistry using a specific antibody to salmon OMP, OMP-immunoreactivities were noted in the cytosol of those neurons. The present study is the first to describe cDNA cloning of OMP in salmon olfactory epithelium, and indicate that OMP is a useful molecular marker for the detection of the ORNs in Pacific salmon.

  13. Early olfactory environment influences social behaviour in adult Octodon degus.

    PubMed

    Márquez, Natalia; Martínez-Harms, Jaime; Vásquez, Rodrigo A; Mpodozis, Jorge

    2015-01-01

    We evaluated the extent to which manipulation of early olfactory environment can influence social behaviours in the South American Hystricognath rodent Octodon degus. The early olfactory environment of newborn degus was manipulated by scenting all litter members with eucalyptol during the first month of life. The social behaviour of sexually mature animals (5-7 months old) towards conspecifics was then assessed using a y-maze to compare the response of control (naïve) and treated animals to two different olfactory configurations (experiment 1): (i) a non-familiarized conspecific impregnated with eucalyptol (eucalyptol arm) presented against (ii) a non-familiarized unscented conspecific (control arm). In addition, in dyadic encounters, we assessed the behaviour of control and eucalyptol treated animals towards a non-familiarized conspecific scented with eucalyptol (experiment 2). We found that control subjects explored and spent significantly less time in the eucalyptol arm, indicating neophobic behaviours towards the artificially scented conspecific. Treated subjects explored and spent similar time in both arms of the maze, showing the same interest for both olfactory stimuli presented. During dyadic encounters in experiment 2, an interaction effect between early experience and sex was observed. Control males escaped and avoided their scented partner more frequently than eucalyptol treated male subjects and than females. Both groups did not differ in the exploration of their scented partners, suggesting that avoidance within agonistic context does not relate to neophobic behaviours. Our results suggest that the exposure to eucalyptol during early ontogeny decreases evasive behaviours within an agonistic context as a result of olfactory learning. Altogether, these results indicate that olfactory cues learned in early ontogeny can influence olfactory-guided behaviours in adult degus.

  14. Cross-adaptation between Olfactory Responses Induced by Two Subgroups of Odorant Molecules

    PubMed Central

    Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

    2003-01-01

    It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at −54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 ± 7 mV (mean ± SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:12939391

  15. Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

    PubMed

    Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

    2003-09-01

    It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

  16. Ultrastructural characterisation of the olfactory mucosa of the armadillo Dasypus hybridus (Dasypodidae, Xenarthra)

    PubMed Central

    FERRARI, C. C.; CARMANCHAHI, P. D.; ALDANA MARCOS, H. J.; AFFANNI, J. M.

    2000-01-01

    The ultrastructure of the olfactory mucosa of the armadillo Dasypus hybridus was studied. A comparison with the olfactory mucosa of another armadillo (Chaetophractus villosus) was made. The olfactory mucosa of D. hybridus shows many features which are similar to those of other mammals. Interestingly, it differs from the olfactory mucosa of the armadillo C. villosus. A suggestion is made that these differences may be due to differences in the digging habits of these species. In Dasypus, the supporting cells (SCs) showed dense vacuoles, multivesicular bodies and lysosome-like bodies probably related with the endocytotic system. The SCs show a dense network of SER presumably associated with xenobiotic mechanisms. The olfactory receptor neurons exhibit lysosome-like bodies and multivesicular bodies in their perikarya. These organelles suggest the presence of an endocytotic system. Duct cells of Bowman's glands exhibit secretory activities. Bowman's glands are compound-branched tubulo-acinar mixed glands with merocrine secretory mechanisms. PMID:10739023

  17. Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta.

    PubMed

    Kim, Na Na; Choi, Young Jae; Lim, Sang-Gu; Jeong, Minhwan; Jin, Deuk-Hee; Choi, Cheol Young

    2015-09-01

    Studies of memory formation have recently concentrated on the possible role of N-methyl-d-aspartate receptors (NRs). We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using quantitative polymerase chain reaction (QPCR) during salinity change (seawater→50% seawater→freshwater). NRs were significantly detected in the diencephalon and telencephalon and OR was significantly detected in the olfactory epithelium. The expression of NRs, OR, and ACTH increased after the transition to freshwater. We also determined that treatment with MK-801, an antagonist of NRs, decreased NRs in telencephalon cells. In addition, a reduction in salinity was associated with increased levels of dopamine, ACTH, and cortisol (in vivo). Reductions in salinity evidently caused NRs and OR to increase the expression of cortisol and dopamine. We concluded that memory capacity and olfactory imprinting of salmon is related to the salinity of the environment during the migration to spawning sites. Furthermore, salinity affects the memory/imprinting and olfactory abilities, and cortisol and dopamine is also related with olfactory-related memories during migration. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Identification of Putative Olfactory Genes from the Oriental Fruit Moth Grapholita molesta via an Antennal Transcriptome Analysis

    PubMed Central

    Li, Yiping; Wu, Junxiang

    2015-01-01

    Background The oriental fruit moth, Grapholita molesta, is an extremely important oligophagous pest species of stone and pome fruits throughout the world. As a host-switching species, adult moths, especially females, depend on olfactory cues to a large extent in locating host plants, finding mates, and selecting oviposition sites. The identification of olfactory genes can facilitate investigation on mechanisms for chemical communications. Methodology/Principal Finding We generated transcriptome of female antennae of G.molesta using the next-generation sequencing technique, and assembled transcripts from RNA-seq reads using Trinity, SOAPdenovo-trans and Abyss-trans assemblers. We identified 124 putative olfactory genes. Among the identified olfactory genes, 118 were novel to this species, including 28 transcripts encoding for odorant binding proteins, 17 chemosensory proteins, 48 odorant receptors, four gustatory receptors, 24 ionotropic receptors, two sensory neuron membrane proteins, and one odor degrading enzyme. The identified genes were further confirmed through semi-quantitative reverse transcription PCR for transcripts coding for 26 OBPs and 17 CSPs. OBP transcripts showed an obvious antenna bias, whereas CSP transcripts were detected in different tissues. Conclusion Antennal transcriptome data derived from the oriental fruit moth constituted an abundant molecular resource for the identification of genes potentially involved in the olfaction process of the species. This study provides a foundation for future research on the molecules involved in olfactory recognition of this insect pest, and in particular, the feasibility of using semiochemicals to control this pest. PMID:26540284

  19. Calmodulin as a downstream gene of octopamine-OAR α1 signalling mediates olfactory attraction in gregarious locusts.

    PubMed

    Xu, L; Li, L; Yang, P; Ma, Z

    2017-02-01

    The migratory locust (Locusta migratoria) shows aggregative traits in nymph marching bands and swarm formations through mutual olfactory attraction of conspecifics. However, olfactory preference in different nymph stages in gregarious locusts is not sufficiently explored. In this study, we found that the nymph olfactory preference for gregarious volatiles exhibited obvious variations at different developmental stages. The gregarious locusts show attractive response to conspecific volatiles from the third stadium. Transcriptome comparison between third- and fourth-stadium nymphs showed that the G protein-coupled receptor (GPCR) pathways are significantly enriched. Amongst the genes present in GPCR pathways, the expression level of calmodulin in locust brains significantly increased from the third- to the fourth-stadium nymphs. Amongst the four octopamine receptors (OARs) belonging to the GPCR family, only OAR α1 showed similar expression patterns to those of calmodulin, and knockdown of OAR α1 reduced the expression level of calmodulin. RNA interference of calmodulin decreased locomotion and induced the loss of olfactory attraction in gregarious locusts. Moreover, the activation of OAR α1 in calmodulin-knockdown locusts did not induce olfactory attraction of the nymphs to gregarious volatiles. Thus, calmodulin as a downstream gene of octopamine-OAR α1 (OA-OAR α1) signalling mediates olfactory attraction in gregarious locusts. Overall, this study provides novel insights into the mechanism of OA-OAR α1 signalling involved in olfactory attraction of gregarious locusts. © 2016 The Royal Entomological Society.

  20. Olfactory discrimination predicts cognitive decline among community-dwelling older adults

    PubMed Central

    Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

    2012-01-01

    The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

  1. Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

    PubMed

    Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

    2012-05-22

    The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

  2. Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

    PubMed Central

    Etgen, Anne M.; Dobrenis, Kostantin; Pollard, Jeffrey W.

    2011-01-01

    The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1op) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure. PMID:22046273

  3. Peripheral and Central Olfactory Tuning in a Moth

    PubMed Central

    Ong, Rose C.

    2012-01-01

    Animals can be innately attracted to certain odorants. Because these attractants are particularly salient, they might be expected to induce relatively strong responses throughout the olfactory pathway, helping animals detect the most relevant odors but limiting flexibility to respond to other odors. Alternatively, specific neural wiring might link innately preferred odors to appropriate behaviors without a need for intensity biases. How nonpheromonal attractants are processed by the general olfactory system remains largely unknown. In the moth Manduca sexta, we studied this with a set of innately preferred host plant odors and other, neutral odors. Electroantennogram recordings showed that, as a population, olfactory receptor neurons (ORNs) did not respond with greater intensity to host plant odors, and further local field potential recordings showed that no specific amplification of signals induced by host plant odors occurred between the first olfactory center and the second. Moreover, when odorants were mutually diluted to elicit equally intense output from the ORNs, moths were able to learn to associate all tested odorants equally well with food reward. Together, these results suggest that, although nonpheromonal host plant odors activate broadly distributed responses, they may be linked to attractive behaviors mainly through specific wiring in the brain. PMID:22362866

  4. The activity-dependent histone variant H2BE modulates the life span of olfactory neurons

    PubMed Central

    Santoro, Stephen W; Dulac, Catherine

    2012-01-01

    We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. DOI: http://dx.doi.org/10.7554/eLife.00070.001 PMID:23240083

  5. Spatial distribution of calcium-gated chloride channels in olfactory cilia.

    PubMed

    French, Donald A; Badamdorj, Dorjsuren; Kleene, Steven J

    2010-12-30

    In vertebrate olfactory receptor neurons, sensory cilia transduce odor stimuli into changes in neuronal membrane potential. The voltage changes are primarily caused by the sequential openings of two types of channel: a cyclic-nucleotide-gated (CNG) cationic channel and a calcium-gated chloride channel. In frog, the cilia are 25 to 200 µm in length, so the spatial distributions of the channels may be an important determinant of odor sensitivity. To determine the spatial distribution of the chloride channels, we recorded from single cilia as calcium was allowed to diffuse down the length of the cilium and activate the channels. A computational model of this experiment allowed an estimate of the spatial distribution of the chloride channels. On average, the channels were concentrated in a narrow band centered at a distance of 29% of the ciliary length, measured from the base of the cilium. This matches the location of the CNG channels determined previously. This non-uniform distribution of transduction proteins is consistent with similar findings in other cilia. On average, the two types of olfactory transduction channel are concentrated in the same region of the cilium. This may contribute to the efficient detection of weak stimuli.

  6. Evolution of Acid-Sensing Olfactory Circuits in Drosophilids.

    PubMed

    Prieto-Godino, Lucia L; Rytz, Raphael; Cruchet, Steeve; Bargeton, Benoîte; Abuin, Liliane; Silbering, Ana F; Ruta, Vanessa; Dal Peraro, Matteo; Benton, Richard

    2017-02-08

    Animals adapt their behaviors to specific ecological niches, but the genetic and cellular basis of nervous system evolution is poorly understood. We have compared the olfactory circuits of the specialist Drosophila sechellia-which feeds exclusively on Morinda citrifolia fruit-with its generalist cousins D. melanogaster and D. simulans. We show that D. sechellia exhibits derived odor-evoked attraction and physiological sensitivity to the abundant Morinda volatile hexanoic acid and characterize how the responsible sensory receptor (the variant ionotropic glutamate receptor IR75b) and attraction-mediating circuit have evolved. A single amino acid change in IR75b is sufficient to recode it as a hexanoic acid detector. Expanded representation of this sensory pathway in the brain relies on additional changes in the IR75b promoter and trans-acting loci. By contrast, higher-order circuit adaptations are not apparent, suggesting conserved central processing. Our work links olfactory ecology to structural and regulatory genetic changes influencing nervous system anatomy and function. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. From chemical neuroanatomy to an understanding of the olfactory system

    PubMed Central

    Oboti, L.; Peretto, P.; De Marchis, S.; Fasolo, A.

    2011-01-01

    The olfactory system of mammals is the appropriate model for studying several aspects of neuronal physiology spanning from the developmental stage to neural network remodelling in the adult brain. Both the morphological and physiological understanding of this system were strongly supported by classical histochemistry. It is emblematic the case of the Olfactory Marker Protein (OMP) staining, the first, powerful marker for fully differentiated olfactory receptor neurons and a key tool to investigate the dynamic relations between peripheral sensory epithelia and central relay regions given its presence within olfactory fibers reaching the olfactory bulb (OB). Similarly, the use of thymidine analogues was able to show neurogenesis in an adult mammalian brain far before modern virus labelling and lipophilic tracers based methods. Nowadays, a wealth of new histochemical techniques combining cell and molecular biology approaches is available, giving stance to move from the analysis of the chemically identified circuitries to functional research. The study of adult neurogenesis is indeed one of the best explanatory examples of this statement. After defining the cell types involved and the basic physiology of this phenomenon in the OB plasticity, we can now analyze the role of neurogenesis in well testable behaviours related to socio-chemical communication in rodents. PMID:22297441

  8. Gross anatomy and histology of the olfactory rosette of the shark Heptranchias perlo.

    PubMed

    Ferrando, Sara; Gallus, Lorenzo; Amaroli, Andrea; Gambardella, Chiara; Waryani, Baradi; Di Blasi, Davide; Vacchi, Marino

    2017-06-01

    Sharks belonging to the family Hexanchidae have six or seven gill slits, unlike all other elasmobranchs, which have five gill slits. Their olfactory organs have a round shape, which is common for holocephalans, but not for elasmobranchs. Thus, the shape of the olfactory organ represents a further, less striking, peculiarity of this family among elasmobranchs. Despite that, the microscopic anatomy and histology of the olfactory organ have not yet been studied in any species of this family. Here, an anatomical and histological description of the olfactory organ of the sharpnose sevengill shark Heptranchias perlo is given. The organ is a rosette, with a central raphe and 31-34 primary lamellae, which bear secondary lamellae with a more or less branched shape. The elastic connective capsule which envelops the olfactory rosette possibly changes its shape along with water influx. In the olfactory epithelium, the supporting cells also have a secretory function, while no specialized mucous cells are visible; regarding this feature the olfactory epithelium of H. perlo differs from that of other chondrichthyan species. The immunohistochemical investigation of the sensory epithelium shows the absence of immunoreactivity for Gαolf in receptor neurons, which confirms previous observations in Chondrichthyes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Evaluation of the Role of G Protein-Coupled Receptor Kinase 3 in Desensitization of Mouse Odorant Receptors in a Mammalian Cell Line and in Olfactory Sensory Neurons

    PubMed Central

    Kato, Aya; Reisert, Johannes; Ihara, Sayoko; Yoshikawa, Keiichi

    2014-01-01

    Thousands of odors are sensed and discriminated by G protein-coupled odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). G protein-coupled receptor kinases (GRKs) may have a role in desensitization of ORs. However, whether ORs are susceptible to agonist-dependent desensitization and whether GRKs affect odorant responsiveness of OSNs are currently unknown. Here we show that GRK3 attenuated the agonist responsiveness of a specific mouse odorant receptor for eugenol (mOR-EG) upon agonist pretreatment in HEK293 cells, but GRK3 did not affect the response amplitude or the recovery kinetics upon repeated agonist stimulation. We performed electrophysiological recordings of single OSNs which expressed mOR-EG and green fluorescent protein (GFP) in the presence or absence of GRK3. The kinetics and amplitude of agonist responsiveness of individual GFP-labeled mOR-EG neurons were not significantly affected by the absence of GRK3. These results indicate that the role of GRK3 in attenuating ORs responsiveness in OSNs may have been overestimated. PMID:25313015

  10. [Olfactory sensory perception].

    PubMed

    Fuentes, Aler; Fresno, María Javiera; Santander, Hugo; Valenzuela, Saúl; Gutiérrez, Mario Felipe; Miralles, Rodolfo

    2011-03-01

    The five senses have had a fundamental importance for survival and socialization of human beings. From an evolutionary point of view the sense of smell is the oldest. This sense has a strong representation within the genome, allowing the existence of many types of receptors that allow us to capture multiple volatile odor producing molecules, sending electrical signals to higher centers to report the outside world. Several cortical areas are activated in the brain, which are interconnected to form an extensive and complex neural network, linking for example, areas involved with memory and emotions, thus giving this sense of perceptual richness. While the concept of flavor is largely related to the sense of taste, smell provides the necessary integration with the rest of the senses and higher functions. Fully understanding the sense of smell is relevant to health professionals. Knowing the characteristics of the receptors, the transduction processes and convergence of information in the higher centers involved, we can properly detect olfactory disorders in our patients.

  11. An olfactory demography of a diverse metropolitan population.

    PubMed

    Keller, Andreas; Hempstead, Margaret; Gomez, Iran A; Gilbert, Avery N; Vosshall, Leslie B

    2012-10-10

    Human perception of the odour environment is highly variable. People vary both in their general olfactory acuity as well as in if and how they perceive specific odours. In recent years, it has been shown that genetic differences contribute to variability in both general olfactory acuity and the perception of specific odours. Odour perception also depends on other factors such as age and gender. Here we investigate the influence of these factors on both general olfactory acuity and on the perception of 66 structurally and perceptually different odours in a diverse subject population. We carried out a large human olfactory psychophysics study of 391 adult subjects in metropolitan New York City, an ethnically and culturally diverse North American metropolis. 210 of the subjects were women and the median age was 34.6 years (range 19-75). We recorded ~2,300 data points per subject to obtain a comprehensive perceptual phenotype, comprising multiple perceptual measures of 66 diverse odours. We show that general olfactory acuity correlates with gender, age, race, smoking habits, and body type. Young, female, non-smoking subjects had the highest average olfactory acuity. Deviations from normal body type in either direction were associated with decreased olfactory acuity. Beyond these factors we also show that, surprisingly, there are many odour-specific influences of race, age, and gender on olfactory perception. We show over 100 instances in which the intensity or pleasantness perception of an odour is significantly different between two demographic groups. These data provide a comprehensive snapshot of the olfactory sense of a diverse population. Olfactory acuity in the population is most strongly influenced by age, followed by gender. We also show a large number of diverse correlations between demographic factors and the perception of individual odours that may reflect genetic differences as well as different prior experiences with these odours between demographic groups.

  12. Innate responses to putative ancestral hosts: is the attraction of Western flower thrips to pine pollen a result of relict olfactory receptors?

    PubMed

    Abdullah, Zayed S; Ficken, Katherine J; Greenfield, Bethany P J; Butt, Tariq M

    2014-06-01

    Pollinophagy is widely documented in the order Thysanoptera, with representative individuals from six of the nine divergent families known to feed on pollen. Various pollens of the genus Pinus increase the development time, fecundity, longevity, and settling preference of Western Flower Thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Certain species of flower thrips discriminate among pollen types, but no studies have elucidated the olfactory cues that play a role in their pollen preferences. In this study, the volatile organic compounds emitted by pollens of the genus Pinus were elucidated. Various chemicals from pollen headspace elicited electrophysiological responses from WFT antennae. The compound (S)-(-)-verbenone, identified in pollen headspace, attracted WFT in a 4-arm olfactometer. This compound has potential for use in integrated pest management programs against the pest. We present the hypothesis that this polyphagous insect may have retained ancestral 'relict' olfactory receptors through the course of evolution, to explain this attraction to pine pollen. This attraction has allowed the insect to find and exploit an unusual nutrient source that significantly increases its fitness. The study demonstrates how fossil record analysis and subsequent evolutionary knowledge can aid in explaining possibilities as to why some insects sense and respond to chemicals that would otherwise seem peculiar to their ecology, allowing insight into the evolutionary forces that may shape insect olfactory systems over time.

  13. Molecular Characterization and Differential Expression of Olfactory Genes in the Antennae of the Black Cutworm Moth Agrotis ipsilon

    PubMed Central

    Gu, Shao-Hua; Sun, Liang; Yang, Ruo-Nan; Wu, Kong-Ming; Guo, Yu-Yuan; Li, Xian-Chun; Zhou, Jing-Jiang; Zhang, Yong-Jun

    2014-01-01

    Insects use their sensitive and selective olfactory system to detect outside chemical odorants, such as female sex pheromones and host plant volatiles. Several groups of olfactory proteins participate in the odorant detection process, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs) and sensory neuron membrane proteins (SNMPs). The identification and functional characterization of these olfactory proteins will enhance our knowledge of the molecular basis of insect chemoreception. In this study, we report the identification and differential expression profiles of these olfactory genes in the black cutworm moth Agrotis ipsilon. In total, 33 OBPs, 12 CSPs, 42 ORs, 24 IRs, 2 SNMPs and 1 gustatory receptor (GR) were annotated from the A. ipsilon antennal transcriptomes, and further RT-PCR and RT-qPCR revealed that 22 OBPs, 3 CSPs, 35 ORs, 14 IRs and the 2 SNMPs are uniquely or primarily expressed in the male and female antennae. Furthermore, one OBP (AipsOBP6) and one CSP (AipsCSP2) were exclusively expressed in the female sex pheromone gland. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs were suggested to be responsible for pheromone and general odorant detection and thus could be meaningful target genes for us to study their biological functions in vivo and in vitro. PMID:25083706

  14. Olfactory Performance Is Predicted by Individual Sex-Atypicality, but Not Sexual Orientation

    PubMed Central

    Nováková, Lenka; Varella Valentová, Jaroslava; Havlíček, Jan

    2013-01-01

    Many previous studies have reported robust sex differences in olfactory perception. However, both men and women can be expected to vary in the degree to which they exhibit olfactory performance considered typical of their own or the opposite sex. Sex-atypicality is often described in terms of childhood gender nonconformity, which, however, is not a perfect correlate of non-heterosexual orientation. Here we explored intrasexual variability in psychophysical olfactory performance in a sample of 156 individuals (83 non-heterosexual) and found the lowest odor identification scores in heterosexual men. However, when childhood gender nonconformity was entered in the model along with sexual orientation, better odor identification scores were exhibited by gender-nonconforming men, and greater olfactory sensitivity by gender-conforming women, irrespective of their sexual orientation. Thus, sex-atypicality, but not sexual orientation predicts olfactory performance, and we propose that this might not be limited to olfaction, but represent a more general phenomenon. PMID:24244657

  15. Olfactory performance is predicted by individual sex-atypicality, but not sexual orientation.

    PubMed

    Nováková, Lenka; Varella Valentová, Jaroslava; Havlíček, Jan

    2013-01-01

    Many previous studies have reported robust sex differences in olfactory perception. However, both men and women can be expected to vary in the degree to which they exhibit olfactory performance considered typical of their own or the opposite sex. Sex-atypicality is often described in terms of childhood gender nonconformity, which, however, is not a perfect correlate of non-heterosexual orientation. Here we explored intrasexual variability in psychophysical olfactory performance in a sample of 156 individuals (83 non-heterosexual) and found the lowest odor identification scores in heterosexual men. However, when childhood gender nonconformity was entered in the model along with sexual orientation, better odor identification scores were exhibited by gender-nonconforming men, and greater olfactory sensitivity by gender-conforming women, irrespective of their sexual orientation. Thus, sex-atypicality, but not sexual orientation predicts olfactory performance, and we propose that this might not be limited to olfaction, but represent a more general phenomenon.

  16. Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

    PubMed

    Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

    2010-11-01

    When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Structurally related odorant ligands of the olfactory receptor OR51E2 differentially promote metastasis emergence and tumor growth

    PubMed Central

    Sanz, Guenhaël; Leray, Isabelle; Grébert, Denise; Antoine, Sharmilee; Acquistapace, Adrien; Muscat, Adeline; Boukadiri, Abdelhak; Mir, Lluis M.

    2017-01-01

    Olfactory receptors are G protein-coupled receptors. Some of them are expressed in tumor cells, such as the OR51E2 receptor overexpressed in LNCaP prostate cancer cells. It is considered a prostate tumor marker. We previously demonstrated that this receptor is able to promote LNCaP cell invasiveness in vitro upon stimulation with its odorant agonist β-ionone, leading to increased generation of metastases in vivo. In the present study, we show that even a relatively short exposure to β-ionone is sufficient to promote metastasis emergence. Moreover, α-ionone, considered an OR51E2 antagonist, in fact promotes prostate tumor growth in vivo. The combination of α-ionone with β-ionone triggers a higher increase in the total tumor burden than each molecule alone. To support the in vivo results, we demonstrate in vitro that α-ionone is a real agonist of OR51E2, mainly sustaining LNCaP cell growth, while β-ionone mainly promotes cell invasiveness. So, while structurally close, α-ionone and β-ionone appear to induce different cellular effects, both leading to increased tumor aggressiveness. This behaviour could be explained by a different coupling to downstream effectors, as it has been reported for the so-called biased ligands of other G protein-coupled receptors. PMID:28032594

  18. Evolutionary Genomics of Genes Involved in Olfactory Behavior in the Drosophila melanogaster Species Group

    PubMed Central

    Lavagnino, Nicolás; Serra, François; Arbiza, Leonardo; Dopazo, Hernán; Hasson, Esteban

    2012-01-01

    Previous comparative genomic studies of genes involved in olfactory behavior in Drosophila focused only on particular gene families such as odorant receptor and/or odorant binding proteins. However, olfactory behavior has a complex genetic architecture that is orchestrated by many interacting genes. In this paper, we present a comparative genomic study of olfactory behavior in Drosophila including an extended set of genes known to affect olfactory behavior. We took advantage of the recent burst of whole genome sequences and the development of powerful statistical tools to analyze genomic data and test evolutionary and functional hypotheses of olfactory genes in the six species of the Drosophila melanogaster species group for which whole genome sequences are available. Our study reveals widespread purifying selection and limited incidence of positive selection on olfactory genes. We show that the pace of evolution of olfactory genes is mostly independent of the life cycle stage, and of the number of life cycle stages, in which they participate in olfaction. However, we detected a relationship between evolutionary rates and the position that the gene products occupy in the olfactory system, genes occupying central positions tend to be more constrained than peripheral genes. Finally, we demonstrate that specialization to one host does not seem to be associated with bursts of adaptive evolution in olfactory genes in D. sechellia and D. erecta, the two specialists species analyzed, but rather different lineages have idiosyncratic evolutionary histories in which both historical and ecological factors have been involved. PMID:22346339

  19. Haplotype specific alteration of diabetes MHC risk by olfactory receptor gene polymorphism.

    PubMed

    Jahromi, Mohamed M

    2012-12-01

    Evidence for genes associated with risk for Type 1 diabetes (T1D) in the extended region of the major histocompatibility complex (MHC) genes is accumulating. The aim of this study was to investigate the association pattern of the extended MHC region with T1D susceptibility to identify effects independent of well established DR/DQ genes. A total of 394 Europid families with T1D were genotyped for the single nucleotide polymorphism (SNP) in the olfactory receptor family 14, subfamily J, member 1 (OR14J1) gene, rs9257691, in the MHC telomeric region. The OR provides "an internal depiction of our external world" through the capture of odorant molecules in the main OR system by several large families of G-protein coupled receptors (GPCR). These receptors transduce and chemosignals into the central nervous system (CNS). This SNP was chosen to identify its association with T1D. Interestingly, OR14J1C allele was significantly associated with T1D that seems to go with DRB1*0401, Χ(2)=10.9, p=0.0003. However, by fixing both genes of DR*0401-DQB1*0302, high risk, the association of T1D with OR14J1C still existed, Χ(2)=7.4, p=0.005. The occurrence of association of the OR14J1C allele with T1D patients with DRB1*401/DQB1*0302 is an independent risk for T1D. As an accumulative report suggests the role of OR in the pathogenesis of diabetic microvascular and other diabetic complications, undoubtedly, this haplotype specific alteration of T1D risk is an independent risk for the disease and can address the promising MHC-linked gene other than DR/DQ. Moreover, there is nothing to hinder for that this might be a signal that identifies the role of OR gene in the pathogenesis of T1D in patients who are prone to diabetic complications. Copyright © 2012. Published by Elsevier B.V.

  20. The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

    PubMed

    Courtiol, Emmanuelle; Wilson, Donald A

    2017-01-01

    Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

  1. Brain-derived Neurotrophic Factor Promotes the Migration of Olfactory Ensheathing Cells Through TRPC Channels.

    PubMed

    Wang, Ying; Teng, Hong-Lin; Gao, Yuan; Zhang, Fan; Ding, Yu-Qiang; Huang, Zhi-Hui

    2016-12-01

    Olfactory ensheathing cells (OECs) are a unique type of glial cells with axonal growth-promoting properties in the olfactory system. Organized migration of OECs is essential for neural regeneration and olfactory development. However, the molecular mechanism of OEC migration remains unclear. In the present study, we examined the effects of brain-derived neurotrophic factor (BDNF) on OEC migration. Initially, the "scratch" migration assay, the inverted coverslip and Boyden chamber migration assays showed that BDNF could promote the migration of primary cultured OECs. Furthermore, BDNF gradient attracted the migration of OECs in single-cell migration assays. Mechanistically, TrkB receptor expressed in OECs mediated BDNF-induced OEC migration, and BDNF triggered calcium signals in OECs. Finally, transient receptor potential cation channels (TRPCs) highly expressed in OECs were responsible for BDNF-induced calcium signals, and required for BDNF-induced OEC migration. Taken together, these results demonstrate that BDNF promotes the migration of cultured OECs and an unexpected finding is that TRPCs are required for BDNF-induced OEC migration. GLIA 2016;64:2154-2165. © 2016 Wiley Periodicals, Inc.

  2. IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

    PubMed

    Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

    2017-07-05

    During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Male- and Female-Biased Gene Expression of Olfactory-Related Genes in the Antennae of Asian Corn Borer, Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae)

    PubMed Central

    Zhang, Tiantao; Coates, Brad S.; Ge, Xing; Bai, Shuxiong; He, Kanglai; Wang, Zhenying

    2015-01-01

    The Asian corn borer (ACB), Ostrinia furnacalis (Guenée), is a destructive pest insect of cultivated corn crops, for which antennal-expressed receptors are important to detect olfactory cues for mate attraction and oviposition. Few olfactory related genes were reported in ACB, so we sequenced and characterized the transcriptome of male and female O. furnacalis antennae. Non-normalized male and female O. furnacalis antennal cDNA libraries were sequenced on the Illumina HiSeq 2000 and assembled into a reference transcriptome. Functional gene annotations identified putative olfactory-related genes; 56 odorant receptors (ORs), 23 odorant binding proteins (OBPs), and 10 CSPs. RNA-seq estimates of gene expression respectively showed up- and down-regulation of 79 and 30 genes in female compared to male antennae, which included up-regulation of 8 ORs and 1 PBP gene in male antennae as well as 3 ORs in female antennae. Quantitative real-time RT-PCR analyses validated strong male antennal-biased expression of OfurOR3, 4, 6, 7, 8, 11, 12, 13 and 14 transcripts, whereas OfurOR17 and 18 were specially expressed in female antennae. Sex-biases gene expression described here provides important insight in gene functionalization, and provides candidate genes putatively involved in environmental perception, host plant attraction, and mate recognition. PMID:26062030

  4. An intrinsic vasopressin system in the olfactory bulb is involved in social recognition

    PubMed Central

    Tobin, Vicky A.; Hashimoto, Hirofumi; Wacker, Douglas W.; Takayanagi, Yuki; Langnaese, Kristina; Caquineau, Celine; Noack, Julia; Landgraf, Rainer; Onaka, Tatsushi; Leng, Gareth; Meddle, Simone L.; Engelmann, Mario; Ludwig, Mike

    2010-01-01

    Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain where they play fundamentally important roles in social behaviours1. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders, and obsessive-compulsive disorder, and polymorphisms of the vasopressin V1a receptor have been linked to autism2,3. Here we report that the rat olfactory bulb contains a large population of interneurones which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats, and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurones. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system. PMID:20182426

  5. Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells

    PubMed Central

    Ogura, Tatsuya; Szebenyi, Steven A.; Krosnowski, Kurt; Sathyanesan, Aaron; Jackson, Jacqueline

    2011-01-01

    The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium. PMID:21676931

  6. An olfactory demography of a diverse metropolitan population

    PubMed Central

    2012-01-01

    Background Human perception of the odour environment is highly variable. People vary both in their general olfactory acuity as well as in if and how they perceive specific odours. In recent years, it has been shown that genetic differences contribute to variability in both general olfactory acuity and the perception of specific odours. Odour perception also depends on other factors such as age and gender. Here we investigate the influence of these factors on both general olfactory acuity and on the perception of 66 structurally and perceptually different odours in a diverse subject population. Results We carried out a large human olfactory psychophysics study of 391 adult subjects in metropolitan New York City, an ethnically and culturally diverse North American metropolis. 210 of the subjects were women and the median age was 34.6 years (range 19–75). We recorded ~2,300 data points per subject to obtain a comprehensive perceptual phenotype, comprising multiple perceptual measures of 66 diverse odours. We show that general olfactory acuity correlates with gender, age, race, smoking habits, and body type. Young, female, non-smoking subjects had the highest average olfactory acuity. Deviations from normal body type in either direction were associated with decreased olfactory acuity. Beyond these factors we also show that, surprisingly, there are many odour-specific influences of race, age, and gender on olfactory perception. We show over 100 instances in which the intensity or pleasantness perception of an odour is significantly different between two demographic groups. Conclusions These data provide a comprehensive snapshot of the olfactory sense of a diverse population. Olfactory acuity in the population is most strongly influenced by age, followed by gender. We also show a large number of diverse correlations between demographic factors and the perception of individual odours that may reflect genetic differences as well as different prior experiences with these

  7. Assessment of olfactory threshold in patients undergoing radiotherapy for head and neck malignancies.

    PubMed

    Jalali, Mir Mohammad; Gerami, Hooshang; Rahimi, Abbas; Jafari, Manizheh

    2014-10-01

    Radiotherapy is a common treatment modality for patients with head and neck malignancies. As the nose lies within the field of radiotherapy of the head and neck, the olfactory fibers and olfactory receptors may be affected by radiation. The aim of this study was to evaluate changes in olfactory threshold in patients with head and neck malignancies who have received radiation to the head and neck. The olfactory threshold of patients with head and neck malignancies was assessed prospectively before radiation therapy and serially for up to 6 months after radiotherapy using sniff bottles. In vivo dosimetry was performed using 82 LiF (MCP) chips and a thermoluminescent dosimeter (TLD) system. Sixty-one patients were recruited before radiotherapy was commenced. Seven patients did not return for evaluation after radiation. Fifty-four patients were available for follow-up assessment (28 women, 26 men; age, 22-86 years; median, 49 years). Total radiation dose was 50.1 Gy (range, 30-66 Gy). Mean olfactory threshold scores were found to deteriorate significantly at various timepoints after radiotherapy (11.7 before radiotherapy versus 4.0 at Month 6, general linear model, P<0.0001). With in vivo dosimetry, we found that the median measured dose to the olfactory area was 334 µC. We also identified a cutoff point according to the dose to the olfactory epithelium. Olfactory threshold was significantly decreased 2-6 weeks after initiation of therapy, with cumulative local radiation >135 µC (Mann-Whitney U test, P=0.01). Deterioration in olfactory threshold scores was found at 6 months after initiation of radiation therapy. Provided that these results are reproducible, an evaluation of olfactory functioning in patients with head and neck malignancies using in vivo dosimetry may be useful for determining the optimal dose for patients treated with conformal radiotherapy techniques while avoiding the side effects of radiation.

  8. Neuronal nitric oxide synthase in the olfactory system of an adult teleost fish Oreochromis mossambicus.

    PubMed

    Singru, Praful S; Sakharkar, Amul J; Subhedar, Nishikant

    2003-07-11

    The aim of the present study is to explore the distribution of nitric oxide synthase in the olfactory system of an adult teleost, Oreochromis mossambicus using neuronal nitric oxide synthase (nNOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry methods. Intense nNOS immunoreactivity was noticed in several olfactory receptor neurons (ORNs), in their axonal extensions over the olfactory nerve and in some basal cells of the olfactory epithelium. nNOS containing fascicles of the ORNs enter the bulb from its rostral pole, spread in the olfactory nerve layer in the periphery of the bulb and display massive innervation of the olfactory glomeruli. Unilateral ablation of the olfactory organ resulted in dramatic loss of nNOS immunoreactivity in the olfactory nerve layer of the ipsilateral bulb. In the olfactory bulb of intact fish, some granule cells showed intense immunoreactivity; dendrites arising from the granule cells could be traced to the glomerular layer. Of particular interest is the occurrence of nNOS immunoreactivity in the ganglion cells of the nervus terminalis. nNOS containing fibers were also encountered in the medial olfactory tracts as they extend to the telencephalon. The NADPHd staining generally coincides with that of nNOS suggesting that it may serve as a marker for nNOS in the olfactory system of this fish. However, mismatch was encountered in the case of mitral cells, while all are nNOS-negative, few were NADPHd positive. The present study for the first time revealed the occurrence of nNOS immunoreactivity in the ORNs of an adult vertebrate and suggests a role for nitric oxide in the transduction of odor stimuli, regeneration of olfactory epithelium and processing of olfactory signals.

  9. Presynaptic gain control by endogenous cotransmission of dopamine and GABA in the olfactory bulb.

    PubMed

    Vaaga, Christopher E; Yorgason, Jordan T; Williams, John T; Westbrook, Gary L

    2017-03-01

    In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for decorrelating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry and GABA release as measured by whole cell GABA A receptor currents. Activation of short axon cells reduced the afferent presynaptic release probability via D 2 and GABA B receptor activation, resulting in reduced spiking in both mitral and external tufted cells. Our results suggest that short axon cells influence glomerular activity not only by direct inhibition of external tufted cells but also by inhibition of afferent inputs to external tufted and mitral cells. NEW & NOTEWORTHY Sensory systems, including the olfactory system, encode information across a large dynamic range, making synaptic mechanisms of gain control critical to proper function. Here we demonstrate that a dual-transmitter interneuron in the olfactory bulb controls the gain of intraglomerular afferent input via two distinct mechanisms, presynaptic inhibition as well as inhibition of a principal neuron subtype, and thereby potently controls the synaptic gain of afferent inputs. Copyright © 2017 the American Physiological Society.

  10. 5HTR3A-driven GFP labels immature olfactory sensory neurons.

    PubMed

    Finger, Thomas E; Bartel, Dianna L; Shultz, Nicole; Goodson, Noah B; Greer, Charles A

    2017-05-01

    The ionotropic serotonin receptor, 5-HT 3 , is expressed by many developing neurons within the central nervous system. Since the olfactory epithelium continues to generate new olfactory sensory neurons (OSNs) throughout life, we investigated the possibility that 5-HT 3 is expressed in the adult epithelium. Using a transgenic mouse in which the promoter for the 5-HT 3a subunit drives expression of green fluorescent protein (GFP), we assessed the expression of this marker in the olfactory epithelium of adult mice. Both the native 5-HT 3a mRNA and GFP are expressed within globose basal cells of the olfactory and vomeronasal epithelium in adult mice. Whereas the 5-HT 3a mRNA disappears relatively quickly after final cell division, the GFP label persists for about 5 days, thereby labeling immature OSNs in both the main olfactory system and vomeronasal organ. The GFP-labeled cells include both proliferative globose basal cells as well as immature OSNs exhibiting the hallmarks of ongoing differentiation including GAP43, PGP9.5, but the absence of olfactory marker protein. Some of the GFP-labeled OSNs show characteristics of more mature yet still developing OSNs including the presence of cilia extending from the apical knob and expression of NaV1.5, a component of the transduction cascade. These findings suggest that 5-HT 3a is indicative of a proliferative or developmental state, regardless of age, and that the 5-HT 3A GFP mice may prove useful for future studies of neurogenesis in the olfactory epithelium. J. Comp. Neurol. 525:1743-1755, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Extensive Gains and Losses of Olfactory Receptor Genes in Mammalian Evolution

    PubMed Central

    Niimura, Yoshihito; Nei, Masatoshi

    2007-01-01

    Odor perception in mammals is mediated by a large multigene family of olfactory receptor (OR) genes. The number of OR genes varies extensively among different species of mammals, and most species have a substantial number of pseudogenes. To gain some insight into the evolutionary dynamics of mammalian OR genes, we identified the entire set of OR genes in platypuses, opossums, cows, dogs, rats, and macaques and studied the evolutionary change of the genes together with those of humans and mice. We found that platypuses and primates have <400 functional OR genes while the other species have 800–1,200 functional OR genes. We then estimated the numbers of gains and losses of OR genes for each branch of the phylogenetic tree of mammals. This analysis showed that (i) gene expansion occurred in the placental lineage each time after it diverged from monotremes and from marsupials and (ii) hundreds of gains and losses of OR genes have occurred in an order-specific manner, making the gene repertoires highly variable among different orders. It appears that the number of OR genes is determined primarily by the functional requirement for each species, but once the number reaches the required level, it fluctuates by random duplication and deletion of genes. This fluctuation seems to have been aided by the stochastic nature of OR gene expression. PMID:17684554

  12. Short-term memory in olfactory network dynamics

    NASA Astrophysics Data System (ADS)

    Stopfer, Mark; Laurent, Gilles

    1999-12-01

    Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas.. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.

  13. Neuropeptide Y in the olfactory system, forebrain and pituitary of the teleost, Clarias batrachus.

    PubMed

    Gaikwad, Archana; Biju, K C; Saha, Subhash G; Subhedar, Nishikant

    2004-03-01

    Distribution of neuropeptide Y (NPY)-like immunoreactivity in the forebrain of catfish Clarias batrachus was examined with immunocytochemistry. Conspicuous immunoreactivity was seen in the olfactory receptor neurons (ORNs), their projections in the olfactory nerve, fascicles of the olfactory nerve layer in the periphery of bulb and in the medial olfactory tracts as they extend to the telencephalic lobes. Ablation of the olfactory organ resulted in loss of immunoreactivity in the olfactory nerve layer of the bulb and also in the fascicles of the medial olfactory tracts. This evidence suggests that NPY may serve as a neurotransmitter in the ORNs and convey chemosensory information to the olfactory bulb, and also to the telencephalon over the extrabulbar projections. In addition, network of beaded immunoreactive fibers was noticed throughout the olfactory bulb, which did not respond to ablation experiment. These fibers may represent centrifugal innervation of the bulb. Strong immunoreactivity was encountered in some ganglion cells of nervus terminalis. Immunoreactive fibers and terminal fields were widely distributed in the telencephalon. Several neurons of nucleus entopeduncularis were moderately immunoreactive; and a small population of neurons in nucleus preopticus periventricularis was also labeled. Immunoreactive terminal fields were particularly conspicuous in the preoptic, the tuberal areas, and the periventricular zone around the third ventricle and inferior lobes. NPY immunoreactive cells and fibers were detected in all the lobes of the pituitary gland. Present results describing the localization of NPY in the forebrain of C. batrachus are in concurrence with the pattern of the immunoreactivity encountered in other teleosts. However, NPY in olfactory system of C. batrachus is a novel feature that suggests a role for the peptide in processing of chemosensory information.

  14. Deciphering the function of the CNGB1b subunit in olfactory CNG channels.

    PubMed

    Nache, Vasilica; Wongsamitkul, Nisa; Kusch, Jana; Zimmer, Thomas; Schwede, Frank; Benndorf, Klaus

    2016-07-11

    Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron.

  15. Endogenous GABA and Glutamate Finely Tune the Bursting of Olfactory Bulb External Tufted Cells

    PubMed Central

    Hayar, Abdallah; Ennis, Matthew

    2008-01-01

    In rat olfactory bulb slices, external tufted (ET) cells spontaneously generate spike bursts. Although ET cell bursting is intrinsically generated, its strength and precise timing may be regulated by synaptic input. We tested this hypothesis by analyzing whether the burst properties are modulated by activation of ionotropic γ-aminobutyric acid (GABA) and glutamate receptors. Blocking GABAA receptors increased—whereas blocking ionotropic glutamate receptors decreased—the number of spikes/burst without changing the interburst frequency. The GABAA agonist (isoguvacine, 10 μM) completely inhibited bursting or reduced the number of spikes/burst, suggesting a shunting effect. These findings indicate that the properties of ET cell spontaneous bursting are differentially controlled by GABAergic and glutamatergic fast synaptic transmission. We suggest that ET cell excitatory and inhibitory inputs may be encoded as a change in the pattern of spike bursting in ET cells, which together with mitral/tufted cells constitute the output circuit of the olfactory bulb. PMID:17567771

  16. Endogenous GABA and glutamate finely tune the bursting of olfactory bulb external tufted cells.

    PubMed

    Hayar, Abdallah; Ennis, Matthew

    2007-08-01

    In rat olfactory bulb slices, external tufted (ET) cells spontaneously generate spike bursts. Although ET cell bursting is intrinsically generated, its strength and precise timing may be regulated by synaptic input. We tested this hypothesis by analyzing whether the burst properties are modulated by activation of ionotropic gamma-aminobutyric acid (GABA) and glutamate receptors. Blocking GABA(A) receptors increased--whereas blocking ionotropic glutamate receptors decreased--the number of spikes/burst without changing the interburst frequency. The GABA(A) agonist (isoguvacine, 10 microM) completely inhibited bursting or reduced the number of spikes/burst, suggesting a shunting effect. These findings indicate that the properties of ET cell spontaneous bursting are differentially controlled by GABAergic and glutamatergic fast synaptic transmission. We suggest that ET cell excitatory and inhibitory inputs may be encoded as a change in the pattern of spike bursting in ET cells, which together with mitral/tufted cells constitute the output circuit of the olfactory bulb.

  17. Identification of Putative Chemosensory Receptor Genes from the Athetis dissimilis Antennal Transcriptome

    PubMed Central

    Dong, Junfeng; Song, Yueqin; Li, Wenliang; Shi, Jie; Wang, Zhenying

    2016-01-01

    Olfaction plays a crucial role in insect population survival and reproduction. Identification of the genes associated with the olfactory system, without the doubt will promote studying the insect chemical communication system. In this study, RNA-seq technology was used to sequence the antennae transcriptome of Athetis dissimilis, an emerging crop pest in China with limited genomic information, with the purpose of identifying the gene set involved in olfactory recognition. Analysis of the transcriptome of female and male antennae generated 13.74 Gb clean reads in total from which 98,001 unigenes were assembled, and 25,930 unigenes were annotated. Total of 60 olfactory receptors (ORs), 18 gustatory receptors (GRs), and 12 ionotropic receptors (IRs) were identified by Blast and sequence similarity analyzes. One obligated olfactory receptor co-receptor (Orco) and four conserved sex pheromone receptors (PRs) were annotated in 60 ORs. Among the putative GRs, five genes (AdisGR1, 6, 7, 8 and 94) clustered in the sugar receptor family, and two genes (AdisGR3 and 93) involved in CO2 detection were identified. Finally, AdisIR8a.1 and AdisIR8a.2 co-receptors were identified in the group of candidate IRs. Furthermore, expression levels of these chemosensory receptor genes in female and male antennae were analyzed by mapping the Illumina reads. PMID:26812239

  18. Reference values of olfactory function for Mexico City inhabitants.

    PubMed

    Guarneros, Marco; Hudson, Robyn; López-Palacios, Martha; Drucker-Colín, René

    2015-01-01

    Olfactory testing is useful in the differential diagnosis of age-related pathologies. To provide baseline reference values for clinical use in Mexico City we investigated the relation between olfactory capabilities and the principal population parameters of age, sex, and smoking habits in a large sample of healthy inhabitants. We applied the internationally recognized and commercially available Sniffin' Sticks test battery to 916 men and women from across the adult life span. The Sniffin' Sticks test evaluates three key aspects of olfactory function: 1) ability to detect an odor, 2) to discriminate between odors, and 3) to identify odors. We found a significant decline in olfactory function from the 5th decade of age, and that detection threshold was the most sensitive measure of this. We did not find a significant difference between men and women or between smokers and non-smokers. In confirmation of our previous studies of the negative effect of air pollution on olfactory function, Mexico City inhabitants had poorer overall performance than corresponding subjects previously tested in the neighboring but less polluted Mexican state of Tlaxcala. Although we basically confirm findings on general demographic patterns of olfactory performance from other countries, we also demonstrate the need to take into account local cultural, environmental and demographic factors in the clinical evaluation of olfactory performance of Mexico City inhabitants. The Sniffin' Sticks test battery, with some adjustment of stimuli to correspond to Mexican culture, provides an easily administered means of assessing olfactory health. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  19. Differences in selection drive olfactory receptor genes in different directions in dogs and wolf.

    PubMed

    Chen, Rui; Irwin, David M; Zhang, Ya-Ping

    2012-11-01

    The olfactory receptor (OR) gene family is the largest gene family found in mammalian genomes. It is known to evolve through a birth-and-death process. Here, we characterized the sequences of 16 segregating OR pseudogenes in the samples of the wolf and the Chinese village dog (CVD) and compared them with the sequences from dogs of different breeds. Our results show that the segregating OR pseudogenes in breed dogs are under strong purifying selection, while evolving neutrally in the CVD, and show a more complicated pattern in the wolf. In the wolf, we found a trend to remove deleterious polymorphisms and accumulate nondeleterious polymorphisms. On the basis of protein structure of the ORs, we found that the distribution of different types of polymorphisms (synonymous, nonsynonymous, tolerated, and untolerated) varied greatly between the wolf and the breed dogs. In summary, our results suggest that different forms of selection have acted on the segregating OR pseudogenes in the CVD since domestication, breed dogs after breed formation, and ancestral wolf population, which has driven the evolution of these genes in different directions.

  20. The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map.

    PubMed

    Login, Hande; Håglin, Sofia; Berghard, Anna; Bohm, Staffan

    2015-10-07

    Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DM(high)-VL(low) expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map. The mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the

  1. NADPH-diaphorase activity and NO synthase expression in the olfactory epithelium of the bovine.

    PubMed

    Wenisch, S; Arnhold, S

    2010-06-01

    NADPH-diaphorase (NADPH-d) staining of the bovine olfactory epithelium was compared with the immunohistochemical localization of nitric oxide synthase (NOS), soluble guanylyl cyclase, and cGMP (cyclic guanosine 3',5'-monophosphate). Out of the three isoforms, only the inducible NOS (NOS-II) was found at the epithelial surface correlating with the strong labelling for NADPH-d. In contrast, light diaphorase staining associated with deeper epithelial regions did not coincide with any NOS immunoreactivity. As there is overlapping expression of NOS-II, soluble guanylyl cyclase and cGMP at the luminal surface morphologically occupied by dendritic knobs of olfactory receptor neurons and microvillar endings of supporting cells, the nitric oxide (NO)/cGMP pathway is likely to be involved in modulating the odour signals during olfactory transduction.

  2. Heterogeneity of D2 dopamine receptors in different brain regions.

    PubMed Central

    Leonard, M N; Macey, C A; Strange, P G

    1987-01-01

    The binding of [3H]spiperone has been examined in membranes derived from different regions of bovine brain. In caudate nucleus, nucleus accumbens, olfactory tubercle and putamen binding is to D2 dopamine and 5HT2 serotonin receptors, whereas in cingulate cortex only serotonin 5HT2 receptor binding can be detected. D2 dopamine receptors were examined in detail in caudate nucleus, olfactory tubercle and putamen using [3H]spiperone binding in the presence of 0.3 microM-mianserin (to block 5HT2 serotonin receptors). No evidence for heterogeneity among D2 dopamine receptors either between brain regions or within a brain region was found from the displacements of [3H]spiperone binding by a range of antagonists, including dibenzazepines and substituted benzamides. Regulation of agonist binding by guanine nucleotides did, however, differ between regions. In caudate nucleus a population of agonist binding sites appeared resistant to guanine nucleotide regulation, whereas this was not the case in olfactory tubercle and putamen. PMID:2963621

  3. Immunocytochemistry of the olfactory marker protein.

    PubMed

    Monti-Graziadei, G A; Margolis, F L; Harding, J W; Graziadei, P P

    1977-12-01

    The olfactory marker protein has been localized, by means of immunohistochemical techniques in the primary olfactory neurons of mice. The olfactory marker protein is not present in the staminal cells of the olfactory neuroepithelium, and the protein may be regarded as indicative of the functional stage of the neurons. Our data indicate that the olfactory marker protein is present in the synaptic terminals of the olfactory neurons at the level of the olfactory bulb glomeruli. The postsynaptic profiles of both mitral and periglomerular cells are negative.

  4. Involvement of hormones in olfactory imprinting and homing in chum salmon.

    PubMed

    Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

    2016-02-16

    The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

  5. Accelerated age-related olfactory decline among type 1 Usher patients.

    PubMed

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D

    2016-06-22

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.

  6. Male rats treated with subchronic PCP show intact olfaction and enhanced interest for a social odour in the olfactory habituation/dishabituation test.

    PubMed

    Tarland, Emilia; Brosda, Jan

    2018-06-01

    The olfactory system participates in many sensory processes, and olfactory endophenotypes appear in a variety of neurological disorders such as Alzheimer's and Parkinson's disease, depression and schizophrenia. Social withdrawal is a core negative symptom of schizophrenia and animal models have proven to be invaluable for studying the neurobiological mechanisms and cognitive processes behind the formation of social relationships. The subchronic phencyclidine (PCP) rat model is a validated model for negative symptoms of schizophrenia, such as impaired sociability. However, the complete range of social behaviour and deficits in the model are still not fully understood. Intact rodent olfaction is essential for a wide range of social behaviour and disrupted olfactory function could have severe effects on social communication and recognition. In order to examine the olfactory ability of male rats treated with subchronic PCP, we conducted an olfactory habituation/dishabituation test including both non-social and social odours. The subchronic PCP-treated rats successfully recognized and discriminated among the odours, indicative of intact olfaction. Interestingly, the subchronic PCP-treated rats showed greater interest for a novel social odour compared to the saline-treated rats and the rationale remains to be elucidated. Our data indicate that subchronic PCP treatment does not disrupt olfactory function in male rats. By ruling out impaired olfaction as cause for the poor social interaction performance in subchronic PCP-treated rats, our data supports the use of NMDA receptor antagonists to model the negative symptoms of schizophrenia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Brain activation associated to olfactory conditioned same-sex partner preference in male rats.

    PubMed

    Coria-Avila, Genaro A; Cibrian-Llanderal, Tamara; Díaz-Estrada, Victor X; García, Luis I; Toledo-Cárdenas, Rebeca; Pfaus, James G; Manzo, Jorge

    2018-03-01

    Sexual preferences can be strongly modified by Pavlovian learning. For instance, olfactory conditioned same-sex partner preference can occur when a sexually naïve male cohabits with an scented male during repeated periods under the effects of enhanced D2-type activity. Preference is observed days later via social and sexual behaviors. Herein we explored brain activity related to learned same-sex preference (Fos-Immunoreactivity, IR) following exposure to a conditioned odor paired with same-sex preference. During conditioning trials males received either saline or the D2-type receptor agonist quinpirole (QNP) and cohabitated during 24 h with a stimulus male that bore almond scent on the back as conditioned stimulus. This was repeated every 4 days, for a total of three trials. In a drug-free final test we assessed socio/sexual partner preference between the scented male and a receptive female. The results indicated that QNP-conditioned males developed a same-sex preference observed via contact, time spent, olfactory investigations, and non-contact erections. By contrast, saline-conditioned and intact (non-exposed to conditioning) males expressed an unconditioned preference for the female. Four days later the males were exposed to almond scent and their brains were processed for Fos-IR. Results indicated that the QNP-conditioned group expressed more Fos-IR in the nucleus accumbens (AcbSh), medial preoptic area (MPA), piriform cortex (Pir) and ventromedial nucleus of the hypothalamus (VMH) as compared to saline-conditioned. Intact males expressed the lowest Fos-IR in AcbSh and VMH, but the highest in MPA and Pir. We discuss the role of these areas in the learning process of same-sex partner preferences and olfactory discrimination. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Olfactory Nerve–Evoked, Metabotropic Glutamate Receptor–Mediated Synaptic Responses in Rat Olfactory Bulb Mitral Cells

    PubMed Central

    Ennis, Matthew; Zhu, Mingyan; Heinbockel, Thomas; Hayar, Abdallah

    2008-01-01

    The group I metabotropic glutamate receptor (mGluR) subtype, mGluR1, is highly expressed on the apical dendrites of olfactory bulb mitral cells and thus may be activated by glutamate released from olfactory nerve (ON) terminals. Previous studies have shown that mGluR1 agonists directly excite mitral cells. In the present study, we investigated the involvement of mGluR1 in ON-evoked responses in mitral cells in rat olfactory bulb slices using patch-clamp electrophysiology. In voltage-clamp recordings, the average EPSC evoked by single ON shocks or brief trains of ON stimulation (six pulses at 50 Hz) in normal physiological conditions were not significantly affected by the nonselective mGluR antagonist LY341495 (50–100 μM) or the mGluR1-specific antagonist LY367385 (100 μM); ON-evoked responses were attenuated, however, in a subset (36%) of cells. In the presence of blockers of ionotropic glutamate and GABA receptors, application of the glutamate uptake inhibitors THA (300 μM) and TBOA (100 μM) revealed large-amplitude, long-duration responses to ON stimulation, whereas responses elicited by antidromic activation of mitral/tufted cells were unaffected. Magnitudes of the ON-evoked responses elicited in the presence of THA–TBOA were dependent on stimulation intensity and frequency, and were maximal during high-frequency (50-Hz) bursts of ON spikes, which occur during odor stimulation. ON-evoked responses elicited in the presence of THA–TBOA were significantly reduced or completely blocked by LY341495 or LY367385 (100 μM). These results demonstrate that glutamate transporters tightly regulate access of synaptically evoked glutamate from ON terminals to postsynaptic mGluR1s on mitral cell apical dendrites. Taken together with other findings, the present results suggest that mGluR1s may not play a major role in phasic responses to ON input, but instead may play an important role in shaping slow oscillatory activity in mitral cells and/or activity

  9. Of pheromones and kairomones: what receptors mediate innate emotional responses?

    PubMed

    Fortes-Marco, Lluis; Lanuza, Enrique; Martinez-Garcia, Fernando

    2013-09-01

    Some chemicals elicit innate emotionally laden behavioral responses. Pheromones mediate sexual attraction, parental care or agonistic confrontation, whereas predators' kairomones elicit defensive behaviors in their preys. This essay explores the hypothesis that the detection of these semiochemicals relies on highly specific olfactory and/or vomeronasal receptors. The V1R, V2R, and formyl-peptide vomeronasal receptors bind their ligands in highly specific and sensitive way, thus being good candidates for pheromone- or kairomone-detectors (e.g., secreted and excreted proteins, peptides and lipophilic volatiles). The olfactory epithelium also expresses specific receptors, for example trace amine-associated receptors (TAAR) and guanylyl cyclase receptors (GC-D and other types), some of which bind kairomones and putative pheromones. However, most of the olfactory neurons express canonical olfactory receptors (ORs) that bind many ligands with different affinity, being not suitable for mediating responses to pheromones and kairomones. In this respect, trimethylthiazoline (TMT) is considered a fox-derived kairomone for mice and rats, but it seems to be detected by canonical ORs. Therefore, we have reassessed the kairomonal nature of TMT by analyzing the behavioral responses of outbred (CD1) and inbred mice (C57BL/J6) to TMT. Our results confirm that both mouse strains avoid TMT, which increases immobility in C57BL/J6, but not CD1 mice. However, mice of both strains sniff at TMT throughout the test and show no trace of TMT-induced contextual conditioning (immobility or avoidance). This suggests that TMT is not a kairomone but, similar to a loud noise, in high concentrations it induces aversion and stress as unspecific responses to a strong olfactory stimulation. Copyright © 2013 Wiley Periodicals, Inc.

  10. Zincergic innervation from the anterior olfactory nucleus to the olfactory bulb displays plastic responses after mitral cell loss.

    PubMed

    Airado, Carmen; Gómez, Carmela; Recio, Javier S; Baltanás, Fernando C; Weruaga, Eduardo; Alonso, José R

    2008-12-01

    Zinc ions are selectively accumulated in certain neurons (zinc-enriched neurons). The mouse olfactory bulb is richly innervated by zinc-enriched terminals. Here, the plasticity of the zincergic system was studied in the olfactory bulb of the Purkinje Cell Degeneration mutant mouse, an animal with specific postnatal neurodegeneration of the main projection neurons of the olfactory bulb. The analysis focused particularly on the anterior olfactory nucleus since most centrifugal afferents coming to the olfactory bulb arise from this structure. Zinc-enriched terminals in the olfactory bulb and zinc-enriched somata in the anterior olfactory nucleus were visualized after selenite injections. Immunohistochemistry against the vesicular zinc transporter was also carried out to confirm the distribution pattern of zinc-enriched terminals in the olfactory bulb. The mutant mice showed a clear reorganization of zincergic centrifugal projections from the anterior olfactory nucleus to the olfactory bulb. First, all zincergic contralateral neurons projecting to the olfactory bulb were absent in the mutant mice. Second, a significant increase in the number of stained somata was detected in the ipsilateral anterior olfactory nucleus. Since no noticeable changes were observed in the zinc-enriched terminals in the olfactory bulb, it is conceivable that mitral cell loss could induce a reorganization of zinc-enriched projections coming from the anterior olfactory nucleus, probably directed at balancing the global zincergic centrifugal modulation. These results show that zincergic anterior olfactory nucleus cells projecting to the olfactory bulb undergo plastic changes to adapt to the loss of mitral cells in the olfactory bulb of Purkinje Cell Degeneration mutant mice.

  11. Modulation of the olfactory CNG channel by Ptdlns(3,4,5)P3.

    PubMed

    Zhainazarov, A B; Spehr, M; Wetzel, C H; Hatt, H; Ache, B W

    2004-09-01

    Recent data suggest that the 3-phosphoinositides can modulate cyclic nucleotide signaling in rat olfactory receptor neurons (ORNs). Given the ability of diverse lipids to modulate ion channels, we asked whether phosphatidylinositol 3,4,5-trisphosphate (PIP3) can regulate the olfactory cyclic nucleotide-gated (CNG) channel as a possible mechanism for this modulation. We show that applying PIP3 to the intracellular side of inside-out patches from rat ORNs inhibits activation of the olfactory CNG channel by cAMP. The effect of PIP3 is immediate and partially reversible, and reflects an increase in the EC50 of cAMP, not a reduction in the single-channel current amplitude. The effect of PIP3 is significantly stronger than that of PIP2; other phospholipids tested have no appreciable effect on channel activity. PIP3 similarly inhibits the recombinant heteromeric (A2/A4) and homomeric (A2) olfactory CNG channel expressed in HEK293 cells, suggesting that PIP3 acts directly on the channel. These findings indicate that 3-phosphoinositides can be functionally important regulators of CNG channels.

  12. Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract-piriform cortex synapse

    PubMed Central

    Jones, Paulianda J.; Xiang, Zixiu; Conn, P. Jeffrey

    2008-01-01

    The piriform cortex (PC) is the primary terminal zone of projections from the olfactory bulb, termed the lateral olfactory tract (LOT). The PC plays a critical role in processing of olfactory stimuli and is also a highly seizure prone area thought to be involved in some forms of temporal lobe epilepsy. Pharmacological and immunohistochemical studies provide evidence for the localization of various metabotropic glutamate receptors (GluRs) in the PC. We employed whole cell patch clamp recordings from PC pyramidal cells to determine the roles of group III mGluRs in modulating synaptic transmission at the LOT–PC synapse. The group III mGluR agonist, L-AP4, induced a concentration-dependent inhibition of synaptic transmission at the LOT-PC synapse at concentrations that activate mGluR4 and mGluR8, but not mGluR7 or other mGluR subtypes (EC50 = 473 nM). In addition, the selective mGluR8 agonist, DCPG (300 nM), also suppressed synaptic transmission at the LOT synapse. Furthermore, the inhibitory actions of L-AP4 and Z-cyclopentyl-AP4, a selective mGluR4 agonist, were potentiated by the mGluR4 positive allosteric modulator, PHCCC (30 µM). The high potency of L-AP4, combined with the observed effects of DCPG and PHCCC, suggests that both mGluR4 and mGluR8 play a role in the L-AP4-induced inhibition of synaptic transmission at the LOT-PC synapse. PMID:18625254

  13. Evolution of Olfactory Receptor Genes in Primates Dominated by Birth-and-Death Process

    PubMed Central

    Dong, Dong; He, Guimei; Zhang, Shuyi

    2009-01-01

    Olfactory receptor (OR) is a large family of G protein–coupled receptors that can detect odorant in order to generate the sense of smell. They constitute one of the largest multiple gene families in animals including primates. To better understand the variation in odor perception and evolution of OR genes among primates, we computationally identified OR gene repertoires in orangutans, marmosets, and mouse lemurs and investigated the birth-and-death process of OR genes in the primate lineage. The results showed that 1) all the primate species studied have no more than 400 intact OR genes, fewer than rodents and canine; 2) Despite the similar number of OR genes in the genome, the makeup of the OR gene repertoires between different primate species is quite different as they had undergone dramatic birth-and-death evolution with extensive gene losses in the lineages leading to current species; 3) Apes and Old World monkey (OWM) have similar fraction of pseudogenes, whereas New World monkey (NWM) have fewer pseudogenes. To measure the selective pressure that had affected the OR gene repertoires in primates, we compared the ratio of nonsynonymous with synonymous substitution rates by using 70 one-to-one orthologous quintets among five primate species. We found that OR genes showed relaxed selective constraints in apes (humans, chimpanzees, and orangutans) than in OWMs (macaques) and NWMs (marmosets). We concluded that OR gene repertoires in primates have evolved in such a way to adapt to their respective living environments. Differential selective constraints might play important role in the primate OR gene evolution in each primate species. PMID:20333195

  14. Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

    PubMed

    Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

    2012-08-30

    Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Odorant Inhibition of the Olfactory Cyclic Nucleotide-gated Channel with a Native Molecular Assembly

    PubMed Central

    Chen, Tsung-Yu; Takeuchi, Hiroko; Kurahashi, Takashi

    2006-01-01

    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 Ca2+ 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. PMID:16940558

  16. Molecular Mechanisms of Olfactory Responses to Stimulus Mixtures

    DTIC Science & Technology

    1991-02-26

    demonstrated that the amino acid chemoreceptors in this organism are function- ally coupled to one or more G-proteins (19). Biochemical studies have also shown...Hwang, P.M. and Pevsner, J. (1989) Molecular mechanisms of olfaction. TINS 12, 35-38. 3. Bruch, R.C. (1990) Signal transduction in olfaction and taste ...amino acid olfactory receptor. Comp. Biochem. Physiol. 91B, 535-540. 17. Caprio, J. (1978) Olfaction and taste in the channel catfish: An

  17. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning.

    PubMed

    Munger, Steven D; Leinders-Zufall, Trese; McDougall, Lisa M; Cockerham, Renee E; Schmid, Andreas; Wandernoth, Petra; Wennemuth, Gunther; Biel, Martin; Zufall, Frank; Kelliher, Kevin R

    2010-08-24

    Olfactory signals influence social interactions in a variety of species. In mammals, pheromones and other social cues can promote mating or aggression behaviors; can communicate information about social hierarchies, genetic identity and health status; and can contribute to associative learning. However, the molecular, cellular, and neural mechanisms underlying many olfactory-mediated social interactions remain poorly understood. Here, we report that a specialized olfactory subsystem that includes olfactory sensory neurons (OSNs) expressing the receptor guanylyl cyclase GC-D, the cyclic nucleotide-gated channel subunit CNGA3, and the carbonic anhydrase isoform CAII (GC-D(+) OSNs) is required for the acquisition of socially transmitted food preferences (STFPs) in mice. Using electrophysiological recordings from gene-targeted mice, we show that GC-D(+) OSNs are highly sensitive to the volatile semiochemical carbon disulfide (CS(2)), a component of rodent breath and a known social signal mediating the acquisition of STFPs. Olfactory responses to CS(2) are drastically reduced in mice lacking GC-D, CNGA3, or CAII. Disruption of this sensory transduction cascade also results in a failure to acquire STFPs from either live or surrogate demonstrator mice or to exhibit hippocampal correlates of STFP retrieval. Our findings indicate that GC-D(+) OSNs detect chemosignals that facilitate food-related social interactions. Copyright 2010 Elsevier Ltd. All rights reserved.

  18. Respiratory and olfactory turbinal size in canid and arctoid carnivorans

    PubMed Central

    Green, Patrick A; Valkenburgh, Blaire; Pang, Benison; Bird, Deborah; Rowe, Timothy; Curtis, Abigail

    2012-01-01

    Within the nasal cavity of mammals is a complex scaffold of paper-thin bones that function in respiration and olfaction. Known as turbinals, the bones greatly enlarge the surface area available for conditioning inspired air, reducing water loss, and improving olfaction. Given their functional significance, the relative development of turbinal bones might be expected to differ among species with distinct olfactory, thermoregulatory and/or water conservation requirements. Here we explore the surface area of olfactory and respiratory turbinals relative to latitude and diet in terrestrial Caniformia, a group that includes the canid and arctoid carnivorans (mustelids, ursids, procyonids, mephitids, ailurids). Using high-resolution computed tomography x-ray scans, we estimated respiratory and olfactory turbinal surface area and nasal chamber volume from three-dimensional virtual models of skulls. Across the Caniformia, respiratory surface area scaled isometrically with estimates of body size and there was no significant association with climate, as estimated by latitude. Nevertheless, one-on-one comparisons of sister taxa suggest that arctic species may have expanded respiratory turbinals. Olfactory surface area scaled isometrically among arctoids, but showed positive allometry in canids, reflecting the fact that larger canids, all of which are carnivorous, had relatively greater olfactory surface areas. In addition, among the arctoids, large carnivorous species such as the polar bear (Ursus maritimus) and wolverine (Gulo gulo) also displayed enlarged olfactory turbinals. More omnivorous caniform species that feed on substantial quantities of non-vertebrate foods had less expansive olfactory turbinals. Because large carnivorous species hunt widely dispersed prey, an expanded olfactory turbinal surface area may improve a carnivore's ability to detect prey over great distances using olfactory cues. PMID:23035637

  19. Nasal polyposis (or chronic olfactory rhinitis).

    PubMed

    Jankowski, R; Rumeau, C; Gallet, P; Nguyen, D T

    2018-06-01

    The concept of chronic rhinosinusitis with or without polyps is founded on the structural and functional unicity of the pituitary mucosa and its united response to environmental aggression by allergens, viruses, bacteria, pollution, etc. The present review sets this concept against the evo-devo three-nose theory, in which nasal polyposis is distinguished as specific to the olfactory nose and in particular to the non-olfactory mucosa of the ethmoid, which is considered to be not a sinus but rather the skull-base bone harboring the olfactory mucosa. The evo-devo approach enables simple and precise positive diagnosis of nasal polyposis and its various clinical forms, improves differential diagnosis by distinguishing chronic diseases of the respiratory nose and those of the paranasal sinuses, hypothesizes an autoimmune origin specifically aimed at olfactory system auto-antigens, and supports the surgical concept of nasalization against that of functional sinus and ostiomeatal-complex surgery. The ventilation function of the sinuses seems minor compared to their production, storage and active release of nitric oxide (NO) serving to oxygenate arterial blood in the pulmonary alveoli. This respiratory function of the paranasal sinuses may indeed be their most important. NO trapped in the ethmoidal spaces also accounts for certain radiographic aspects associated with nasal polyposis. Copyright © 2018. Published by Elsevier Masson SAS.

  20. Serotonin modulates the population activity profile of olfactory bulb external tufted cells

    PubMed Central

    Liu, Shaolin; Aungst, Jason L.; Puche, Adam C.

    2012-01-01

    Serotonergic neurons in the raphe nuclei constitute one of the most prominent neuromodulatory systems in the brain. Projections from the dorsal and median raphe nuclei provide dense serotonergic innervation of the glomeruli of olfactory bulb. Odor information is initially processed by glomeruli, thus serotonergic modulation of glomerular circuits impacts all subsequent odor coding in the olfactory system. The present study discloses that serotonin (5-HT) produces excitatory modulation of external tufted (ET) cells, a pivotal neuron in the operation of glomerular circuits. The modulation is due to a transient receptor potential (TRP) channel-mediated inward current induced by activation of 5-HT2A receptors. This current produces membrane depolarization and increased bursting frequency in ET cells. Interestingly, the magnitude of the inward current and increased bursting inversely correlate with ET cell spontaneous (intrinsic) bursting frequency: slower bursting ET cells are more strongly modulated than faster bursting cells. Serotonin thus differentially impacts ET cells such that the mean bursting frequency of the population is increased. This centrifugal modulation could impact odor processing by: 1) increasing ET cell excitatory drive on inhibitory neurons to increase presynaptic inhibition of olfactory sensory inputs and postsynaptic inhibition of mitral/tufted cells; and/or 2) coordinating ET cell bursting with exploratory sniffing frequencies (5–8 Hz) to facilitate odor coding. PMID:22013233

  1. Sex bias in copy number variation of olfactory receptor gene family depends on ethnicity.

    PubMed

    Shadravan, Farideh

    2013-01-01

    Gender plays a pivotal role in the human genetic identity and is also manifested in many genetic disorders particularly mental retardation. In this study its effect on copy number variation (CNV), known to cause genetic disorders was explored. As the olfactory receptor (OR) repertoire comprises the largest human gene family, it was selected for this study, which was carried out within and between three populations, derived from 150 individuals from the 1000 Genome Project. Analysis of 3872 CNVs detected among 791 OR loci, in which 307 loci showed CNV, revealed the following novel findings: Sex bias in CNV was significantly more prevalent in uncommon than common CNV variants of OR pseudogenes, in which the male genome showed more CNVs; and in one-copy number loss compared to complete deletion of OR pseudogenes; both findings implying a more recent evolutionary role for gender. Sex bias in copy number gain was also detected. Another novel finding was that the observed sex bias was largely dependent on ethnicity and was in general absent in East Asians. Using a CNV public database for sick children (International Standard Cytogenomic Array Consortium) the application of these findings for improving clinical molecular diagnostics is discussed by showing an example of sex bias in CNV among kids with autism. Additional clinical relevance is discussed, as the most polymorphic CNV-enriched OR cluster in the human genome, located on chr 15q11.2, is found near the Prader-Willi syndrome/Angelman syndrome bi-directionally imprinted region associated with two well-known mental retardation syndromes. As olfaction represents the primitive cognition in most mammals, arguably in competition with the development of a larger brain, the extensive retention of OR pseudogenes in females of this study, might point to a parent-of-origin indirect regulatory role for OR pseudogenes in the embryonic development of human brain. Thus any perturbation in the temporal regulation of olfactory

  2. Artificial Induction of Associative Olfactory Memory by Optogenetic and Thermogenetic Activation of Olfactory Sensory Neurons and Octopaminergic Neurons in Drosophila Larvae

    PubMed Central

    Honda, Takato; Lee, Chi-Yu; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2016-01-01

    The larval brain of Drosophila melanogaster provides an excellent system for the study of the neurocircuitry mechanism of memory. Recent development of neurogenetic techniques in fruit flies enables manipulations of neuronal activities in freely behaving animals. This protocol describes detailed steps for artificial induction of olfactory associative memory in Drosophila larvae. In this protocol, the natural reward signal is substituted by thermogenetic activation of octopaminergic neurons in the brain. In parallel, the odor signal is substituted by optogenetic activation of a specific class of olfactory receptor neurons. Association of reward and odor stimuli is achieved with the concomitant application of blue light and heat that leads to activation of both sets of neurons in living transgenic larvae. Given its operational simplicity and robustness, this method could be utilized to further our knowledge on the neurocircuitry mechanism of memory in the fly brain. PMID:27445732

  3. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  4. Farnesol-Detecting Olfactory Neurons in Drosophila

    PubMed Central

    Ronderos, David S.; Lin, Chun-Chieh; Potter, Christopher J.

    2014-01-01

    We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical “empty basiconic neuron” system. PMID:24623773

  5. Gray Matter Volume Reduction of Olfactory Cortices in Patients With Idiopathic Olfactory Loss

    PubMed Central

    Yao, Linyin; Pinto, Jayant Marian; Yi, Xiaoli; Li, Li; Peng, Peng

    2014-01-01

    Idiopathic olfactory loss (IOL) is a common olfactory disorder. Little is known about the pathophysiology of this disease. Previous studies demonstrated decreased olfactory bulb (OB) volume in IOL patients when compared with controls. The aim of our study was to investigate structural brain alterations in areas beyond the OB. We acquired T1-weighted magnetic resonance images from 16 patients with IOL and from 16 age- and sex-matched controls on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. Psychophysical testing confirmed that patients had higher scores for Toyota and Takagi olfactometer and lower scores for Sniffin’ Sticks olfactory test than controls (t = 46.9, P < 0.001 and t = 21.4, P < 0.001, respectively), consistent with olfactory dysfunction. There was a significant negative correlation between the 2 olfactory tests (r = −0.6, P = 0.01). In a volume of interest analysis including primary and secondary olfactory areas, we found patients with IOL to exhibit gray matter volume loss in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal cortex, and the piriform cortex. The present study indicates that changes in the central brain structures proximal to the OB occur in IOL. Further investigations of this phenomenon may be helpful to elucidate the etiology of IOL. PMID:25240014

  6. Activation of glial FGFRs is essential in glial migration, proliferation, and survival and in glia-neuron signaling during olfactory system development.

    PubMed

    Gibson, Nicholas J; Tolbert, Leslie P; Oland, Lynne A

    2012-01-01

    Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells.

  7. Respiratory and olfactory turbinal size in canid and arctoid carnivorans.

    PubMed

    Green, Patrick A; Van Valkenburgh, Blaire; Pang, Benison; Bird, Deborah; Rowe, Timothy; Curtis, Abigail

    2012-12-01

    Within the nasal cavity of mammals is a complex scaffold of paper-thin bones that function in respiration and olfaction. Known as turbinals, the bones greatly enlarge the surface area available for conditioning inspired air, reducing water loss, and improving olfaction. Given their functional significance, the relative development of turbinal bones might be expected to differ among species with distinct olfactory, thermoregulatory and/or water conservation requirements. Here we explore the surface area of olfactory and respiratory turbinals relative to latitude and diet in terrestrial Caniformia, a group that includes the canid and arctoid carnivorans (mustelids, ursids, procyonids, mephitids, ailurids). Using high-resolution computed tomography x-ray scans, we estimated respiratory and olfactory turbinal surface area and nasal chamber volume from three-dimensional virtual models of skulls. Across the Caniformia, respiratory surface area scaled isometrically with estimates of body size and there was no significant association with climate, as estimated by latitude. Nevertheless, one-on-one comparisons of sister taxa suggest that arctic species may have expanded respiratory turbinals. Olfactory surface area scaled isometrically among arctoids, but showed positive allometry in canids, reflecting the fact that larger canids, all of which are carnivorous, had relatively greater olfactory surface areas. In addition, among the arctoids, large carnivorous species such as the polar bear (Ursus maritimus) and wolverine (Gulo gulo) also displayed enlarged olfactory turbinals. More omnivorous caniform species that feed on substantial quantities of non-vertebrate foods had less expansive olfactory turbinals. Because large carnivorous species hunt widely dispersed prey, an expanded olfactory turbinal surface area may improve a carnivore's ability to detect prey over great distances using olfactory cues. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  8. Structural differences in the drone olfactory system of two phylogenetically distant Apis species, A. florea and A. mellifera

    NASA Astrophysics Data System (ADS)

    Brockmann, Axel; Brückner, Dorothea

    2001-01-01

    Male insects that are attracted by sex pheromones to find their female mates over long distances have specialized olfactory subsystems. Morphologically, these subsystems are characterized by a large number of receptor neurons sensitive to components of the female's pheromones and hypertrophied glomerular subunits ('macroglomeruli' or 'macroglomerular complexes') in the antennal lobes, in which the axons of the receptor neurons converge. The olfactory subsystems are adapted for an increased sensitivity to perceive minute amounts of pheromones. In Apis mellifera, drones have 18,600 olfactory poreplate sensilla per antenna, each equipped with receptor neurons sensitive to the queen's sex pheromone, and four voluminous macroglomeruli (MG1-MG4) in the antennal lobes. In contrast, we show that drones of the phylogenetically distant species, Apis florea, have only 1,200 poreplate sensilla per antenna and only two macroglomeruli in their antennal lobes. These macroglomeruli are homologous in anatomical position to the two most prominent macroglomeruli in A. mellifera, the MG1 and MG2, but they are much smaller in size. The morphological and anatomical differences described here suggest major modifications in the sex-pheromone processing subsystem of both species: (1) less pheromone sensitivity in A. florea and (2) a more complex sex-pheromone processing and thus a more complex sex-pheromone communication in A. mellifera.

  9. Ecological adaptation determines functional mammalian olfactory subgenomes

    PubMed Central

    Hayden, Sara; Bekaert, Michaël; Crider, Tess A.; Mariani, Stefano; Murphy, William J.; Teeling, Emma C.

    2010-01-01

    The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families. PMID:19952139

  10. Identification and expression analysis of an olfactory receptor gene family in green plant bug Apolygus lucorum (Meyer-Dür)

    PubMed Central

    An, Xing-Kui; Sun, Liang; Liu, Hang-Wei; Liu, Dan-Feng; Ding, Yu-Xiao; Li, Le-Mei; Zhang, Yong-Jun; Guo, Yu-Yuan

    2016-01-01

    Olfactory receptors are believed to play a central role in insects host-seeking, mating, and ovipositing. On the basis of male and female antennal transcriptome of adult Apolygus lucorum, a total of 110 candidate A. lucorum odorant receptors (AlucOR) were identified in this study including five previously annotated AlucORs. All the sequences were validated by cloning and sequencing. Tissue expression profiles analysis by RT-PCR indicated most AlucORs were antennal highly expressed genes. The qPCR measurements further revealed 40 AlucORs were significantly higher in the antennae. One AlucOR was primarily expressed in the female antennae, while nine AlucORs exhibited male-biased expression patterns. Additionally, both the RPKM value and RT-qPCR analysis showed AlucOR83 and AlucOR21 were much higher abundant in male antennae than in female antennae, suggesting their different roles in chemoreception of gender. Phylogenetic analysis of ORs from several Hemipteran species demonstrated that most AlucORs had orthologous genes, and five AlucOR-specific clades were defined. In addition, a sub-clade of potential male-based sex pheromone receptors were also identified in the phylogenetic tree of AlucORs. Our results will facilitate the functional studies of AlucORs, and thereby provide a foundation for novel pest management approaches based on these genes. PMID:27892490

  11. Analysis of the Antennal Transcriptome and Insights into Olfactory Genes in Hyphantria cunea (Drury)

    PubMed Central

    Wang, Tian-Tian; Zhang, Jing; Sun, Long; Yang, Yun-Qiu; Huang, Chang-Chun; Jiang, Li-Ya; Ding, De-Gui

    2016-01-01

    Hyphantria cunea (Drury) (Lepidoptera: Arctiidae) is an invasive insect pest which, in China, causes unprecedented damage and economic losses due to its extreme fecundity and wide host range, including forest and shade trees, and even crops. Compared to the better known lepidopteran species which use Type-I pheromones, little is known at the molecular level about the olfactory mechanisms of host location and mate choice in H. cunea, a species using Type-II lepidopteran pheromones. In the present study, the H. cunea antennal transcriptome was constructed by Illumina Hiseq 2500TM sequencing, with the aim of discovering olfaction-related genes. We obtained 64,020,776 clean reads, and 59,243 unigenes from the analysis of the transcriptome, and the putative gene functions were annotated using gene ontology (GO) annotation. We further identified 124 putative chemosensory unigenes based on homology searches and phylogenetic analysis, including 30 odorant binding proteins (OBPs), 17 chemosensory proteins (CSPs), 52 odorant receptors (ORs), 14 ionotropic receptors (IRs), nine gustatory receptors (GRs) and two sensory neuron membrane proteins (SNMPs). We also found many conserved motif patterns of OBPs and CSPs using a MEME system. Moreover, we systematically analyzed expression patterns of OBPs and CSPs based on reverse transcription PCR and quantitative real time PCR (RT-qPCR) with RNA extracted from different tissues and life stages of both sexes in H. cunea. The antennae-biased expression may provide a deeper further understanding of olfactory processing in H. cunea. The first ever identification of olfactory genes in H. cunea may provide new leads for control of this major pest. PMID:27741298

  12. Analysis of the Antennal Transcriptome and Insights into Olfactory Genes in Hyphantria cunea (Drury).

    PubMed

    Zhang, Long-Wa; Kang, Ke; Jiang, Shi-Chang; Zhang, Ya-Nan; Wang, Tian-Tian; Zhang, Jing; Sun, Long; Yang, Yun-Qiu; Huang, Chang-Chun; Jiang, Li-Ya; Ding, De-Gui

    2016-01-01

    Hyphantria cunea (Drury) (Lepidoptera: Arctiidae) is an invasive insect pest which, in China, causes unprecedented damage and economic losses due to its extreme fecundity and wide host range, including forest and shade trees, and even crops. Compared to the better known lepidopteran species which use Type-I pheromones, little is known at the molecular level about the olfactory mechanisms of host location and mate choice in H. cunea, a species using Type-II lepidopteran pheromones. In the present study, the H. cunea antennal transcriptome was constructed by Illumina Hiseq 2500TM sequencing, with the aim of discovering olfaction-related genes. We obtained 64,020,776 clean reads, and 59,243 unigenes from the analysis of the transcriptome, and the putative gene functions were annotated using gene ontology (GO) annotation. We further identified 124 putative chemosensory unigenes based on homology searches and phylogenetic analysis, including 30 odorant binding proteins (OBPs), 17 chemosensory proteins (CSPs), 52 odorant receptors (ORs), 14 ionotropic receptors (IRs), nine gustatory receptors (GRs) and two sensory neuron membrane proteins (SNMPs). We also found many conserved motif patterns of OBPs and CSPs using a MEME system. Moreover, we systematically analyzed expression patterns of OBPs and CSPs based on reverse transcription PCR and quantitative real time PCR (RT-qPCR) with RNA extracted from different tissues and life stages of both sexes in H. cunea. The antennae-biased expression may provide a deeper further understanding of olfactory processing in H. cunea. The first ever identification of olfactory genes in H. cunea may provide new leads for control of this major pest.

  13. Histological and Lectin Histochemical Studies on the Olfactory and Respiratory Mucosae of the Sheep

    PubMed Central

    IBRAHIM, Dalia; NAKAMUTA, Nobuaki; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; TANIGUCHI, Kazuyuki

    2013-01-01

    ABSTRACT The olfactory and respiratory mucosae of the Corriedale sheep were examined using lectin histochemistry in order to clarify the histochemical and glycohistochemical differences between these two tissues. The olfactory epithelium was stained with 13 lectins out of 21 lectins examined, while the respiratory epithelium was positive to 16 lectins. The free border of both of the olfactory and respiratory epithelia was stained with 12 lectins: Wheat germ agglutinin (WGA), succinylated-wheat germ agglutinin (s-WGA), Lycopersicon esculentum lectin (LEL), Solanum tuberosum lectin (STL), Datura stramonium lectin (DSL), Soybean agglutinin (SBA), Bandeiraea simplicifolia lectin-I (BSL-I), Ricinus communis agglutinin-I (RCA-120), Erythrina cristagalli lectin (ECL), Concanavalin A (Con A), Phaseolus vulgaris agglutinin-E (PHA-E) and Phaseolus vulgaris agglutinin-L (PHA-L). The associated glands of the olfactory mucosa, Bowman’s glands, were stained with 13 lectins. While both the goblet cells and mucous nasal glands were stained with 8 lectins; five of them (WGA, s-WGA, STL, Vicia villosa agglutinin (VVA) and ECL) were mutually positive among the Bowman’s glands, mucous nasal glands and the goblet cells. These findings indicate that the glycohistochemical characteristics of the free borders of both olfactory and respiratory epithelia are similar to each other, suggesting that secretions from the Bowman’s glands and those of the goblet cells and mucous nasal glands are partially exchanged between the surface of two epithelia to contribute the functions of the respiratory epithelium and the olfactory receptor cells, respectively. PMID:24200894

  14. Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

    PubMed Central

    Chelminski, Yan; Magnan, Christophe; Luquet, Serge H.; Everard, Amandine; Meunier, Nicolas; Gurden, Hirac; Martin, Claire

    2017-01-01

    Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning. PMID:28154537

  15. Integration of bio-inspired, control-based visual and olfactory data for the detection of an elusive target

    NASA Astrophysics Data System (ADS)

    Duong, Tuan A.; Duong, Nghi; Le, Duong

    2017-01-01

    In this paper, we present an integration technique using a bio-inspired, control-based visual and olfactory receptor system to search for elusive targets in practical environments where the targets cannot be seen obviously by either sensory data. Bio-inspired Visual System is based on a modeling of extended visual pathway which consists of saccadic eye movements and visual pathway (vertebrate retina, lateral geniculate nucleus and visual cortex) to enable powerful target detections of noisy, partial, incomplete visual data. Olfactory receptor algorithm, namely spatial invariant independent component analysis, that was developed based on data of old factory receptor-electronic nose (enose) of Caltech, is adopted to enable the odorant target detection in an unknown environment. The integration of two systems is a vital approach and sets up a cornerstone for effective and low-cost of miniaturized UAVs or fly robots for future DOD and NASA missions, as well as for security systems in Internet of Things environments.

  16. Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

    PubMed Central

    Amchova, Petra; Kucerova, Jana; Giugliano, Valentina; Babinska, Zuzana; Zanda, Mary T.; Scherma, Maria; Dusek, Ladislav; Fadda, Paola; Micale, Vincenzo; Sulcova, Alexandra; Fratta, Walter; Fattore, Liana

    2013-01-01

    Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5–10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats. PMID:24688470

  17. Postnatal Experience Modulates Functional Properties of Mouse Olfactory Sensory Neurons

    PubMed Central

    He, Jiwei; Tian, Huikai; Lee, Anderson C.; Ma, Minghong

    2012-01-01

    Early experience considerably modulates the organization and function of all sensory systems. In the mammalian olfactory system, deprivation of the sensory inputs via neonatal, unilateral naris closure has been shown to induce structural, molecular, and functional changes from the olfactory epithelium to the olfactory bulb and cortex. However, it remains unknown how early experience shapes functional properties of individual olfactory sensory neurons (OSNs), the primary odor detectors in the nose. To address this question, we examined odorant response properties of mouse OSNs in both the closed and open nostril after four weeks of unilateral naris closure with age-matched untreated animals as control. Using patch-clamp technique on genetically-tagged OSNs with defined odorant receptors (ORs), we found that sensory deprivation increased the sensitivity of MOR23 neurons in the closed side while overexposure caused the opposite effect in the open side. We next analyzed the response properties including rise time, decay time, and adaptation induced by repeated stimulation in MOR23 and M71 neurons. Even though these two types of neurons showed distinct properties in dynamic range and response kinetics, sensory deprivation significantly slowed down the decay phase of odorant-induced transduction events in both types. Using western blotting and antibody staining, we confirmed upregulation of several signaling proteins in the closed side as compared with the open side. This study suggests that early experience modulates functional properties of OSNs, probably via modifying the signal transduction cascade. PMID:22703547

  18. Odourant dominance in olfactory mixture processing: what makes a strong odourant?

    PubMed Central

    Schubert, Marco; Sandoz, Jean-Christophe; Galizia, Giovanni; Giurfa, Martin

    2015-01-01

    The question of how animals process stimulus mixtures remains controversial as opposing views propose that mixtures are processed analytically, as the sum of their elements, or holistically, as unique entities different from their elements. Overshadowing is a widespread phenomenon that can help decide between these alternatives. In overshadowing, an individual trained with a binary mixture learns one element better at the expense of the other. Although element salience (learning success) has been suggested as a main explanation for overshadowing, the mechanisms underlying this phenomenon remain unclear. We studied olfactory overshadowing in honeybees to uncover the mechanisms underlying olfactory-mixture processing. We provide, to our knowledge, the most comprehensive dataset on overshadowing to date based on 90 experimental groups involving more than 2700 bees trained either with six odourants or with their resulting 15 binary mixtures. We found that bees process olfactory mixtures analytically and that salience alone cannot predict overshadowing. After normalizing learning success, we found that an unexpected feature, the generalization profile of an odourant, was determinant for overshadowing. Odourants that induced less generalization enhanced their distinctiveness and became dominant in the mixture. Our study thus uncovers features that determine odourant dominance within olfactory mixtures and allows the referring of this phenomenon to differences in neural activity both at the receptor and the central level in the insect nervous system. PMID:25652840

  19. Acetylcholine and Olfactory Perceptual Learning

    ERIC Educational Resources Information Center

    Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

    2004-01-01

    Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform…

  20. Intrinsic and Extrinsic Neuromodulation of Olfactory Processing

    PubMed Central

    Lizbinski, Kristyn M.; Dacks, Andrew M.

    2018-01-01

    Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a “memory” by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform. PMID:29375314

  1. Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.

    PubMed

    Lizbinski, Kristyn M; Dacks, Andrew M

    2017-01-01

    Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

  2. Topological and Functional Characterization of an Insect Gustatory Receptor

    PubMed Central

    Zhang, Hui-Jie; Anderson, Alisha R.; Trowell, Stephen C.; Luo, A-Rong; Xiang, Zhong-Huai; Xia, Qing-You

    2011-01-01

    Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol. PMID:21912618

  3. Non-NMDA receptor antagonist-induced drinking in rat

    NASA Technical Reports Server (NTRS)

    Xu, Z.; Johnson, A. K.

    1998-01-01

    Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

  4. Identification of second messenger mediating signal transduction in the olfactory receptor cell.

    PubMed

    Takeuchi, Hiroko; Kurahashi, Takashi

    2003-11-01

    One of the biggest controversial issues in the research of olfaction has been the mechanism underlying response generation to odorants that have been shown to fail to produce cAMP when tested by biochemical assays with olfactory ciliary preparations. Such observations are actually the original source proposing a possibility for the presence of multiple and parallel transduction pathways. In this study the activity of transduction channels in the olfactory cilia was recorded in cells that retained their abilities of responding to odorants that have been reported to produce InsP3 (instead of producing cAMP, and therefore tentatively termed "InsP3 odorants"). At the same time, the cytoplasmic cNMP concentration ([cNMP]i) was manipulated through the photolysis of caged compounds to examine their real-time interactions with odorant responses. Properties of responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each other in their unique characteristics. Reversal potentials of currents were 2 mV for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and voltage (I-V) relations showed slight outward rectification. Both responses showed voltage-dependent adaptation when examined with double pulse protocols. When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied alternatively, responses expressed cross-adaptation with each other. Furthermore, both responses were additive in a manner as predicted quantitatively by the theory that signal transduction is mediated by the increase in cytoplasmic cAMP. With InsP3 odorants, actually, remarkable responses could be detected in a small fraction of cells ( approximately 2%), explaining the observation for a small production of cAMP in ciliary preparations obtained from the entire epithelium. The data will provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

  5. Activation of Glial FGFRs Is Essential in Glial Migration, Proliferation, and Survival and in Glia-Neuron Signaling during Olfactory System Development

    PubMed Central

    Gibson, Nicholas J.; Tolbert, Leslie P.; Oland, Lynne A.

    2012-01-01

    Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells. PMID:22493675

  6. Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xie, Fang; Fang, Cheng; School of Public Health, State University of New York at Albany, NY 12201

    We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasalmore » cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels.

  7. Immunohistochemical characterization of human olfactory tissue

    PubMed Central

    Holbrook, Eric H.; Wu, Enming; Curry, William T.; Lin, Derrick T.; Schwob, James E.

    2011-01-01

    Objectives/Hypothesis The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction. Study Design An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies. Methods Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma. Results Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of the esthesioneuroblastoma. Conclusion The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurological disease. The similarities in human vs. rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology. PMID:21792956

  8. Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.

    PubMed

    Tong, Jia; Okutani, Fumino; Murata, Yoshihiro; Taniguchi, Mutsuo; Namba, Toshiharu; Wang, Yu-Jie; Kaba, Hideto

    2017-03-06

    Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Olfactory Cleft Endoscopy Scale correlates with olfactory metrics in patients with chronic rhinosinusitis

    PubMed Central

    Soler, Zachary M.; Hyer, J. Madison; Karnezis, Tom T.; Schlosser, Rodney J.

    2015-01-01

    Introduction Olfactory loss affects a majority of patients with chronic rhinosinusitis (CRS). Traditional objective measures of disease severity, including endoscopy scales, focus upon the paranasal sinuses and often have weak correlation to olfaction. Methods Adults with CRS were prospectively evaluated by blinded reviewers with a novel Olfactory Cleft Endoscopy Scale (OCES) that evaluated discharge, polyps, edema, crusting and scarring of the olfactory cleft. Objective olfactory function was assessed using “Sniffin’ Sticks testing, including composite threshold-discrimination-identification (TDI) scores. Olfactory-specific quality-of-life was evaluated using the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS). Inter- and intra-rater reliability was assessed among 3 reviewers for OCES grading. Multivariate linear regression was then used to test associations between OCES scores and measures of olfaction, controlling for potential confounding factors. Results The OCES score was evaluated in 38 patients and had a high overall reliability (ICC=0.92; 95% CI: 0.91–0.96). The OCES significantly correlated with objective olfaction as measured by TDI score (p<0.001), with TDI score falling by 1.13 points for every 1 point increase in OCES score. Similar significant associations were found for threshold, discrimination, and identification scores (p<0.003 for all) after controlling for age, gender, race, and reviewer/review. The OCES was also highly associated with patient-reported QOD-NS scores (p=0.009). Conclusion A novel olfactory cleft endoscopy scale shows high reliability and correlates with both objective and patient-reported olfaction in patients with CRS. Further studies to determine prognostic value and responsiveness to change are warranted. PMID:26718315

  10. Response Times to Gustatory–Olfactory Flavor Mixtures: Role of Congruence

    PubMed Central

    Shepard, Timothy G.; Veldhuizen, Maria G.

    2015-01-01

    A mixture of perceptually congruent gustatory and olfactory flavorants (sucrose and citral) was previously shown to be detected faster than predicted by a model of probability summation that assumes stochastically independent processing of the individual gustatory and olfactory signals. This outcome suggests substantial integration of the signals. Does substantial integration also characterize responses to mixtures of incongruent flavorants? Here, we report simple response times (RTs) to detect brief pulses of 3 possible flavorants: monosodium glutamate, MSG (gustatory: “umami” quality), citral (olfactory: citrus quality), and a mixture of MSG and citral (gustatory–olfactory). Each stimulus (and, on a fraction of trials, water) was presented orally through a computer-operated, automated flow system, and subjects were instructed to press a button as soon as they detected any of the 3 non-water stimuli. Unlike responses previously found to the congruent mixture of sucrose and citral, responses here to the incongruent mixture of MSG and citral took significantly longer (RTs were greater) and showed lower detection rates than the values predicted by probability summation. This outcome suggests that the integration of gustatory and olfactory flavor signals is less extensive when the component flavors are perceptually incongruent rather than congruent, perhaps because incongruent flavors are less familiar. PMID:26304508

  11. Cortical Plasticity and Olfactory Function in Early Blindness

    PubMed Central

    Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

  12. Identification of a Novel Gnao-Mediated Alternate Olfactory Signaling Pathway in Murine OSNs.

    PubMed

    Scholz, Paul; Mohrhardt, Julia; Jansen, Fabian; Kalbe, Benjamin; Haering, Claudia; Klasen, Katharina; Hatt, Hanns; Osterloh, Sabrina

    2016-01-01

    It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl(-) efflux; however, the activation of adenylyl cyclase III (ACIII), the recruitment of Ca(2+) from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling) are not involved. Furthermore, we demonstrated that our newly identified pathway coexists with the canonical olfactory cAMP pathway in the same OSN and can be triggered by the same OR in a ligand-selective manner. We suggest that this pathway might reflect a mechanism for odor recognition predominantly used in early developmental stages before olfactory cAMP signaling is fully developed. Taken together, our findings support the existence of at least one odor-induced alternate signal transduction pathway in native OSNs mediated by Olfr73 in a ligand-selective manner.

  13. Molecular and Cellular Designs of Insect Taste Receptor System

    PubMed Central

    Isono, Kunio; Morita, Hiromi

    2010-01-01

    The insect gustatory receptors (GRs) are members of a large G-protein coupled receptor family distantly related to the insect olfactory receptors. They are phylogenetically different from taste receptors of most other animals. GRs are often coexpressed with other GRs in single receptor neurons. Taste receptors other than GRs are also expressed in some neurons. Recent molecular studies in the fruitfly Drosophila revealed that the insect taste receptor system not only covers a wide ligand spectrum of sugars, bitter substances or salts that are common to mammals but also includes reception of pheromone and somatosensory stimulants. However, the central mechanism to perceive and discriminate taste information is not yet elucidated. Analysis of the primary projection of taste neurons to the brain shows that the projection profiles depend basically on the peripheral locations of the neurons as well as the GRs that they express. These results suggest that both peripheral and central design principles of insect taste perception are different from those of olfactory perception. PMID:20617187

  14. The Evolution of Olfactory Gene Families in Drosophila and the Genomic Basis of chemical-Ecological Adaptation in Drosophila suzukii.

    PubMed

    Ramasamy, Sukanya; Ometto, Lino; Crava, Cristina M; Revadi, Santosh; Kaur, Rupinder; Horner, David S; Pisani, Davide; Dekker, Teun; Anfora, Gianfranco; Rota-Stabelli, Omar

    2016-08-16

    How the evolution of olfactory genes correlates with adaption to new ecological niches is still a debated topic. We explored this issue in Drosophila suzukii, an emerging model that reproduces on fresh fruit rather than in fermenting substrates like most other Drosophila We first annotated the repertoire of odorant receptors (ORs), odorant binding proteins (OBPs), and antennal ionotropic receptors (aIRs) in the genomes of two strains of D. suzukii and of its close relative Drosophila biarmipes We then analyzed these genes on the phylogeny of 14 Drosophila species: whereas ORs and OBPs are characterized by higher turnover rates in some lineages including D. suzukii, aIRs are conserved throughout the genus. Drosophila suzukii is further characterized by a non-random distribution of OR turnover on the gene phylogeny, consistent with a change in selective pressures. In D. suzukii, we found duplications and signs of positive selection in ORs with affinity for short-chain esters, and loss of function of ORs with affinity for volatiles produced during fermentation. These receptors-Or85a and Or22a-are characterized by divergent alleles in the European and American genomes, and we hypothesize that they may have been replaced by some of the duplicated ORs in corresponding neurons, a hypothesis reciprocally confirmed by electrophysiological recordings. Our study quantifies the evolution of olfactory genes in Drosophila and reveals an array of genomic events that can be associated with the ecological adaptations of D. suzukii. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Olfactory cortical adaptation facilitates detection of odors against background.

    PubMed

    Kadohisa, Mikiko; Wilson, Donald A

    2006-03-01

    Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.

  16. Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish.

    PubMed

    Harden, Maegan V; Newton, Lucy A; Lloyd, Russell C; Whitlock, Kathleen E

    2006-11-01

    Odors experienced as juveniles can have significant effects on the behavior of mature organisms. A dramatic example of this occurs in salmon, where the odors experienced by developing fish determine the river to which they return as adults. Further examples of olfactory memories are found in many animals including vertebrates and invertebrates. Yet, the cellular and molecular bases underlying the formation of olfactory memory are poorly understood. We have devised a series of experiments to determine whether zebrafish can form olfactory memories much like those observed in salmonids. Here we show for the first time that zebrafish form and retain olfactory memories of an artificial odorant, phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate that exposure to PEA results in changes in gene expression within the olfactory sensory system. These changes are evident by in situ hybridization in the olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA. This increase is evident at 2-3 days postfertilization and is maintained in the adult animals. We propose that the changes in otx2 gene expression are manifest as an increase in the number of neuronal precursors in the cells olfactory epithelium of the odor-exposed fish. Thus, our results reveal a role for the environment in controlling gene expression in the developing peripheral nervous system. Copyright 2006 Wiley Periodicals, Inc.

  17. Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

    PubMed

    Fornai, F; Bassi, L; Gesi, M; Giorgi, F S; Guerrini, R; Bonaccorsi, I; Alessandrì, M G

    2000-01-01

    Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli

  18. Olfactory Functioning in First-Episode Psychosis.

    PubMed

    Kamath, Vidyulata; Lasutschinkow, Patricia; Ishizuka, Koko; Sawa, Akira

    2018-04-06

    Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are

  19. Odor Coding by a Mammalian Receptor Repertoire

    PubMed Central

    Saito, Harumi; Chi, Qiuyi; Zhuang, Hanyi; Matsunami, Hiro; Mainland, Joel D.

    2009-01-01

    Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of over 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and unraveling mammalian odor coding. PMID:19261596

  20. Ca2+ ion permeability properties of (R,S) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in isolated interneurons from the olfactory bulb of the rat.

    PubMed

    Jardemark, K; Nilsson, M; Muyderman, H; Jacobson, I

    1997-02-01

    The aim of the study was to investigate the divalent cation permeability of native alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors expressed in interneurons of the olfactory bulb. Kainic acid (KA) was used as agonist to activate AMPA-receptor-mediated currents, which were recorded with the use of the patch-clamp technique. In interneurons acutely isolated from the olfactory bulb, the current responses to KA showed linear/outwardly rectifying current-voltage (I-V) relationships with a positive average reversal potential of +7 mV in normal external medium (1 mM Ca2+, 1 mM Mg2+). Raising the external Ca2+ concentration to 10 mM suppressed the amplitude, whereas omission of Ca2+ enhanced the amplitude of the current. Spectral analysis of the increase in current variance produced by KA indicated that the decreased amplitude observed in 10 mM Ca2+ was accompanied by a reduction in the apparent single-channel conductance. Raising the concentration of Mg2+ from 1 to 10 mM had a weak depressant effect on the KA-evoked current amplitude. No shift in the reversal potential was observed when the concentration of Ca2+ or Mg2+ was changed from 1 to 10 mM. Increasing the external medium concentration of Ca2+ to 60 mM not only further depressed the amplitudes of the KA-evoked currents but also gave a pronounced leftward shift in the average reversal potential to -32 +/- 9 (SE) mV (N = 7). For neurons in primary culture, current responses to KA also showed linear/outwardly rectifying I-V relationships with a positive average reversal potential in normal external medium. Substituting N-methylglucamine for Na+ and increasing the Ca2+ concentration to 10 mM gave a leftward shift in the average reversal potential from +9 +/- 3 mV to -47 +/- 4 mV (N = 11) and caused a marked reduction in the amplitude of the KA-evoked currents at negative potentials. The permeability properties of the studied AMPA receptors were well predicted by the Eyring rate model (symmetrical

  1. A Review of Current Neuromorphic Approaches for Vision, Auditory, and Olfactory Sensors.

    PubMed

    Vanarse, Anup; Osseiran, Adam; Rassau, Alexander

    2016-01-01

    Conventional vision, auditory, and olfactory sensors generate large volumes of redundant data and as a result tend to consume excessive power. To address these shortcomings, neuromorphic sensors have been developed. These sensors mimic the neuro-biological architecture of sensory organs using aVLSI (analog Very Large Scale Integration) and generate asynchronous spiking output that represents sensing information in ways that are similar to neural signals. This allows for much lower power consumption due to an ability to extract useful sensory information from sparse captured data. The foundation for research in neuromorphic sensors was laid more than two decades ago, but recent developments in understanding of biological sensing and advanced electronics, have stimulated research on sophisticated neuromorphic sensors that provide numerous advantages over conventional sensors. In this paper, we review the current state-of-the-art in neuromorphic implementation of vision, auditory, and olfactory sensors and identify key contributions across these fields. Bringing together these key contributions we suggest a future research direction for further development of the neuromorphic sensing field.

  2. A Review of Current Neuromorphic Approaches for Vision, Auditory, and Olfactory Sensors

    PubMed Central

    Vanarse, Anup; Osseiran, Adam; Rassau, Alexander

    2016-01-01

    Conventional vision, auditory, and olfactory sensors generate large volumes of redundant data and as a result tend to consume excessive power. To address these shortcomings, neuromorphic sensors have been developed. These sensors mimic the neuro-biological architecture of sensory organs using aVLSI (analog Very Large Scale Integration) and generate asynchronous spiking output that represents sensing information in ways that are similar to neural signals. This allows for much lower power consumption due to an ability to extract useful sensory information from sparse captured data. The foundation for research in neuromorphic sensors was laid more than two decades ago, but recent developments in understanding of biological sensing and advanced electronics, have stimulated research on sophisticated neuromorphic sensors that provide numerous advantages over conventional sensors. In this paper, we review the current state-of-the-art in neuromorphic implementation of vision, auditory, and olfactory sensors and identify key contributions across these fields. Bringing together these key contributions we suggest a future research direction for further development of the neuromorphic sensing field. PMID:27065784

  3. Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in locusts.

    PubMed

    Guo, Xiaojiao; Ma, Zongyuan; Du, Baozhen; Li, Ting; Li, Wudi; Xu, Lingling; He, Jing; Kang, Le

    2018-03-22

    Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1-miR-9a-AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling.

  4. Identification of Second Messenger Mediating Signal Transduction in the Olfactory Receptor Cell

    PubMed Central

    Takeuchi, Hiroko; Kurahashi, Takashi

    2003-01-01

    One of the biggest controversial issues in the research of olfaction has been the mechanism underlying response generation to odorants that have been shown to fail to produce cAMP when tested by biochemical assays with olfactory ciliary preparations. Such observations are actually the original source proposing a possibility for the presence of multiple and parallel transduction pathways. In this study the activity of transduction channels in the olfactory cilia was recorded in cells that retained their abilities of responding to odorants that have been reported to produce InsP3 (instead of producing cAMP, and therefore tentatively termed “InsP3 odorants”). At the same time, the cytoplasmic cNMP concentration ([cNMP]i) was manipulated through the photolysis of caged compounds to examine their real-time interactions with odorant responses. Properties of responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each other in their unique characteristics. Reversal potentials of currents were 2 mV for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and voltage (I-V) relations showed slight outward rectification. Both responses showed voltage-dependent adaptation when examined with double pulse protocols. When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied alternatively, responses expressed cross-adaptation with each other. Furthermore, both responses were additive in a manner as predicted quantitatively by the theory that signal transduction is mediated by the increase in cytoplasmic cAMP. With InsP3 odorants, actually, remarkable responses could be detected in a small fraction of cells (∼2%), explaining the observation for a small production of cAMP in ciliary preparations obtained from the entire epithelium. The data will provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:14581582

  5. Modern psychophysical tests to assess olfactory function.

    PubMed

    Eibenstein, A; Fioretti, A B; Lena, C; Rosati, N; Amabile, G; Fusetti, M

    2005-07-01

    The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.

  6. Response Times to Gustatory-Olfactory Flavor Mixtures: Role of Congruence.

    PubMed

    Shepard, Timothy G; Veldhuizen, Maria G; Marks, Lawrence E

    2015-10-01

    A mixture of perceptually congruent gustatory and olfactory flavorants (sucrose and citral) was previously shown to be detected faster than predicted by a model of probability summation that assumes stochastically independent processing of the individual gustatory and olfactory signals. This outcome suggests substantial integration of the signals. Does substantial integration also characterize responses to mixtures of incongruent flavorants? Here, we report simple response times (RTs) to detect brief pulses of 3 possible flavorants: monosodium glutamate, MSG (gustatory: "umami" quality), citral (olfactory: citrus quality), and a mixture of MSG and citral (gustatory-olfactory). Each stimulus (and, on a fraction of trials, water) was presented orally through a computer-operated, automated flow system, and subjects were instructed to press a button as soon as they detected any of the 3 non-water stimuli. Unlike responses previously found to the congruent mixture of sucrose and citral, responses here to the incongruent mixture of MSG and citral took significantly longer (RTs were greater) and showed lower detection rates than the values predicted by probability summation. This outcome suggests that the integration of gustatory and olfactory flavor signals is less extensive when the component flavors are perceptually incongruent rather than congruent, perhaps because incongruent flavors are less familiar. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

    PubMed

    Chaillan, F A; Marchetti, E; Delfosse, F; Roman, F S; Soumireu-Mourat, B

    1997-01-01

    In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

  8. A cortical pathway to olfactory naming: evidence from primary progressive aphasia

    PubMed Central

    Rogalski, Emily; Harrison, Theresa; Mesulam, M.-Marsel; Gottfried, Jay A.

    2013-01-01

    It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language ‘deficit’ is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching

  9. Activity-dependent and graded BACE1 expression in the olfactory epithelium is mediated by the retinoic acid metabolizing enzyme CYP26B1.

    PubMed

    Login, Hande; Butowt, Rafal; Bohm, Staffan

    2015-07-01

    It is well established that environmental influences play a key role in sculpting neuronal connectivity in the brain. One example is the olfactory sensory map of topographic axonal connectivity. While intrinsic odorant receptor signaling in olfactory sensory neurons (OSN) determines anterior-posterior counter gradients of the axonal guidance receptors Neuropilin-1 and Plexin-A1, little is known about stimulus-dependent gradients of protein expression, which correlates with the functional organization of the olfactory sensory map along its dorsomedial (DM)-ventrolateral (VL) axis. Deficiency of the Alzheimer's β-secretase BACE1, which is expressed in a DM(low)-VL(high) gradient, results in OSN axon targeting errors in a DM > VL and gene dose-dependent manner. We show that expression of BACE1 and the all-trans retinoic acid (RA)-degrading enzyme Cyp26B1 form DM-VL counter gradients in the olfactory epithelium. Analyses of mRNA and protein levels in OSNs after naris occlusion, in mice deficient in the olfactory cyclic nucleotide-gated channel and in relation to onset of respiration, show that BACE1 and Cyp26B1 expression in OSNs inversely depend on neuronal activity. Overexpression of a Cyp26B1 or presence of a dominant negative RA receptor transgene selectively in OSNs, inhibit BACE1 expression while leaving the DM(low)-VL(high) gradient of the axonal guidance protein Neuropilin-2 intact. We conclude that stimulus-dependent neuronal activity can control the expression of the RA catabolic enzyme Cyp26B1 and downstream genes such as BACE1. This result is pertinent to an understanding of the mechanisms by which a topographic pattern of connectivity is achieved and modified as a consequence of graded gene expression and sensory experience.

  10. PEGylation of zinc nanoparticles amplifies their ability to enhance olfactory responses to odorant

    PubMed Central

    Singletary, Melissa; Hagerty, Samantha; Muramoto, Shin; Daniels, Yasmine; MacCrehan, William A.; Stan, Gheorghe; Lau, June W.; Pustovyy, Oleg; Globa, Ludmila; Morrison, Edward E.; Sorokulova, Iryna

    2017-01-01

    Olfactory responses are intensely enhanced with the addition of endogenous and engineered primarily-elemental small zinc nanoparticles (NPs). With aging, oxidation of these Zn nanoparticles eliminated the observed enhancement. The design of a polyethylene glycol coating to meet storage requirements of engineered zinc nanoparticles is evaluated to achieve maximal olfactory benefit. The zinc nanoparticles were covered with 1000 g/mol or 400 g/mol molecular weight polyethylene glycol (PEG). Non-PEGylated and PEGylated zinc nanoparticles were tested by electroolfactogram with isolated rat olfactory epithelium and odorant responses evoked by the mixture of eugenol, ethyl butyrate and (±) carvone after storage at 278 K (5 oC), 303 K (30 oC) and 323 K (50 oC). The particles were analyzed by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and laser Doppler velocimetry. Our data indicate that stored ZnPEG400 nanoparticles maintain physiologically-consistent olfactory enhancement for over 300 days. These engineered Nanoparticles support future applications in olfactory research, sensitive detection, and medicine. PMID:29261701

  11. Regeneration of synapses in the olfactory pathway of locusts after antennal deafferentation.

    PubMed

    Wasser, Hannah; Stern, Michael

    2017-10-01

    The olfactory pathway of the locust is capable of fast and precise regeneration on an anatomical level. Following deafferentation of the antenna either of young adult locusts, or of fifth instar nymphs, severed olfactory receptor neurons (ORNs) reinnervate the antennal lobe (AL) and arborize in AL microglomeruli. In the present study we tested whether these regenerated fibers establish functional synapses again. Intracellular recordings from AL projection neurons revealed that the first few odor stimulus evoked postsynaptic responses from regenerated ORNs from day 4-7 post crush on. On average, synaptic connections of regenerated afferents appeared faster in younger locusts operated as fifth instar nymphs than in adults. The proportions of response categories (excitatory vs. inhibitory) changed during regeneration, but were back to normal within 21 days. Odor-evoked oscillating extracellular local field potentials (LFP) were recorded in the mushroom body. These responses, absent after antennal nerve crush, reappeared, in a few animals as soon as 4 days post crush. Odor-induced oscillation patterns were restored within 7 days post crush. Both intra- and extracellular recordings indicate the capability of the locust olfactory system to re-establish synaptic contacts in the antennal lobe after antennal nerve lesion.

  12. Using artificial neural networks to classify unknown volatile chemicals from the firings of insect olfactory sensory neurons.

    PubMed

    Bachtiar, Luqman R; Unsworth, Charles P; Newcomb, Richard D; Crampin, Edmund J

    2011-01-01

    The olfactory system detects volatile chemical compounds, known as odour molecules or odorants. Such odorants have a diverse chemical structure which in turn interact with the receptors of the olfactory system. The insect olfactory system provides a unique opportunity to directly measure the firing rates that are generated by the individual olfactory sensory neurons (OSNs) which have been stimulated by odorants in order to use this data to inform their classification. In this work, we demonstrate that it is possible to use the firing rates from an array of OSNs of the vinegar fly, Drosophila melanogaster, to train an Artificial Neural Network (ANN), as a series of a Multi-Layer Perceptrons (MLPs), to differentiate between eight distinct chemical classes. We demonstrate that the MLPs when trained on 108 odorants, for both clean and 10% noise injected data, can reliably identify 87% of an unseen validation set of chemicals using noise injection. In addition, the noise injected MLPs provide a more accurate level of identification. This demonstrates that a 10% noise injected series of MLPs provides a robust method for classifying chemicals from the firing rates of OSNs and paves the way to a future realisation of an artificial olfactory biosensor.

  13. Structure of the principal olfactory tract.

    PubMed

    Gil-Carcedo, L M; Vallejo, L A; Gil-Carcedo, E

    2000-01-01

    Although the purpose and importance of the sense of smell in human beings has not been totally clarified, it is one of the principal information channels in macrosmatic animals. It was the first long-distance information system to have appeared in phylogenetic evolution. The objective of this article is to deepen the knowledge of the pathways that join the olfactory epithelium with the cortical olfaction areas, to better understand olfactory dysfunction in human beings. Differential staining and marking techniques were applied to histologic sections obtained from 155 animals of different species, to study the different connections existing among olfactory tract components. Our study of the connections between the olfactory mucosa and the principal olfactory bulb deserves special mention. The distribution of second neuron connections of the olfactory tract with the central nervous system is quite complex and diffuse. This indicates an interrelation between the sense of smell and a multitude of functions. These connections seem to be of different quantitative importance according to species, but qualitatively they exist in both human beings and other macrosmatic animals.

  14. Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in the Prostate-Specific G-Protein Coupled Receptor (PSGR).

    PubMed

    Wolf, Steffen; Jovancevic, Nikolina; Gelis, Lian; Pietsch, Sebastian; Hatt, Hanns; Gerwert, Klaus

    2017-11-22

    We analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor with a known chemically near identic antagonist/agonist pair, α- and β-ionone. Using a combined theoretical and experimental approach, we propose that this receptor is activated by a ligand-induced rearrangement of a protein-internal hydrogen bond network. Surprisingly, this rearrangement is not induced by interaction of the ligand with the network, but by dynamic van der Waals contacts of the ligand with the involved amino acid side chains, altering their conformations and intraprotein connectivity. Ligand recognition in this GPCR is therefore highly stereo selective, but seemingly lacks any ligand recognition via polar contacts. A putative olfactory receptor-based drug design scheme will have to take this unique mode of protein/ligand action into account.

  15. [Posttraumatic anosmia: olfactory event related potentials and MRI evaluation].

    PubMed

    Liu, Jian-Feng; You, Hui; Ni, Dao-Feng; Zhang, Qiu-Hang; Yang, Da-Zhang; Wang, Na-Ya

    2008-03-01

    Using olfactory event related potentials (OERP) and magnetic resonance to evaluate olfactory function in patients with posttraumatic anosmia. Twenty four patients with posttraumatic anosmia were reviewed retrospectively. A thorough medical history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, brain computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Subjective olfactory testing indicated 20 of 24 patients were birhinal anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was monorhinal), except 4 cases with single nostril. Magnetic resonance imaging revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital gyrus (67%), olfactory tracts (8%) and temporal lobes (8%). OERP can objectively evaluate posttraumatic olfactory function, and magnetic resonance of olfactory pathway can precisely identify the location and extent of injures.

  16. Aversive odorant causing appetite decrease downregulates tyrosine decarboxylase gene expression in the olfactory receptor neuron of the blowfly, Phormia regina

    NASA Astrophysics Data System (ADS)

    Ishida, Yuko; Ozaki, Mamiko

    2012-01-01

    In the blowfly Phormia regina, exposure to d-limonene for 5 days during feeding inhibits proboscis extension reflex behavior due to decreasing tyramine (TA) titer in the brain. TA is synthesized by tyrosine decarboxylase (Tdc) and catalyzed into octopamine (OA) by TA ß-hydroxylase (Tbh). To address the mechanisms of TA titer regulation in the blowfly, we cloned Tdc and Tbh cDNAs from P. regina (PregTdc and PregTbh). The deduced amino acid sequences of both proteins showed high identity to those of the corresponding proteins from Drosophila melanogaster at the amino acid level. PregTdc was expressed in the antenna, labellum, and tarsus whereas PregTbh was expressed in the head, indicating that TA is mainly synthesized in the sensory organs whereas OA is primarily synthesized in the brain. d-Limonene exposure significantly decreased PregTdc expression in the antenna but not in the labellum and the tarsus, indicating that PregTdc expressed in the antenna is responsible for decreasing TA titer. PregTdc-like immunoreactive material was localized in the thin-walled sensillum. In contrast, the OA/TA receptor (PregOAR/TAR) was localized to the thick-walled sensillum. The results indicated that d-limonene inhibits PregTdc expression in the olfactory receptor neurons in the thin-walled sensilla, likely resulting in reduced TA levels in the receptor neurons in the antenna. TA may be transferred from the receptor neuron to the specific synaptic junction in the antennal lobe of the brain through the projection neurons and play a role in conveying the aversive odorant information to the projection and local neurons.

  17. Alterations of brain grey matter density and olfactory bulb volume in patients with olfactory loss after traumatic brain injury.

    PubMed

    Han, Pengfei; Winkler, Nicole; Hummel, Cornelia; Hähner, Antje; Gerber, Johannes; Hummel, Thomas

    2018-04-27

    Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the grey matter (GM) density was examined for twenty-two TBI patients with hyposmia, twenty-four TBI patients with anosmia, and twenty-two age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2 weighted coronal slices using a standardized protocol. Brain lesions in the olfactory relevant areas were also examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC) and the temporal lobe pole, as compared to patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared to controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction compared to healthy controls. Smaller OB volumes were found for patients with olfactory loss as compared to controls. TBI patients with anosmia had the smallest OB volumes which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely depend on the location and severity of brain lesions in olfactory relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

  18. Phosphoinositide-3-Kinase Is the Primary Mediator of Phosphoinositide-Dependent Inhibition in Mammalian Olfactory Receptor Neurons

    PubMed Central

    Ukhanov, Kirill; Corey, Elizabeth; Ache, Barry W.

    2016-01-01

    Odorants inhibit as well as excite primary olfactory receptor neurons (ORNs) in many animal species. Growing evidence suggests that inhibition of mammalian ORNs is mediated by phosphoinositide (PI) signaling through activation of phosphoinositide 3-kinase (PI3K), and that canonical adenylyl cyclase III signaling and PI3K signaling interact to provide the basis for ligand-induced selective signaling. As PI3K is known to act in concert with phospholipase C (PLC) in some cellular systems, the question arises as to whether they work together to mediate inhibitory transduction in mammalian ORNs. The present study is designed to test this hypothesis. While we establish that multiple PLC isoforms are expressed in the transduction zone of rat ORNs, that odorants can activate PLC in ORNs in situ, and that pharmacological blockade of PLC enhances the excitatory response to an odorant mixture in some ORNs in conjunction with PI3K blockade, we find that by itself PLC does not account for an inhibitory response. We conclude that PLC does not make a measurable independent contribution to odor-evoked inhibition, and that PI3K is the primary mediator of PI-dependent inhibition in mammalian ORNs. PMID:27147969

  19. A Closer Look at Acid-Base Olfactory Titrations

    ERIC Educational Resources Information Center

    Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

    2005-01-01

    Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

  20. Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents

    PubMed Central

    2009-01-01

    Olfaction is essential for the survival of animals. Versatile odour molecules in the environment are received by olfactory receptors (ORs), which form the largest multigene family in vertebrates. Identification of the entire repertories of OR genes using bioinformatics methods from the whole-genome sequences of diverse organisms revealed that the numbers of OR genes vary enormously, ranging from ~1,200 in rats and ~400 in humans to ~150 in zebrafish and ~15 in pufferfish. Most species have a considerable fraction of pseudogenes. Extensive phylogenetic analyses have suggested that the numbers of gene gains and losses are extremely large in the OR gene family, which is a striking example of the birth-and-death evolution. It appears that OR gene repertoires change dynamically, depending on each organism's living environment. For example, higher primates equipped with a well-developed vision system have lost a large number of OR genes. Moreover, two groups of OR genes for detecting airborne odorants greatly expanded after the time of terrestrial adaption in the tetrapod lineage, whereas fishes retain diverse repertoires of genes that were present in aquatic ancestral species. The origin of vertebrate OR genes can be traced back to the common ancestor of all chordate species, but insects, nematodes and echinoderms utilise distinctive families of chemoreceptors, suggesting that chemoreceptor genes have evolved many times independently in animal evolution. PMID:20038498

  1. No Sensory Compensation for Olfactory Memory: Differences between Blind and Sighted People.

    PubMed

    Sorokowska, Agnieszka; Karwowski, Maciej

    2017-01-01

    Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people.

  2. No Sensory Compensation for Olfactory Memory: Differences between Blind and Sighted People

    PubMed Central

    Sorokowska, Agnieszka; Karwowski, Maciej

    2017-01-01

    Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people. PMID:29276494

  3. Transcriptomes of Mouse Olfactory Epithelium Reveal Sexual Differences in Odorant Detection

    PubMed Central

    Shiao, Meng-Shin; Chang, Andrew Ying-Fei; Liao, Ben-Yang; Ching, Yung-Hao; Lu, Mei-Yeh Jade; Chen, Stella Maris; Li, Wen-Hsiung

    2012-01-01

    To sense numerous odorants and chemicals, animals have evolved a large number of olfactory receptor genes (Olfrs) in their genome. In particular, the house mouse has ∼1,100 genes in the Olfr gene family. This makes the mouse a good model organism to study Olfr genes and olfaction-related genes. To date, whether male and female mice possess the same ability in detecting environmental odorants is still unknown. Using the next generation sequencing technology (paired-end mRNA-seq), we detected 1,088 expressed Olfr genes in both male and female olfactory epithelium. We found that not only Olfr genes but also odorant-binding protein (Obp) genes have evolved rapidly in the mouse lineage. Interestingly, Olfr genes tend to express at a higher level in males than in females, whereas the Obp genes clustered on the X chromosome show the opposite trend. These observations may imply a more efficient odorant-transporting system in females, whereas a more active Olfr gene expressing system in males. In addition, we detected the expression of two genes encoding major urinary proteins, which have been proposed to bind and transport pheromones or act as pheromones in mouse urine. This observation suggests a role of main olfactory system (MOS) in pheromone detection, contrary to the view that only accessory olfactory system (AOS) is involved in pheromone detection. This study suggests the sexual differences in detecting environmental odorants in MOS and demonstrates that mRNA-seq provides a powerful tool for detecting genes with low expression levels and with high sequence similarities. PMID:22511034

  4. Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

    ERIC Educational Resources Information Center

    Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

    2004-01-01

    The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

  5. The Odorant Receptor Co-Receptor from the Bed Bug, Cimex lectularius L

    PubMed Central

    Hansen, Immo A.; Rodriguez, Stacy D.; Drake, Lisa L.; Price, David P.; Blakely, Brittny N.; Hammond, John I.; Tsujimoto, Hitoshi; Monroy, Erika Y.; Maio, William A.; Romero, Alvaro

    2014-01-01

    Recently, the bed bug, Cimex lectularius L. has re-emerged as a serious and growing problem in many parts of the world. Presence of resistant bed bugs and the difficulty to eliminate them has renewed interest in alternative control tactics. Similar to other haematophagous arthropods, bed bugs rely on their olfactory system to detect semiochemicals in the environment. Previous studies have morphologically characterized olfactory organs of bed bugs’ antenna and have physiologically evaluated the responses of olfactory receptor neurons (ORNs) to host-derived chemicals. To date, odorant binding proteins (OBPs) and odorant receptors (ORs) associated with these olfaction processes have not been studied in bed bugs. Chemoreception in insects requires formation of heteromeric complexes of ORs and a universal OR coreceptor (Orco). Orco is the constant chain of every odorant receptor in insects and is critical for insect olfaction but does not directly bind to odorants. Orco agonists and antagonists have been suggested as high-value targets for the development of novel insect repellents. In this study, we have performed RNAseq of bed bug sensory organs and identified several odorant receptors as well as Orco. We characterized Orco expression and investigated the effect of chemicals targeting Orco on bed bug behavior and reproduction. We have identified partial cDNAs of six C. lectularius OBPs and 16 ORs. Full length bed bug Orco was cloned and sequenced. Orco is widely expressed in different parts of the bed bug including OR neurons and spermatozoa. Treatment of bed bugs with the agonist VUAA1 changed bed bug pheromone-induced aggregation behavior and inactivated spermatozoa. We have described and characterized for the first time OBPs, ORs and Orco in bed bugs. Given the importance of these molecules in chemoreception of this insect they are interesting targets for the development of novel insect behavior modifiers. PMID:25411789

  6. The odorant receptor co-receptor from the bed bug, Cimex lectularius L.

    PubMed

    Hansen, Immo A; Rodriguez, Stacy D; Drake, Lisa L; Price, David P; Blakely, Brittny N; Hammond, John I; Tsujimoto, Hitoshi; Monroy, Erika Y; Maio, William A; Romero, Alvaro

    2014-01-01

    Recently, the bed bug, Cimex lectularius L. has re-emerged as a serious and growing problem in many parts of the world. Presence of resistant bed bugs and the difficulty to eliminate them has renewed interest in alternative control tactics. Similar to other haematophagous arthropods, bed bugs rely on their olfactory system to detect semiochemicals in the environment. Previous studies have morphologically characterized olfactory organs of bed bugs' antenna and have physiologically evaluated the responses of olfactory receptor neurons (ORNs) to host-derived chemicals. To date, odorant binding proteins (OBPs) and odorant receptors (ORs) associated with these olfaction processes have not been studied in bed bugs. Chemoreception in insects requires formation of heteromeric complexes of ORs and a universal OR coreceptor (Orco). Orco is the constant chain of every odorant receptor in insects and is critical for insect olfaction but does not directly bind to odorants. Orco agonists and antagonists have been suggested as high-value targets for the development of novel insect repellents. In this study, we have performed RNAseq of bed bug sensory organs and identified several odorant receptors as well as Orco. We characterized Orco expression and investigated the effect of chemicals targeting Orco on bed bug behavior and reproduction. We have identified partial cDNAs of six C. lectularius OBPs and 16 ORs. Full length bed bug Orco was cloned and sequenced. Orco is widely expressed in different parts of the bed bug including OR neurons and spermatozoa. Treatment of bed bugs with the agonist VUAA1 changed bed bug pheromone-induced aggregation behavior and inactivated spermatozoa. We have described and characterized for the first time OBPs, ORs and Orco in bed bugs. Given the importance of these molecules in chemoreception of this insect they are interesting targets for the development of novel insect behavior modifiers.

  7. Involvement of glutamatergic N-methyl-d-aspartate receptors in the expression of increased head-dipping behaviors in the hole-board tests of olfactory bulbectomized mice.

    PubMed

    Hirose, Noritaka; Saitoh, Akiyoshi; Kamei, Junzo

    2016-10-01

    Olfactory bulbectomized (OB) mice produce agitated anxiety-like behaviors in the hole-board test, which was expressed by an increase in head-dipping counts and a decrease in head-dipping latencies. However, the associated mechanisms remain unclear. In the present study, MK-801 (10, 100μg/kg), a selective N-methyl-d-aspartate (NMDA) receptor antagonist, significantly and dose-dependently suppressed the increased head-dipping behaviors in OB mice, without affecting sham mice. Similar results were obtained with another selective NMDA receptor antagonist D-AP5 treatment in OB mice. On the other hand, muscimol, a selective aminobutyric acid type A (GABAA) receptor agonist produced no effects on these hyperemotional behaviors in OB mice at a dose (100μg/kg) that produced anxiolytic-like effects in sham mice. Interestingly, glutamine contents and glutamine/glutamate ratios were significantly increased in the amygdala and frontal cortex of OB mice compared to sham mice. Based on these results, we concluded that the glutamatergic NMDA receptors are involved in the expression of increased head-dipping behaviors in the hole-board tests of OB mice. Accordingly, the changes in glutamatergic transmission in frontal cortex and amygdala may play important roles in the expression of these abnormal behaviors in OB mice. Copyright © 2016. Published by Elsevier B.V.

  8. [Odor sensing system and olfactory display].

    PubMed

    Nakamoto, Takamichi

    2014-01-01

    In this review, an odor sensing system and an olfactory display are introduced into people in pharmacy. An odor sensing system consists of an array of sensors with partially overlapping specificities and pattern recognition technique. One of examples of odor sensing systems is a halitosis sensor which quantifies the mixture composition of three volatile sulfide compounds. A halitosis sensor was realized using a preconcentrator to raise sensitivity and an electrochemical sensor array to suppress the influence of humidity. Partial least squares (PLS) method was used to quantify the mixture composition. The experiment reveals that the sufficient accuracy was obtained. Moreover, the olfactory display, which present scents to human noses, is explained. A multi-component olfactory display enables the presentation of a variety of smells. The two types of multi-component olfactory display are described. The first one uses many solenoid valves with high speed switching. The valve ON frequency determines the concentration of the corresponding odor component. The latter one consists of miniaturized liquid pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable olfactory display without smell persistence. Finally, the application of the olfactory display is demonstrated. Virtual ice cream shop with scents was made as a content of interactive art. People can enjoy harmony among vision, audition and olfaction. In conclusion, both odor sensing system and olfactory display can contribute to the field of human health care.

  9. Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb.

    PubMed

    Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L; Shepherd, Gordon M; Migliore, Michele

    2016-01-01

    The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

  10. Variant ionotropic receptors are expressed in olfactory sensory neurons of coeloconic sensilla on the antenna of the desert locust (Schistocerca gregaria).

    PubMed

    Guo, Mei; Krieger, Jürgen; Große-Wilde, Ewald; Mißbach, Christine; Zhang, Long; Breer, Heinz

    2013-01-01

    The behaviour of the desert locust, Schistocera gregaria, is largely directed by volatile olfactory cues. The relevant odorants are detected by specialized antennal sensory neurons which project their sensory dendrites into hair-like structures, the sensilla. Generally, the responsiveness of the antennal chemosensory cells is determined by specific receptors which may be either odorant receptors (ORs) or variant ionotropic receptors (IRs). Previously, we demonstrated that in locust the co-receptor for ORs (ORco) is only expressed in cells of sensilla basiconica and sensilla trichodea, suggesting that cells in sensilla coeloconica may express different types of chemosensory receptors. In this study, we have identified the genes of S. gregaria which encode homologues of co-receptors for the variant ionotropic receptors, the subtypes IR8a and IR25a. It was found that both subtypes, SgreIR8a and SgreIR25a, are expressed in the antennae of all five nymphal stages and in adults. Attempts to assign the relevant cell types by means of in situ hybridization revealed that SgreIR8a and SgreIR25a are expressed in cells of sensilla coeloconica. Double fluorescence in situ hybridization experiments disclosed that the two IR-subtypes are co-expressed in some cells of this sensillum type. Expression of SgreIR25a was also found in some of the sensilla chaetica, however, neither SgreIR25a nor SgreIR8a was found to be expressed in sensilla basiconica and sensilla trichodea. This observation was substantiated by the results of double FISH experiments demonstrating that cells expressing SgreIR8a or SgreIR25a do not express ORco. These results support the notion that the antenna of the desert locust employs two different populations of OSNs to sense odors; cells which express IRs in sensilla coeloconica and cells which express ORs in sensilla basiconica and sensilla trichodea.

  11. Olfactory modulation by dopamine in the context of aversive learning

    PubMed Central

    Riffell, Jeffrey A.; Martin, Joshua P.; Gage, Stephanie L.; Nighorn, Alan J.

    2012-01-01

    The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. PMID:22552185

  12. Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes

    PubMed Central

    Butler, Julie M.; Field, Karen E.; Maruska, Karen P.

    2016-01-01

    Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni, goldfish Carassius auratus, and the Mexican blind cavefish Astyanax mexicanus. To examine the impact of CoCl2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl2 solutions. In addition, we examined brain activation in olfactory processing regions of A. burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl2 had decreased DASPEI staining of the olfactory epithelium, and in A. burtoni, cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of CoCl2 in future

  13. The "olfactory mirror" and other recent attempts to demonstrate self-recognition in non-primate species.

    PubMed

    Gallup, Gordon G; Anderson, James R

    2018-03-01

    The recent attempt by Horowitz (2017) to develop an "olfactory mirror" test of self-recognition in domestic dogs raises some important questions about the kinds of data that are required to provide definitive evidence for self-recognition in dogs and other species. We conclude that the "olfactory mirror" constitutes a compelling analog to the mark test for mirror self-recognition in primates, but despite claims to the contrary neither dogs, elephants, dolphins, magpies, horses, manta rays, squid, nor ants have shown compelling, reproducible evidence for self-recognition in any modality. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Olfactory channels associated with the Drosophila maxillary palp mediate short- and long-range attraction

    PubMed Central

    Dweck, Hany KM; Ebrahim, Shimaa AM; Khallaf, Mohammed A; Koenig, Christopher; Farhan, Abu; Stieber, Regina; Weißflog, Jerrit; Svatoš, Aleš; Grosse-Wilde, Ewald

    2016-01-01

    The vinegar fly Drosophila melanogaster is equipped with two peripheral olfactory organs, antenna and maxillary palp. The antenna is involved in finding food, oviposition sites and mates. However, the functional significance of the maxillary palp remained unknown. Here, we screened the olfactory sensory neurons of the maxillary palp (MP-OSNs) using a large number of natural odor extracts to identify novel ligands for each MP-OSN type. We found that each type is the sole or the primary detector for a specific compound, and detects these compounds with high sensitivity. We next dissected the contribution of MP-OSNs to behaviors evoked by their key ligands and found that MP-OSNs mediate short- and long-range attraction. Furthermore, the organization, detection and olfactory receptor (Or) genes of MP-OSNs are conserved in the agricultural pest D. suzukii. The novel short and long-range attractants could potentially be used in integrated pest management (IPM) programs of this pest species. DOI: http://dx.doi.org/10.7554/eLife.14925.001 PMID:27213519

  15. The Evolution of Olfactory Gene Families in Drosophila and the Genomic Basis of chemical-Ecological Adaptation in Drosophila suzukii

    PubMed Central

    Ramasamy, Sukanya; Ometto, Lino; Crava, Cristina M.; Revadi, Santosh; Kaur, Rupinder; Horner, David S.; Pisani, Davide; Dekker, Teun; Anfora, Gianfranco; Rota-Stabelli, Omar

    2016-01-01

    How the evolution of olfactory genes correlates with adaption to new ecological niches is still a debated topic. We explored this issue in Drosophila suzukii, an emerging model that reproduces on fresh fruit rather than in fermenting substrates like most other Drosophila. We first annotated the repertoire of odorant receptors (ORs), odorant binding proteins (OBPs), and antennal ionotropic receptors (aIRs) in the genomes of two strains of D. suzukii and of its close relative Drosophila biarmipes. We then analyzed these genes on the phylogeny of 14 Drosophila species: whereas ORs and OBPs are characterized by higher turnover rates in some lineages including D. suzukii, aIRs are conserved throughout the genus. Drosophila suzukii is further characterized by a non-random distribution of OR turnover on the gene phylogeny, consistent with a change in selective pressures. In D. suzukii, we found duplications and signs of positive selection in ORs with affinity for short-chain esters, and loss of function of ORs with affinity for volatiles produced during fermentation. These receptors—Or85a and Or22a—are characterized by divergent alleles in the European and American genomes, and we hypothesize that they may have been replaced by some of the duplicated ORs in corresponding neurons, a hypothesis reciprocally confirmed by electrophysiological recordings. Our study quantifies the evolution of olfactory genes in Drosophila and reveals an array of genomic events that can be associated with the ecological adaptations of D. suzukii. PMID:27435796

  16. Giant Olfactory Meningiomas

    PubMed Central

    d'Avella, Domenico; Salpietro, Francesco M.; Alafaci, Cetty; Tomasello, Francesco

    1999-01-01

    Olfactory groove meningiomas may attain surprisingly large size. The subfrontal approach is currently the route preferred by most neurosurgeons for their excision. The pterional-transsylvian route represents an alternate exposure for microsurgery of frontobasal tumors. Although this approach has been already described for olfactory meningiomas, tumors of giant size were not specifically addressed in the literature. We report the application of the pterional-transsylvian approach in six patients with giant olfactory meningiomas. This series is unique because it includes only patients with tumors exceeding 6 cm in diameter with bilateral symmetrical development. A radical removal was achieved in all patients and all of them made a full recovery. To investigate the relevance of the pterional-transsylvian approach for minimizing surgical morbidity, a magnetic resonance imaging protocol was designed to characterize even subtle postoperative frontal lobe structural changes. These changes, limited to the frontal lobe ipsilateral to exposure and localized in specific anatomical domains of the prefrontal area, included cystic degenerative alterations, parenchymal gliosis, and associated persistent white matter edema. Results from the present series strengthen the usefulness of the pterional-transsylvian approach as a safe surgical route for lesions affecting the anterior skull base, even with huge bilateral symmetrical expansion, such as giant olfactory meningiomas. ImagesFigure 1Figure 2Figure 3p26-bFigure 4p27-bFigure 5Figure 6Figure 7 PMID:17171078

  17. Non-ionotropic signaling by the NMDA receptor: controversy and opportunity.

    PubMed

    Gray, John A; Zito, Karen; Hell, Johannes W

    2016-01-01

    Provocative emerging evidence suggests that the N-methyl-d-aspartate (NMDA) receptor can signal in the absence of ion flux through the receptor. This non-ionotropic signaling is thought to be due to agonist-induced conformational changes in the receptor, independently of channel opening. Non-ionotropic NMDA receptor signaling has been proposed to be sufficient to induce synaptic long-term depression (LTD), directly challenging the decades-old model that prolonged low-level calcium influx is required to induce LTD. Here, we briefly review these recent findings, focusing primarily on the potential role of non-ionotropic signaling in NMDA receptor-mediated LTD. Further reports concerning additional roles of non-ionotropic NMDA receptor signaling are also discussed. If validated, this new view of NMDA receptor-mediated signaling will usher in an exciting new era of exploring synapse function and dysfunction.

  18. Non-ionotropic signaling by the NMDA receptor: controversy and opportunity

    PubMed Central

    Gray, John A.; Zito, Karen; Hell, Johannes W.

    2016-01-01

    Provocative emerging evidence suggests that the N-methyl-d-aspartate (NMDA) receptor can signal in the absence of ion flux through the receptor. This non-ionotropic signaling is thought to be due to agonist-induced conformational changes in the receptor, independently of channel opening. Non-ionotropic NMDA receptor signaling has been proposed to be sufficient to induce synaptic long-term depression (LTD), directly challenging the decades-old model that prolonged low-level calcium influx is required to induce LTD. Here, we briefly review these recent findings, focusing primarily on the potential role of non-ionotropic signaling in NMDA receptor-mediated LTD. Further reports concerning additional roles of non-ionotropic NMDA receptor signaling are also discussed. If validated, this new view of NMDA receptor-mediated signaling will usher in an exciting new era of exploring synapse function and dysfunction. PMID:27303637

  19. Olfactory deposition of inhaled nanoparticles in humans

    PubMed Central

    Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

    2016-01-01

    Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

  20. Prevalence of olfactory impairment in older adults.

    PubMed

    Murphy, Claire; Schubert, Carla R; Cruickshanks, Karen J; Klein, Barbara E K; Klein, Ronald; Nondahl, David M

    2002-11-13

    Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. To determine the prevalence of olfactory impairment in older adults. A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.

  1. Bioflavoring by non-conventional yeasts in sequential beer fermentations.

    PubMed

    Holt, Sylvester; Mukherjee, Vaskar; Lievens, Bart; Verstrepen, Kevin J; Thevelein, Johan M

    2018-06-01

    Non-conventional yeast species have great capacity for producing diverse flavor profiles in production of alcoholic beverages, but their potential for beer brewing, in particular in consecutive fermentations with Saccharomyces cerevisiae, has only poorly been explored. We have screened 17 non-conventional yeast species for production of an appealing profile of flavor esters and phenolics in the first phase of alcoholic fermentation, followed by inoculation with S. cerevisiae to complete the fermentation. For measurement of phenolic compounds and their precursors we developed an improved and highly sensitive methodology. The results show that non-conventional yeast species possess promising potential for enhancement of desirable flavors in beer production. Notable examples are increasing isoamyl acetate (fruity, banana flavor) by application of P. kluyverii, augmenting ethyl phenolic compounds (spicy notes) with Brettanomyces species and enhancing 4-vinyl guaiacol (clove-like aroma) with T. delbrueckii. All Pichia strains also produced high levels of ethyl acetate (solvent-like flavor). This might be selectively counteracted by selection of an appropriate S. cerevisiae strain for the second fermentation phase, which lowers total ester profile. Hence, optimization of the process conditions and/or proper strain selection in sequentially inoculated fermentations are required to unlock the full potential for aroma improvement by the non-conventional yeast species. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Olfactory dysfunction, olfactory bulb pathology and urban air pollution

    PubMed Central

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

    2010-01-01

    Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

  3. Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

    PubMed

    Kiparizoska, Sara; Ikuta, Toshikazu

    2017-09-01

    Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  4. Relationship between uninasal anatomy and uninasal olfactory ability.

    PubMed

    Hornung, D E; Leopold, D A

    1999-01-01

    To examine the relationship between uninasal anatomy and olfactory ability. A stepwise analysis of variance was used to regress the logarithm of the percentage of correct responses on the Odorant Confusion Matrix (a measure of olfactory ability) against the logarithm of nasal volume measurements determined from computed tomographic scans. Nineteen patients with hyposmia whose olfactory losses were thought to be related to conductive disorders. After correcting for sex differences, a mathematical model was developed in which the volume of 6 regions of the nasal cavity, 6 first-order interactions, and 3 second-order interactions accounted for 97% of the variation in the measure of olfactory ability. Increases in the size of compartments of the nasal cavity around the olfactory cleft generally increase olfactory ability. Also, anatomical differences in the nasal cavities of men and women may account, in part, for sex differences in olfactory ability.

  5. Cortical Feedback Control of Olfactory Bulb Circuits

    PubMed Central

    Boyd, Alison M.; Sturgill, James F.; Poo, Cindy; Isaacson, Jeffry S.

    2013-01-01

    SUMMARY Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

  6. Olfactory acuity in theropods: palaeobiological and evolutionary implications.

    PubMed

    Zelenitsky, Darla K; Therrien, François; Kobayashi, Yoshitsugu

    2009-02-22

    This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.

  7. Olfactory acuity in theropods: palaeobiological and evolutionary implications

    PubMed Central

    Zelenitsky, Darla K.; Therrien, François; Kobayashi, Yoshitsugu

    2008-01-01

    This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds. PMID:18957367

  8. The prevalence of olfactory dysfunction in chronic rhinosinusitis.

    PubMed

    Kohli, Preeti; Naik, Akash N; Harruff, E Emily; Nguyen, Shaun A; Schlosser, Rodney J; Soler, Zachary M

    2017-02-01

    Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study were to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. A total of 47 articles were included in a systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin' Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96 ± 7.11 using the 40-item Smell Identification Test, 8.60 ± 2.81 using the Brief Smell Identification Test, 21.96 ± 8.88 using total Sniffin' Sticks score, 5.65 ± 1.51 using Sniffin' Sticks-Threshold, 9.21 ± 4.63 using Sniffin' Sticks-Discrimination, 9.47 ± 3.92 using Sniffin' Sticks-Identification, and 8.90 ± 5.14 using the Questionnaire for Olfactory Disorders-Negative Statements. In CRS populations, a significant percentage of patients experience olfactory dysfunction, and mean olfactory scores are within the dysosmic range. Laryngoscope, 2016 127:309-320, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. The Prevalence of Olfactory Dysfunction in Chronic Rhinosinusitis

    PubMed Central

    Kohli, Preeti; Naik, Akash N.; Harruff, E. Emily; Nguyen, Shaun A.; Schlosser, Rodney J.; Soler, Zachary M.

    2016-01-01

    Objective Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study are to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. Data Sources A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Review Methods Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. Results A total of 47 articles were included in systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin’ Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96±7.11 using the 40-item Smell Identification Test, 8.60±2.81 using the Brief Smell Identification Test, 21.96±8.88 using total Sniffin’ sticks score, 5.65±1.51 using Sniffin’ Sticks threshold, 9.21±4.63 using Sniffin’ Sticks discrimination, 9.47±3.92 using Sniffin’ Sticks Identification, and 8.90±5.14 using the questionnaire for olfactory disorders-negative statements. Conclusion In chronic rhinosinusitis populations, a significant percentage of patients experience olfactory dysfunction and mean olfactory scores are within the dysosmic range. PMID:27873345

  10. Non-conventional technologies for data collection in Brazilian dissertations and theses.

    PubMed

    Salvador, Pétala Tuani Candido de Oliveira; Rodrigues, Cláudia Cristiane Filgueira Martins; de Lima, Kálya Yasmine Nunes; Alves, Kisna Yasmin Andrade; Santos, Viviane Euzébia Pereira

    2015-01-01

    to characterize non-conventional technologies used for data collection of dissertations and theses available in the Catalog of Theses and Dissertations (CEPEn) of the Brazilian Nursing Association (ABEn). this is a documentary research, whose data were collected in the catalogs of theses and dissertations available at the ABEn website, from Volumes XIX to XXI. The indicators collected were: academic level; educational institution; year; qualification of the author; setting; non-conventional technology used; type of technology; association with conventional techniques; methodological design; benefits and methodological limitations. from a total of 6346 studies, only 121 (1.91%) used non-conventional technologies for data collection, representing the fi nal sample of the study. it is concluded that Brazilian Nursing researches still need methodological innovations for data collection.

  11. Identification and functional characterization of a sex pheromone receptor in the silkmoth Bombyx mori

    PubMed Central

    Sakurai, Takeshi; Nakagawa, Takao; Mitsuno, Hidefumi; Mori, Hajime; Endo, Yasuhisa; Tanoue, Shintarou; Yasukochi, Yuji; Touhara, Kazushige; Nishioka, Takaaki

    2004-01-01

    Sex pheromones released by female moths are detected with high specificity and sensitivity in the olfactory sensilla of antennae of conspecific males. Bombykol in the silkmoth Bombyx mori was the first sex pheromone to be identified. Here we identify a male-specific G protein-coupled olfactory receptor gene, B. mori olfactory receptor 1 (BmOR-1), that appears to encode a bombykol receptor. The BmOR-1 gene is located on the Z sex chromosome, has an eight-exon/seven-intron structure, and exhibits male-specific expression in the pheromone receptor neurons of male moth antenna during late pupal and adult stages. Bombykol stimulation of Xenopus laevis oocytes expressing BmOR-1 and BmGαq elicited robust dose-dependent inward currents on two-electrode voltage clamp recordings, demonstrating that the binding of bombykol to BmOR-1 leads to the activation of a BmGαq-mediated signaling cascade. Antennae of female moths infected with BmOR-1-recombinant baculovirus showed electrophysiological responses to bombykol but not to bombykal. These results provide evidence that BmOR-1 is a G protein-coupled sex pheromone receptor that recognizes bombykol. PMID:15545611

  12. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system.

    PubMed

    Kaplan, Bernhard A; Lansner, Anders

    2014-01-01

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin-Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian-Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian-Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures.

  13. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system

    PubMed Central

    Kaplan, Bernhard A.; Lansner, Anders

    2014-01-01

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin–Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian–Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian–Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures. PMID

  14. The Genetics of Non-conventional Wine Yeasts: Current Knowledge and Future Challenges

    PubMed Central

    Masneuf-Pomarede, Isabelle; Bely, Marina; Marullo, Philippe; Albertin, Warren

    2016-01-01

    Saccharomyces cerevisiae is by far the most widely used yeast in oenology. However, during the last decade, several other yeasts species has been purposed for winemaking as they could positively impact wine quality. Some of these non-conventional yeasts (Torulaspora delbrueckii, Metschnikowia pulcherrima, Pichia kluyveri, Lachancea thermotolerans, etc.) are now proposed as starters culture for winemakers in mixed fermentation with S. cerevisiae, and several others are the subject of various studies (Hanseniaspora uvarum, Starmerella bacillaris, etc.). Along with their biotechnological use, the knowledge of these non-conventional yeasts greatly increased these last 10 years. The aim of this review is to describe the last updates and the current state-of-art of the genetics of non-conventional yeasts (including S. uvarum, T. delbrueckii, S. bacillaris, etc.). We describe how genomics and genetics tools provide new data into the population structure and biodiversity of non-conventional yeasts in winemaking environments. Future challenges will lie on the development of selection programs and/or genetic improvement of these non-conventional species. We discuss how genetics, genomics and the advances in next-generation sequencing will help the wine industry to develop the biotechnological use of non-conventional yeasts to improve the quality and differentiation of wines. PMID:26793188

  15. The Genetics of Non-conventional Wine Yeasts: Current Knowledge and Future Challenges.

    PubMed

    Masneuf-Pomarede, Isabelle; Bely, Marina; Marullo, Philippe; Albertin, Warren

    2015-01-01

    Saccharomyces cerevisiae is by far the most widely used yeast in oenology. However, during the last decade, several other yeasts species has been purposed for winemaking as they could positively impact wine quality. Some of these non-conventional yeasts (Torulaspora delbrueckii, Metschnikowia pulcherrima, Pichia kluyveri, Lachancea thermotolerans, etc.) are now proposed as starters culture for winemakers in mixed fermentation with S. cerevisiae, and several others are the subject of various studies (Hanseniaspora uvarum, Starmerella bacillaris, etc.). Along with their biotechnological use, the knowledge of these non-conventional yeasts greatly increased these last 10 years. The aim of this review is to describe the last updates and the current state-of-art of the genetics of non-conventional yeasts (including S. uvarum, T. delbrueckii, S. bacillaris, etc.). We describe how genomics and genetics tools provide new data into the population structure and biodiversity of non-conventional yeasts in winemaking environments. Future challenges will lie on the development of selection programs and/or genetic improvement of these non-conventional species. We discuss how genetics, genomics and the advances in next-generation sequencing will help the wine industry to develop the biotechnological use of non-conventional yeasts to improve the quality and differentiation of wines.

  16. Olfactory discrimination: when vision matters?

    PubMed

    Demattè, M Luisa; Sanabria, Daniel; Spence, Charles

    2009-02-01

    Many previous studies have attempted to investigate the effect of visual cues on olfactory perception in humans. The majority of this research has only looked at the modulatory effect of color, which has typically been explained in terms of multisensory perceptual interactions. However, such crossmodal effects may equally well relate to interactions taking place at a higher level of information processing as well. In fact, it is well-known that semantic knowledge can have a substantial effect on people's olfactory perception. In the present study, we therefore investigated the influence of visual cues, consisting of color patches and/or shapes, on people's olfactory discrimination performance. Participants had to make speeded odor discrimination responses (lemon vs. strawberry) while viewing a red or yellow color patch, an outline drawing of a strawberry or lemon, or a combination of these color and shape cues. Even though participants were instructed to ignore the visual stimuli, our results demonstrate that the accuracy of their odor discrimination responses was influenced by visual distractors. This result shows that both color and shape information are taken into account during speeded olfactory discrimination, even when such information is completely task irrelevant, hinting at the automaticity of such higher level visual-olfactory crossmodal interactions.

  17. Terminal-Nerve-Derived Neuropeptide Y Modulates Physiological Responses in the Olfactory Epithelium of Hungry Axolotls (Ambystoma mexicanum)

    PubMed Central

    Mousley, Angela; Polese, Gianluca; Marks, Nikki J.; Eisthen, Heather L.

    2007-01-01

    The vertebrate brain actively regulates incoming sensory information, effectively filtering input and focusing attention toward environmental stimuli that are most relevant to the animal's behavioral context or physiological state. Such centrifugal modulation has been shown to play an important role in processing in the retina and cochlea, but has received relatively little attention in olfaction. The terminal nerve, a cranial nerve that extends underneath the lamina propria surrounding the olfactory epithelium, displays anatomical and neurochemical characteristics that suggest that it modulates activity in the olfactory epithelium. Using immunocytochemical techniques, we demonstrate that neuropeptide Y (NPY) is abundantly present in the terminal nerve in the axolotl (Ambystoma mexicanum), an aquatic salamander. Because NPY plays an important role in regulating appetite and hunger in many vertebrates, we investigated the possibility that NPY modulates activity in the olfactory epithelium in relation to the animal's hunger level. We therefore characterized the full length NPY gene from axolotls to enable synthesis of authentic axolotl NPY for use in electrophysiological experiments. We find that axolotl NPY modulates olfactory epithelial responses evoked by L-glutamic acid, a food-related odorant, but only in hungry animals. Similarly, whole-cell patch-clamp recordings demonstrate that bath application of axolotl NPY enhances the magnitude of a tetrodotoxin-sensitive inward current, but only in hungry animals. These results suggest that expression or activity of NPY receptors in the olfactory epithelium may change with hunger level, and that terminal nerve-derived peptides modulate activity in the olfactory epithelium in response to an animal's changing behavioral and physiological circumstances. PMID:16855098

  18. Terminal nerve-derived neuropeptide y modulates physiological responses in the olfactory epithelium of hungry axolotls (Ambystoma mexicanum).

    PubMed

    Mousley, Angela; Polese, Gianluca; Marks, Nikki J; Eisthen, Heather L

    2006-07-19

    The vertebrate brain actively regulates incoming sensory information, effectively filtering input and focusing attention toward environmental stimuli that are most relevant to the animal's behavioral context or physiological state. Such centrifugal modulation has been shown to play an important role in processing in the retina and cochlea, but has received relatively little attention in olfaction. The terminal nerve, a cranial nerve that extends underneath the lamina propria surrounding the olfactory epithelium, displays anatomical and neurochemical characteristics that suggest that it modulates activity in the olfactory epithelium. Using immunocytochemical techniques, we demonstrate that neuropeptide Y (NPY) is abundantly present in the terminal nerve in the axolotl (Ambystoma mexicanum), an aquatic salamander. Because NPY plays an important role in regulating appetite and hunger in many vertebrates, we investigated the possibility that NPY modulates activity in the olfactory epithelium in relation to the animal's hunger level. We therefore characterized the full-length NPY gene from axolotls to enable synthesis of authentic axolotl NPY for use in electrophysiological experiments. We find that axolotl NPY modulates olfactory epithelial responses evoked by l-glutamic acid, a food-related odorant, but only in hungry animals. Similarly, whole-cell patch-clamp recordings demonstrate that bath application of axolotl NPY enhances the magnitude of a tetrodotoxin-sensitive inward current, but only in hungry animals. These results suggest that expression or activity of NPY receptors in the olfactory epithelium may change with hunger level, and that terminal nerve-derived peptides modulate activity in the olfactory epithelium in response to an animal's changing behavioral and physiological circumstances.

  19. Ionotropic receptors (IRs): chemosensory ionotropic glutamate receptors in Drosophila and beyond.

    PubMed

    Rytz, Raphael; Croset, Vincent; Benton, Richard

    2013-09-01

    Ionotropic Receptors (IRs) are a recently characterized family of olfactory receptors in the fruit fly, Drosophila melanogaster. IRs are not related to insect Odorant Receptors (ORs), but rather have evolved from ionotropic glutamate receptors (iGluRs), a conserved family of synaptic ligand-gated ion channels. Here, we review the expression and function of IRs in Drosophila, highlighting similarities and differences with iGluRs. We also briefly describe the organization of the neuronal circuits in which IRs function, comparing and contrasting them with the sensory pathways expressing ORs. Finally, we summarize the bioinformatic identification and initial characterization of IRs in other species, which imply an evolutionarily conserved role for these receptors in chemosensation in insects and other protostomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Stereochemical study of mouse muscone receptor MOR215-1 and vibrational theory based on statistical physics formalism.

    PubMed

    Ben Khemis, Ismahene; Mechi, Nesrine; Ben Lamine, Abdelmottaleb

    2018-02-10

    In the biosensor system, olfactory receptor sites could be activated by odorant molecules and then the biological interactions are converted into electrical signals by a signal transduction cascade that leads the toopening of ion channels, generating a current that leads into the cilia and depolarizes the membrane. The aim of this paper is to present a new investigation that allows determining the olfactory band using a monolayer adsorption with identical sites modeling which may also describe the static and the dynamic sensitivities through the expression of the olfactory response. Moreover, knowing the size of receptor site in olfactory sensory neurons provides valuable information about the relationship between molecular structure and biological activity. The determination of microreceptors and mesoreceptors is mostly carried out via physical adsorption and the radius is calculated using the Kelvin equation. The mean values of radius obtained from the maximum of the receptor size distributions peaks are 4 nm for ℓ-muscone and 6 nm for d-muscone. Copyright © 2018. Published by Elsevier Ltd.

  1. Stimulation of Electro-Olfactogram Responses in the Main Olfactory Epithelia by Airflow Depend on the Type 3 Adenylyl Cyclase

    PubMed Central

    Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R.

    2012-01-01

    Cilia of olfactory sensory neurons (OSN) are the primary sensory organelles for olfaction. The detection of odorants by the main olfactory epithelium (MOE) depends on coupling of odorant receptors to the type 3 adenylyl cyclase (AC3) in olfactory cilia. We monitored the effect of airflow on electro-olfactogram (EOG) responses and found that the MOE of mice can sense mechanical forces generated by airflow. The airflow-sensitive EOG response in the MOE was attenuated when cAMP was increased by odorants or by forskolin suggesting a common mechanism for airflow and odorant detection. In addition, the sensitivity to airflow was significantly impaired in the MOE from AC3−/− mice. We conclude that AC3 in the MOE is required for detecting the mechanical force of airflow, which in turn may regulate odorant perception during sniffing. PMID:23136416

  2. The Pig Olfactory Brain: A Primer

    PubMed Central

    Feldman, Sanford; Osterberg, Stephen K.

    2016-01-01

    Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals. PMID:26936231

  3. Contrasting Patterns of Evolutionary Diversification in the Olfactory Repertoires of Reptile and Bird Genomes

    PubMed Central

    Vandewege, Michael W.; Mangum, Sarah F.; Gabaldón, Toni; Castoe, Todd A.; Ray, David A.; Hoffmann, Federico G.

    2016-01-01

    Olfactory receptors (ORs) are membrane proteins that mediate the detection of odorants in the environment, and are the largest vertebrate gene family. Comparative studies of mammalian genomes indicate that OR repertoires vary widely, even between closely related lineages, as a consequence of frequent OR gains and losses. Several studies also suggest that mammalian OR repertoires are influenced by life history traits. Sauropsida is a diverse group of vertebrates group that is the sister group to mammals, and includes birds, testudines, squamates, and crocodilians, and represents a natural system to explore predictions derived from mammalian studies. In this study, we analyzed olfactory receptor (OR) repertoire variation among several representative species and found that the number of intact OR genes in sauropsid genomes analyzed ranged over an order of magnitude, from 108 in the green anole to over 1,000 in turtles. Our results suggest that different sauropsid lineages have highly divergent OR repertoire composition that derive from lineage-specific combinations of gene expansions, losses, and retentions of ancestral OR genes. These differences also suggest that varying degrees of adaption related to life history have shaped the unique OR repertoires observed across sauropsid lineages. PMID:26865070

  4. Apolipoprotein E4 causes early olfactory network abnormalities and short-term olfactory memory impairments.

    PubMed

    Peng, Katherine Y; Mathews, Paul M; Levy, Efrat; Wilson, Donald A

    2017-02-20

    While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction. In addition, we have recorded in vivo resting and odor-evoked local field potentials (LPF) from both brain regions and measured corresponding odor response magnitudes in anesthetized young (6-month-old) and middle-aged (12-month-old) ApoE mice. Young ApoE4 compared to ApoE3 mice exhibited a behavioral olfactory deficit coinciding with hyperactive odor-evoked response magnitudes within the OB that were not observed in older ApoE4 mice. Meanwhile, middle-aged ApoE4 compared to ApoE3 mice exhibited heightened response magnitudes in the PCX without a corresponding olfactory deficit, suggesting a shift with aging in ApoE4-driven effects from OB to PCX. Interestingly, the increased ApoE4-specific response in the PCX at middle-age was primarily due to a dampening of baseline spontaneous activity rather than an increase in evoked response power. Our findings indicate that early ApoE4-driven olfactory memory impairments and OB network abnormalities may be a precursor to later network dysfunction in the PCX, a region that not only is targeted early in AD, but may be selectively vulnerable to ApoE4 genotype. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Cortical feedback control of olfactory bulb circuits.

    PubMed

    Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

    2012-12-20

    Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Insect odorant receptors are molecular targets of the insect repellent DEET.

    PubMed

    Ditzen, Mathias; Pellegrino, Maurizio; Vosshall, Leslie B

    2008-03-28

    DEET (N,N-diethyl-meta-toluamide) is the world's most widely used topical insect repellent, with broad effectiveness against most insects. Its mechanism of action and molecular target remain unknown. Here, we show that DEET blocks electrophysiological responses of olfactory sensory neurons to attractive odors in Anopheles gambiae and Drosophila melanogaster. DEET inhibits behavioral attraction to food odors in Drosophila, and this inhibition requires the highly conserved olfactory co-receptor OR83b. DEET inhibits odor-evoked currents mediated by the insect odorant receptor complex, comprising a ligand-binding subunit and OR83b. We conclude that DEET masks host odor by inhibiting subsets of heteromeric insect odorant receptors that require the OR83b co-receptor. The identification of candidate molecular targets for the action of DEET may aid in the design of safer and more effective insect repellents.

  7. Evolutionary changes of the importance of olfaction in cetaceans based on the olfactory marker protein gene.

    PubMed

    Kishida, Takushi; Thewissen, J G M

    2012-01-25

    Odontocetes and mysticetes are two extant suborders of cetaceans. It is reported that the former have no sense of olfaction, while the latter can smell in air. To explain the ecological reason why mysticetes still retain their sense of smell, two hypotheses have been proposed - the echolocation-priority hypothesis, which assumes that the acquisition of echolocation causes the reduction of the importance of olfaction, and the filter-feeder hypothesis, which assumes that olfactory ability is important for filter-feeders to locate their prey because clouds of plankton give off a peculiar odor. The olfactory marker protein (OMP) is almost exclusively expressed in vertebrate olfactory receptor neurons, and is considered to play important roles in olfactory systems. In this study, full-length open reading frames of OMP genes were identified in 6 cetacean species and we analyzed the nonsynonymous to synonymous substitution rate ratio based on the maximum likelihood method. The evolutionary changes of the selective pressures on OMP genes did fit better to the filter-feeder hypothesis than to the echolocation-priority hypothesis. In addition, no pseudogenization mutations are found in all five odontocetes OMP genes investigated in this study. It may suggest that OMP retains some function even in 'anosmic' odontocetes. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Retronasal odor representations in the dorsal olfactory bulb of rats

    PubMed Central

    Gautam, Shree Hari; Verhagen, Justus V.

    2012-01-01

    Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic question is if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthoversus retronasal response patterns. We found that at a physiologically relevant flow rate retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between ortho- and retronasal odor representations in the rat OB. PMID:22674270

  9. Office procedures for quantitative assessment of olfactory function.

    PubMed

    Doty, Richard L

    2007-01-01

    Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.

  10. Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome

    PubMed Central

    Audouze, Karine; Tromelin, Anne; Le Bon, Anne Marie; Belloir, Christine; Petersen, Rasmus Koefoed; Kristiansen, Karsten; Brunak, Søren; Taboureau, Olivier

    2014-01-01

    The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome. PMID:24695519

  11. Emotional stimulation alters olfactory sensitivity and odor judgment.

    PubMed

    Pollatos, Olga; Kopietz, Rainer; Linn, Jennifer; Albrecht, Jessica; Sakar, Vehbi; Anzinger, Andrea; Schandry, Rainer; Wiesmann, Martin

    2007-07-01

    Emotions have a strong influence on the perception of visual and auditory stimuli. Only little is known about the relation between emotional stimulation and olfactory functions. The present study investigated the relationship between the presentation of affective pictures, olfactory functions, and sex. Olfactory performance was assessed in 32 subjects (16 male). Olfactory sensitivity was significantly reduced following unpleasant picture presentation for all subjects and following pleasant picture presentation for male subjects only. Pleasantness and intensity ratings of a neutral suprathreshold odor were related to the valence of the pictures: After unpleasant picture presentation, the odor was rated as less pleasant and more intense, whereas viewing positive pictures induced a significant increase in reported odor pleasantness. We conclude that inducing a negative emotional state reduces olfactory sensitivity. A relation to functional deviations within the primary olfactory cortices is discussed.

  12. Selectivity of odorant receptors in insects

    USDA-ARS?s Scientific Manuscript database

    Insect olfactory receptors (ORs) detect chemical signals, shape neuronal physiology and regulate behavior. Although ORs have been categorized as generalists and specialists based on their ligand spectrum, both electrophysiological studies and recent pharmacological investigations show that ORs spec...

  13. Antennal olfactory sensilla responses to insect chemical repellents in the common bed bug, Cimex lectularius.

    PubMed

    Liu, Feng; Haynes, Kenneth F; Appel, Arthur G; Liu, Nannan

    2014-06-01

    Populations of the common bed bug Cimex lectularius (Hemiptera; Cimicidae), a temporary ectoparasite on both humans and animals, have surged in many developed countries. Similar to other haematophagous arthropods, C. lectularius relies on its olfactory system to detect semiochemicals in the environment, including both attractants and repellents. To elucidate the olfactory responses of the common bed bug to commonly used insect chemical repellents, particularly haematophagous repellents, we investigated the neuronal responses of individual olfactory sensilla in C. lectularius' antennae to 52 insect chemical repellents, both synthetic and botanic. Different types of sensilla displayed highly distinctive response profiles. While C sensilla did not respond to any of the insect chemical repellents, Dγ sensilla proved to be the most sensitive in response to terpene-derived insect chemical repellents. Different chemical repellents elicited neuronal responses with differing temporal characteristics, and the responses of the olfactory sensilla to the insect chemical repellents were dose-dependent, with an olfactory response to the terpene-derived chemical repellent, but not to the non-terpene-derived chemical repellents. Overall, this study furnishes a comprehensive map of the olfactory response of bed bugs to commonly used insect chemical repellents, providing useful information for those developing new agents (attractants or repellents) for bed bug control.

  14. Mice with a "monoclonal nose": perturbations in an olfactory map impair odor discrimination.

    PubMed

    Fleischmann, Alexander; Shykind, Benjamin M; Sosulski, Dara L; Franks, Kevin M; Glinka, Meredith E; Mei, Dan Feng; Sun, Yonghua; Kirkland, Jennifer; Mendelsohn, Monica; Albers, Mark W; Axel, Richard

    2008-12-26

    We have altered the neural representation of odors in the brain by generating a mouse with a "monoclonal nose" in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced 20-fold. We observe that these mice can smell, but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

  15. Clinical features of olfactory disorders in patients seeking medical consultation

    PubMed Central

    Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

    2013-01-01

    Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

  16. Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.

    PubMed

    Jenkins, Paul M; Hurd, Toby W; Zhang, Lian; McEwen, Dyke P; Brown, R Lane; Margolis, Ben; Verhey, Kristen J; Martens, Jeffrey R

    2006-06-20

    Nonmotile cilia on olfactory sensory neurons (OSNs) compartmentalize signaling molecules, including odorant receptors and cyclic nucleotide-gated (CNG) channels, allowing for efficient, spatially confined responses to sensory stimuli . Little is known about the mechanisms of the ciliary targeting of olfactory CNG channels, composed of three subunits: CNGA2, CNGA4, and CNGB1b . Recent reports suggest that subunit composition of the retinal CNG channel influences localization, leading to disease . However, the mechanistic role of subunits in properly targeting native olfactory CNG channels remains unclear. Here, we show that heteromeric assembly with CNGB1b, containing a critical carboxy-terminal motif (RVxP), is required for ciliary trafficking of olfactory CNG channels. Movement of proteins within the cilia is governed by intraflagellar transport (IFT), a process that facilitates bidirectional movement of cargo along microtubules. Work in C. elegans has established that heterotrimeric and homodimeric kinesin-2 family members play a critical role in anterograde transport . In mammalian systems, the heterotrimeric KIF3a/KIF3b/KAP-3 complex plays a clear role in IFT; however, no role has been established for KIF17, the mammalian homolog of OSM-3 . Here, we demonstrate that KIF17 is required for olfactory CNG channel targeting, providing novel insights into mechanisms of mammalian ciliary transport.

  17. A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

    PubMed Central

    Bernhard, Nirit; van der Kooy, Derek

    2000-01-01

    Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

  18. The olfactory receptor gene repertoires in secondary-adapted marine vertebrates: evidence for reduction of the functional proportions in cetaceans.

    PubMed

    Kishida, Takushi; Kubota, Shin; Shirayama, Yoshihisa; Fukami, Hironobu

    2007-08-22

    An olfactory receptor (OR) multigene family is responsible for the well-developed sense of smell possessed by terrestrial tetrapods. Mammalian OR genes had diverged greatly in the terrestrial environment after the fish-tetrapod split, indicating their importance to land habitation. In this study, we analysed OR genes of marine tetrapods (minke whale Balaenoptera acutorostrata, dwarf sperm whale Kogia sima, Dall's porpoise Phocoenoides dalli, Steller's sea lion Eumetopias jubatus and loggerhead sea turtle Caretta caretta) and revealed that the pseudogene proportions of OR gene repertoires in whales were significantly higher than those in their terrestrial relative cattle and also in sea lion and sea turtle. On the other hand, the pseudogene proportion of OR sequences in sea lion was not significantly higher compared with that in their terrestrial relative (dog). It indicates that secondary perfectly adapted marine vertebrates (cetaceans) have lost large amount of their OR genes, whereas secondary-semi-adapted marine vertebrates (sea lions and sea turtles) still have maintained their OR genes, reflecting the importance of terrestrial environment for these animals.

  19. Structure and diversity in mammalian accessory olfactory bulb.

    PubMed

    Meisami, E; Bhatnagar, K P

    1998-12-15

    The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of

  20. Odor-induced phosphorylation of olfactory cilia proteins.

    PubMed Central

    Boekhoff, I; Schleicher, S; Strotmann, J; Breer, H

    1992-01-01

    Stimulation of isolated rat olfactory cilia in the presence of [gamma-32P]ATP leads to a significantly enhanced incorporation of [32P]phosphate. Depending on the type of odorants applied, the induced phosphorylation is completely blocked by specific inhibitors of either protein kinase A or protein kinase C. Time-course experiments indicate that the odor-induced modification of ciliary proteins is transient; the intensity of labeling decayed over time (1-10 sec). Separation of ciliary proteins by SDS/polyacrylamide gel electrophoresis followed by autoradiography demonstrated that upon stimulation with lilial, a single polypeptide (50,000 Da) was phosphorylated; the size of the modified protein is in line with the hypothesis that odorant receptors are phosphorylated subsequent to activation by specific odors. Images PMID:1334554

  1. ATP Mediates Neuroprotective and Neuroproliferative Effects in Mouse Olfactory Epithelium following Exposure to Satratoxin G In Vitro and In Vivo

    PubMed Central

    Jia, Cuihong; Sangsiri, Sutheera; Belock, Bethany; Iqbal, Tania R.; Pestka, James J.; Hegg, Colleen C.

    2011-01-01

    Intranasal aspiration of satratoxin G (SG), a mycotoxin produced by the black mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) in mouse olfactory epithelium (OE) through unknown mechanisms. Here, we show a dose-dependent induction of apoptosis 24 h post-SG exposure in vitro as measured by increased activated caspases in the OP6 olfactory placodal cell line and increased propidium iodide staining in primary OE cell cultures. Intranasal aspiration of SG increased TUNEL (Terminal dUTP Nick End Labeling) staining in the neuronal layer of the OE and significantly increased the latency to find a buried food pellet, confirming that SG selectively induces neuronal apoptosis and demonstrating that SG impairs the sense of smell. Next, we investigated whether ATP can prevent SG-induced OE toxicity. ATP did not decrease apoptosis under physiological conditions but significantly reduced SG-induced OSN apoptosis in vivo and in vitro. Furthermore, purinergic receptor inhibition significantly increased apoptosis in OE primary cell culture and in vivo. These data indicate that ATP is neuroprotective against SG-induced OE toxicity. The number of cells that incorporated 5′-bromodeoxyuridine, a measure of proliferation, was significantly increased 3 and 6 days post-SG aspiration. Treatment with purinergic receptor antagonists significantly reduced SG-induced cell proliferation, whereas post-treatment with ATP significantly potentiated SG-induced cell proliferation. These data indicate that ATP is released and promotes cell proliferation via activation of purinergic receptors in SG-induced OE injury. Thus, the purinergic system is a therapeutic target to alleviate or restore the loss of OSNs. PMID:21865290

  2. Cladistic Analysis of Olfactory and Vomeronasal Systems

    PubMed Central

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2010-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses. PMID:21290004

  3. Cladistic analysis of olfactory and vomeronasal systems.

    PubMed

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2011-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies' view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical "cortex." We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

  4. Muscarinic Receptors Modulate Dendrodendritic Inhibitory Synapses to Sculpt Glomerular Output

    PubMed Central

    Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus

    2015-01-01

    Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. PMID:25855181

  5. Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

    PubMed

    Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

    2015-04-08

    Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

  6. Non-conventional solvents in liquid phase microextraction and aqueous biphasic systems.

    PubMed

    An, Jiwoo; Trujillo-Rodríguez, María J; Pino, Verónica; Anderson, Jared L

    2017-06-02

    The development of rapid, convenient, and high throughput sample preparation approaches such as liquid phase microextraction techniques have been continuously developed over the last decade. More recently, significant attention has been given to the replacement of conventional organic solvents used in liquid phase microextraction techniques in order to reduce toxic waste and to improve selectivity and/or extraction efficiency. With these objectives, non-conventional solvents have been explored in liquid phase microextraction and aqueous biphasic systems. The utilized non-conventional solvents include ionic liquids, magnetic ionic liquids, and deep eutectic solvents. They have been widely used as extraction solvents or additives in various liquid phase microextraction modes including dispersive liquid-liquid microextraction, single-drop microextraction, hollow fiber-liquid phase microextraction, as well as in aqueous biphasic systems. This review provides an overview into the use of non-conventional solvents in these microextraction techniques in the past 5 years (2012-2016). Analytical applications of the techniques are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Early Stage olfactory neuroblastoma and the impact of resecting dura and olfactory bulb.

    PubMed

    Mays, Ashley C; Bell, Diana; Ferrarotto, Renata; Phan, Jack; Roberts, Dianna; Fuller, Clifton D; Frank, Steven J; Raza, Shaan M; Kupferman, Michael E; DeMonte, Franco; Hanna, Ehab Y; Su, Shirley Y

    2018-06-01

    Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. 4. Laryngoscope, 128:1274-1280, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Contribution of pheromones processed by the main olfactory system to mate recognition in female mammals

    PubMed Central

    Baum, Michael J.

    2012-01-01

    Until recently it was widely believed that the ability of female mammals (with the likely exception of women) to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female's vomeronasal organ (VNO) and their subsequent processing by a neural circuit that includes the accessory olfactory bulb (AOB), vomeronasal amygdala, and hypothalamus. Emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the main olfactory epithelium (MOE) of female mice which, in turn, leads to the activation of a population of glomeruli and abutting mitral cells in the main olfactory bulb (MOB). Anatomical results along with functional neuroanatomical data demonstrate that some of these MOB mitral cells project to the vomeronasal amygdala. These particular MOB mitral cells were selectively activated (i.e., expressed Fos protein) by exposure to male as opposed to female urinary volatiles. A similar selectivity to opposite sex urinary volatiles was also seen in mitral cells of the AOB of female mice. Behavioral data from female mouse, ferret, and human are reviewed that implicate the main olfactory system, in some cases interacting with the accessory olfactory system, in mate recognition. PMID:22679420

  9. Candidate pheromone receptors of codling moth Cydia pomonella respond to pheromones and kairomones

    PubMed Central

    Cattaneo, Alberto Maria; Gonzalez, Francisco; Bengtsson, Jonas M.; Corey, Elizabeth A.; Jacquin-Joly, Emmanuelle; Montagné, Nicolas; Salvagnin, Umberto; Walker, William B.; Witzgall, Peter; Anfora, Gianfranco; Bobkov, Yuriy V.

    2017-01-01

    Olfaction plays a dominant role in the mate-finding and host selection behaviours of the codling moth (Cydia pomonella), an important pest of apple, pear and walnut orchards worldwide. Antennal transcriptome analysis revealed a number of abundantly expressed genes related to the moth olfactory system, including those encoding the olfactory receptors (ORs) CpomOR1, CpomOR3 and CpomOR6a, which belong to the pheromone receptor (PR) lineage, and the co-receptor (CpomOrco). Using heterologous expression, in both Drosophila olfactory sensory neurones and in human embryonic kidney cells, together with electrophysiological recordings and calcium imaging, we characterize the basic physiological and pharmacological properties of these receptors and demonstrate that they form functional ionotropic receptor channels. Both the homomeric CpomOrco and heteromeric CpomOrco + OR complexes can be activated by the common Orco agonists VUAA1 and VUAA3, as well as inhibited by the common Orco antagonists amiloride derivatives. CpomOR3 responds to the plant volatile compound pear ester ethyl-(E,Z)-2,4-decadienoate, while CpomOR6a responds to the strong pheromone antagonist codlemone acetate (E,E)-8,10-dodecadien-1-yl acetate. These findings represent important breakthroughs in the deorphanization of codling moth pheromone receptors, as well as more broadly into insect ecology and evolution and, consequently, for the development of sustainable pest control strategies based on manipulating chemosensory communication. PMID:28117454

  10. Meta-diamide insecticides acting on distinct sites of RDL GABA receptor from those for conventional noncompetitive antagonists.

    PubMed

    Nakao, Toshifumi; Banba, Shinich; Nomura, Michikazu; Hirase, Kangetsu

    2013-04-01

    The RDL GABA receptor is an attractive target of insecticides. Here we demonstrate that meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor antagonists showing high insecticidal activity against Spodoptera litura. We also suggest that the mode of action of the meta-diamides is distinct from that of conventional noncompetitive antagonists (NCAs), such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. Using a membrane potential assay, we examined the effects of the meta-diamide 3-benzamido-N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide (meta-diamide 7) and NCAs on mutant Drosophila RDL GABA receptors expressed in Drosophila Mel-2 cells. NCAs had little or no inhibitory activity against at least one of the three mutant receptors (A2'S, A2'G, and A2'N), which were reported to confer resistance to NCAs. In contrast, meta-diamide 7 inhibited all three A2' mutant receptors, at levels comparable to its activity with the wild-type receptor. Furthermore, the A2'S·T6'V mutation almost abolished the inhibitory effects of all NCAs. However, meta-diamide 7 inhibited the A2'S・T6'S mutant receptor at the same level as its activity with the wild-type receptor. In contrast, a G336M mutation in the third transmembrane domain of the RDL GABA receptor abolished the inhibitory activities of meta-diamide 7, although the G336M mutation had little effect on the inhibitory activities of conventional NCAs. Molecular modeling studies also suggested that the binding site of meta-diamides was different from those of NCAs. Meta-diamide insecticides are expected to be prominent insecticides effective against A2' mutant RDL GABA receptors with a different mode of action. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

    PubMed Central

    Turetsky, Bruce I.; Hahn, Chang-Gyu; Borgmann-Winter, Karin; Moberg, Paul J.

    2009-01-01

    Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that underlie disease-related cognitive and emotional disturbances. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indicator of schizophrenia pathology and may even serve as an “early warning” sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Convergent data indicate that structural and functional abnormalities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypothesis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers. PMID:19793796

  12. Odorant receptors directly activate phospholipase C/inositol-1,4,5-trisphosphate coupled to calcium influx in Odora cells.

    PubMed

    Liu, Guang; Badeau, Robert M; Tanimura, Akihiko; Talamo, Barbara R

    2006-03-01

    Mechanisms by which odorants activate signaling pathways in addition to cAMP are hard to evaluate in heterogeneous mixtures of primary olfactory neurons. We used single cell calcium imaging to analyze the response to odorant through odorant receptor (OR) U131 in the olfactory epithelial cell line Odora (Murrell and Hunter 1999), a model system with endogenous olfactory signaling pathways. Because adenylyl cyclase levels are low, agents activating cAMP formation do not elevate calcium, thus unmasking independent signaling mediated by OR via phospholipase C (PLC), inositol-1,4,5-trisphosphate (IP(3)), and its receptor. Unexpectedly, we found that extracellular calcium is required for odor-induced calcium elevation without the release of intracellular calcium, even though the latter pathway is intact and can be stimulated by ATP. Relevant signaling components of the PLC pathway and G protein isoforms are identified by western blot in Odora cells as well as in olfactory sensory neurons (OSNs), where they are localized to the ciliary zone or cell bodies and axons of OSNs by immunohistochemistry. Biotinylation studies establish that IP(3) receptors type 2 and 3 are at the cell surface in Odora cells. Thus, individual ORs are capable of elevating calcium through pathways not directly mediated by cAMP and this may provide another avenue for odorant signaling in the olfactory system.

  13. Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis.

    PubMed

    Apter, A J; Gent, J F; Frank, M E

    1999-09-01

    To characterize the relationship between allergic rhinitis, the severity and duration of nasal disease, olfactory function, and self-reported olfactory symptoms, including fluctuations or distortions in odor perception. Assessment of olfactory function and symptoms of 90 patients with allergic rhinitis. A clinic of a university teaching hospital and research facility. Sixty patients who presented to the Taste and Smell Clinic who had positive allergy test results and 30 patients who presented to the Allergy-Immunology Clinic. The Taste and Smell Clinic patients were grouped by nasal-sinus disease status (30 without chronic rhinosinusitis or nasal polyps, 14 with chronic rhinosinusitis but without polyps, and 16 with nasal polyps). Subjective olfactory symptom questionnaire and objective olfactory function tests. The Allergy-Immunology Clinic patients were diagnosed as being normosmic and the Taste and Smell Clinic patients as being hyposmic or anosmic with olfactory loss that increased significantly with nasal-sinus disease severity. Comparisons with normative data confirm that olfactory scores observed in all groups were significantly lower than expected because of the aging process alone. The self-reported duration of olfactory loss increased significantly with nasal-sinus disease severity. The Taste and Smell Clinic patients without chronic rhinosinusitis or nasal polyps reported the greatest incidence of olfactory distortions and olfactory loss associated with upper respiratory tract infections. There appears to be a continuum of duration and severity of olfactory loss in allergic rhinitis that parallels increasing severity of nasal-sinus disease. As a result of the increased frequency of respiratory infection associated with allergic rhinitis, these patients are at risk for damage to the olfactory epithelium.

  14. Methods to measure olfactory behavior in mice

    PubMed Central

    Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Lu, Song; Xia, Zhengui

    2015-01-01

    Mice rely on the sense of olfaction to detect food sources, recognize social and mating partners, and avoid predators. Many behaviors of mice including learning and memory, social interaction, fear, and anxiety are closely associated with their function of olfaction, and behavior tasks designed to evaluate those brain functions may use odors as cues. Accurate assessment of olfaction is not only essential for the study of olfactory system but also critical for proper interpretation of various mouse behaviors especially learning and memory, emotionality and affect, and sociality. Here we describe a series of behavior experiments that offer multidimensional and quantitative assessments for mouse’s olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, to both social and nonsocial odors. PMID:25645244

  15. Hypothalamus-Olfactory System Crosstalk: Orexin A Immunostaining in Mice

    PubMed Central

    Gascuel, Jean; Lemoine, Aleth; Rigault, Caroline; Datiche, Frédérique; Benani, Alexandre; Penicaud, Luc; Lopez-Mascaraque, Laura

    2012-01-01

    It is well known that olfaction influences food intake, and conversely, that an individual’s nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway. In rats, orexin positive cells are concentrated strictly in the lateral hypothalamus, while their projections invade nearly the entire brain including the olfactory system. Therefore, orexin appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways. So far, orexin has been described in rats, however, there is still a lack of information concerning its expression in the brains of adult and developing mice. In this context, we revisited the orexin A pattern in adult and developing mice using immunohistological methods and confocal microscopy. Besides minor differences, orexin A immunostaining in mice shares many features with those observed in rats. In the olfactory bulb, even though there are few orexin projections, they reach all the different layers of the olfactory bulb. In contrast to the presence of orexin projections in the main olfactory bulb, almost none have been found in the accessory olfactory bulb. The developmental expression of orexin A supports the hypothesis that orexin expression only appears post-natally. PMID:23162437

  16. Preservation of olfaction in surgery of olfactory groove meningiomas.

    PubMed

    Jang, Woo-Youl; Jung, Shin; Jung, Tae-Young; Moon, Kyung-Sub; Kim, In-Young

    2013-08-01

    Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of "Sniffin'Sticks" test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient's age, and gender were analyzed with attention to the post-operative olfactory function. Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size<4 cm and 42.3% in size>4 cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). If the tumor was smaller than 4 cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Effect of strong fragrance on olfactory detection threshold.

    PubMed

    Fasunla, Ayotunde James; Douglas, David Dayo; Adeosun, Aderemi Adeleke; Steinbach, Silke; Nwaorgu, Onyekwere George Benjamin

    2014-09-01

    To assess the olfactory threshold of healthy volunteers at the University College Hospital, Ibadan and to investigate the effect of perfume on their olfactory detection thresholds. A quasi-experimental study on olfactory detection thresholds of healthy volunteers from September 2013 to November 2013. Tertiary health institution. A structured questionniare was administered to the participants in order to obtain information on sociodemographics, occupation, ability to perceive smell, use of perfume, effects of perfume on appetite and self-confidence, history of allergy, and previous nasal surgery. Participants subjectively rated their olfactory performance. Subsequently, they had olfactory detection threshold testing done at baseline and after exposure to perfume with varied concentrations of n-butanol in a forced triple response and staircase fashion. Healthy volunteers, 37 males and 63 females, were evaluated. Their ages ranged from 19 to 59 years with a mean of 31 years ± 8. Subjectively, 94% of the participants had excellent olfactory function. In the pre-exposure forced triple response, 88% were able to detect the odor at ≤.25 mmol/l concentration while in the post-exposure forced triple response, only 66% were able to detect the odor at ≤.25 mmol/l concentration. There is also a statistical significant difference in the olfactory detection threshold score between the pre-exposure and post-exposure period in the participants (P < .05). Use of strong fragrances affects the olfactory detection threshold. Therefore patients and clinicians should be aware of this and its effects on the outcome of test of olfaction. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  18. Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.

    PubMed

    Song, Yijun; Cygnar, Katherine D; Sagdullaev, Botir; Valley, Matthew; Hirsh, Sarah; Stephan, Aaron; Reisert, Johannes; Zhao, Haiqing

    2008-05-08

    Ca2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+-permeable ion channels. In olfactory sensory neurons (OSNs), such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and, consequently, reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses.

  19. Olfactory neurons express a unique glycosylated form of the neural cell adhesion molecule (N-CAM)

    PubMed Central

    1990-01-01

    mAb-based approaches were used to identify cell surface components involved in the development and function of the frog olfactory system. We describe here a 205-kD cell surface glycoprotein on olfactory receptor neurons that was detected with three mAbs: 9-OE, 5-OE, and 13- OE. mAb 9-OE immunoreactivity, unlike mAbs 5-OE and 13-OE, was restricted to only the axons and terminations of the primary sensory olfactory neurons in the frog nervous system. The 9-OE polypeptide(s) were immunoprecipitated and tested for cross-reactivity with known neural cell surface components including HNK-1, the cell adhesion molecule L1, and the neural cell adhesion molecule (N-CAM). These experiments revealed that 9-OE-reactive molecules were not L1 related but were a subset of the 200-kD isoforms of N-CAM. mAb 9-OE recognized epitopes associated with N-linked carbohydrate residues that were distinct from the polysialic acid chains present on the embryonic form of N-CAM. Moreover, 9-OE N-CAM was a heterogeneous population consisting of subsets both with and without the HNK-1 epitope. Thus, combined immunohistochemical and immunoprecipitation experiments have revealed a new glycosylated form of N-CAM unique to the olfactory system. The restricted spatial expression pattern of this N-CAM glycoform suggests a possible role in the unusual regenerative properties of this sensory system. PMID:2186048

  20. Nanoparticle transport across in vitro olfactory cell monolayers.

    PubMed

    Gartziandia, Oihane; Egusquiaguirre, Susana Patricia; Bianco, John; Pedraz, José Luis; Igartua, Manoli; Hernandez, Rosa Maria; Préat, Véronique; Beloqui, Ana

    2016-02-29

    Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism.

    PubMed

    Salihoglu, Murat; Kurt, Onuralp; Ay, Seyid Ahmet; Baskoy, Kamil; Altundag, Aytug; Saglam, Muzaffer; Deniz, Ferhat; Tekeli, Hakan; Yonem, Arif; Hummel, Thomas

    2017-08-24

    Idiopathic hypogonadotrophic hypogonadism (IHH) with an olfactory deficit is defined as Kallmann syndrome (KS) and is distinct from normosmic IHH. Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with IHH. This case-control study included 31 controls and 45 IHH patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume (OBV) measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic IHH (aIHH), hyposmic IHH (hIHH) and normosmic IHH (nIHH). Discrimination, identification and threshold scores of patients with KS were significantly lower than controls. Threshold scores of patients with nIHH were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the aIHH group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic IHH groups and controls. OBV was lower bilaterally in all patient groups when compared with controls. The OBV of both sides was found to be significantly correlated with TDI scores in IHH patients. 1) There were no significant differences in gustatory function between controls and IHH patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the HH group. The current results indicate a continuum from anosmia to normosmia in IHH patients. Copyright © 2017

  2. Olfactory Deficit Detected by fMRI in Early Alzheimer’s Disease

    PubMed Central

    Wang, Jianli; Eslinger, Paul J.; Doty, Richard L.; Zimmerman, Erin K.; Grunfeld, Robert; Sun, Xiaoyu; Connor, James R.; Price, Joseph L.; Smith, Michael B.; Yang, Qing X.

    2012-01-01

    Alzheimer’s disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, twelve early stage AD patients and thirteen non-demented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The Blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and functional cognitive decline. PMID:20709038

  3. [Deficits in medical counseling in olfactory dysfunction].

    PubMed

    Haxel, B R; Nisius, A; Fruth, K; Mann, W J; Muttray, A

    2012-05-01

    Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

  4. Evaluation of the effect of cigarette smoking on the olfactory neuroepithelium of New Zealand white rabbit, using scanning electron microscope.

    PubMed

    Iskander, Nagi M; El-Hennawi, Diaa M; Yousef, Tarek F; El-Tabbakh, Mohammed T; Elnahriry, Tarek A

    2017-06-01

    To detect ultra-structural changes of Rabbit's olfactory neuro-epithelium using scanning electron microscope after exposure to cigarette smoking. Sixty six rabbits (Pathogen free New Zealand white rabbits weighing 1-1.5 kg included in the study were randomly assigned into one of three groups: control group did not expose to cigarette smoking, study group 1 was exposed to cigarette smoking for 3 months and study group 2 was exposed to cigarette smoking 3 months and then stopped for 2 months. Olfactory neuro-epithelium from all rabbits were dissected and examined under Philips XL-30 scanning electron microscope. Changes that were found in the rabbits of study group 1 in comparison to control group were loss of microvilli of sustentacular cells (p = 0.016) and decreases in distribution of specialized cilia of olfactory receptor cells (p = 0.046). Also respiratory metaplasia was detected. These changes were reversible in study group 2. Cigarette smoking causes ultra-structural changes in olfactory neuro-epithelium which may explain why smell was affected in cigarette smokers. Most of these changes were reversible after 45 days of cessation of cigarette smoking to the rabbits.

  5. Sensational placodes: Neurogenesis in the otic and olfactory systems

    PubMed Central

    Maier, Esther C.; Saxena, Ankur; Alsina, Berta; Bronner, Marianne E.; Whitfield, Tanya T.

    2014-01-01

    For both the intricate morphogenetic layout of the sensory cells in the ear and the elegantly radial arrangement of the sensory neurons in the nose, numerous signaling molecules and genetic determinants are required in concert to generate these specialized neuronal populations that help connect us to our environment. In this review, we outline many of the proteins and pathways that play essential roles in the differentiation of otic and olfactory neurons and their integration into their non-neuronal support structures. In both cases, well-known signaling pathways together with region-specific factors transform thickened ectodermal placodes into complex sense organs containing numerous, diverse neuronal subtypes. Olfactory and otic placodes, in combination with migratory neural crest stem cells, generate highly specialized subtypes of neuronal cells that sense sound, position and movement in space, odors and pheromones throughout our lives. PMID:24508480

  6. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

    PubMed

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  7. Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

    PubMed Central

    Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

    2013-01-01

    Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

  8. Luteinizing hormone-releasing hormone (LHRH) in rat olfactory systems.

    PubMed

    Witkin, J W; Silverman, A J

    1983-08-20

    The luteinizing hormone-releasing hormone (LHRH) systems of rat olfactory bulbs and nasal areas were studied in neonatal and adult rats. Animals were perfused with Zamboni's fixative and olfactory bulbs with nasal olfactory areas intact were removed, postfixed, and decalcified. LHRH was immunohistochemically demonstrated in unembedded frozen or vibratome sections. Luteinizing hormone-releasing hormone immunoreactive elements were found along the course of the nervus terminalis (NT) and within both the main and accessory olfactory bulbs (MOB and AOB, respectively). Both LHRH neurons and fibers were present in the AOB, but only fibers were detected in the MOB. The fibers of the AOB were not confined to any particular lamina while fibers in the MOB were found mainly in the external plexiform layer. LHRH fibers were found in the mucosa of the olfactory epithelium of the vomeronasal organ in both neonatal and adult rats. The NT probably serves as a source of LHRH fibers for both the AOB and the MOB and for fibers observed in the olfactory epithelium of the vomeronasal organ. Other likely sources of LHRH fibers in the olfactory bulb are discussed.

  9. Evaluation of olfactory function in adults with primary hypothyroidism.

    PubMed

    Günbey, Emre; Karlı, Rıfat; Gökosmanoğlu, Feyzi; Düzgün, Berkan; Ayhan, Emre; Atmaca, Hulusi; Ünal, Recep

    2015-10-01

    Sufficient clinical data are not available on the effect of hypothyroidism on olfactory function in adults. In this study, we aimed to evaluate the olfactory function of adult patients diagnosed with primary hypothyroidism. Forty-five patients aged between 18 and 60 years who were diagnosed with clinical primary hypothyroidism and 45 healthy controls who had normal thyroid function tests were included in the study. Sniffin' Sticks olfactory test results of the 2 groups were compared. The relationships between thyroid function tests and olfactory parameters were evaluated. Odor threshold, identification, and discrimination scores of the hypothyroid group were significantly lower than those of the control group (p < 0.001). A significant positive correlation was detected between free triiodothyronine (FT3) levels and odor threshold, identification, and discrimination scores (p < 0.001). There was no significant relationship between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and olfactory parameters. Our study revealed diminished olfactory function in adults with hypothyroidism. FT3 levels were found to have a more significant relationship with olfactory parameters than TSH or FT4 levels. © 2015 ARS-AAOA, LLC.

  10. Olfactory function in psychotic disorders: Insights from neuroimaging studies

    PubMed Central

    Good, Kimberley P; Sullivan, Randii Lynn

    2015-01-01

    Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

  11. Distinct molecular underpinnings of Drosophila olfactory trace conditioning

    PubMed Central

    Shuai, Yichun; Hu, Ying; Qin, Hongtao; Campbell, Robert A. A.; Zhong, Yi

    2011-01-01

    Trace conditioning is valued as a simple experimental model to assess how the brain associates events that are discrete in time. Here, we adapted an olfactory trace conditioning procedure in Drosophila melanogaster by training fruit flies to avoid an odor that is followed by foot shock many seconds later. The molecular underpinnings of the learning are distinct from the well-characterized simultaneous conditioning, where odor and punishment temporally overlap. First, Rutabaga adenylyl cyclase (Rut-AC), a putative molecular coincidence detector vital for simultaneous conditioning, is dispensable in trace conditioning. Second, dominant-negative Rac expression, thought to sustain early labile memory, significantly enhances learning of trace conditioning, but leaves simultaneous conditioning unaffected. We further show that targeting Rac inhibition to the mushroom body (MB) but not the antennal lobe (AL) suffices to achieve the enhancement effect. Moreover, the absence of trace conditioning learning in D1 dopamine receptor mutants is rescued by restoration of expression specifically in the adult MB. These results suggest the MB as a crucial neuroanatomical locus for trace conditioning, which may harbor a Rac activity-sensitive olfactory “sensory buffer” that later converges with the punishment signal carried by dopamine signaling. The distinct molecular signature of trace conditioning revealed here shall contribute to the understanding of how the brain overcomes a temporal gap in potentially related events. PMID:22123966

  12. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    ERIC Educational Resources Information Center

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  13. Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells

    PubMed Central

    SAMARI, NADA; DE SAINT-GEORGES, LOUIS; PANI, GIUSEPPE; BAATOUT, SARAH; LEYNS, LUC; BENOTMANE, MOHAMMED ABDERRAFI

    2013-01-01

    During cortical development, N-methyl D-aspartate (NMDA) receptors are highly involved in neuronal maturation and synapse establishment. Their implication in the phenomenon of excitotoxicity has been extensively described in several neurodegenerative diseases due to the permissive entry of Ca2+ ions and massive accumulation in the intracellular compartment, which is highly toxic to cells. Ionising radiation is also a source of stress to the cells, particularly immature neurons. Their capacity to induce cell death has been described for various cell types either by directly damaging the DNA or indirectly through the generation of reactive oxygen species responsible for the activation of a battery of stress response effectors leading in certain cases, to cell death. In this study, in order to determine whether a link exists between NMDA receptors-mediated excitotoxicity and radiation-induced cell death, we evaluated radiation-induced cell death in vitro and in vivo in maturing neurons during the fetal period. Cell death induction was assessed by TUNEL, caspase-3 activity and DNA ladder assays, with or without the administration of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist which blocks neuronal Ca2+ influx. To further investigate the possible involvement of Ca2+-dependent enzyme activation, known to occur at high Ca2+ concentrations, we examined the protective effect of a calpain inhibitor on cell death induced by radiation. Doses ranging from 0.2 to 0.6 Gy of X-rays elicited a clear apoptotic response that was prevented by the injection of dizocilpine (MK-801) or calpain inhibitor. These data demonstrate the involvement of NMDA receptors in radiation-induced neuronal death by the activation of downstream effectors, including calpain-related pathways. An increased apoptotic process elicited by radiation, occurring independently of the normal developmental scheme, may eliminate post-mitotic but immature neuronal cells and deeply impair the

  14. An Olfactory Indicator for Acid-Base Titrations.

    ERIC Educational Resources Information Center

    Flair, Mark N.; Setzer, William N.

    1990-01-01

    The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

  15. Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury

    PubMed Central

    Wang, Lu; Espinoza, Herbert M.; MacDonald, James W.; Bammler, Theo K.; Williams, Chase R.; Yeh, Andrew; Louie, Ke’ale W.; Marcinek, David J.; Gallagher, Evan P.

    2016-01-01

    Pacific salmon exposed to sublethal concentrations of organophosphate pesticides (OP) have impaired olfactory function that can lead to loss of behaviors that are essential for survival. These exposures often involve mixtures and can occur at levels below those which inhibit acetylcholinesterase (AChE). In this study, juvenile Coho salmon were exposed for 24 h to either 0.1, 0.5, or 2.5 ppb chlorpyrifos (CPF), 2, 10, or 50 ppb malathion (MAL), or binary mixtures of 0.1 CPF:2 ppb MAL, 0.5 CPF:10 ppb MAL, or 2.5 CPF:10 ppb MAL to mimic single and binary environmental exposures. Microarray analysis of olfactory rosettes from pesticide-exposed salmon revealed differentially expressed genes involved in nervous system function and signaling, aryl hydrocarbon receptor signaling, xenobiotic metabolism, and mitochondrial dysfunction. Coho exposed to OP mixtures exhibited a more pronounced loss in detection of a predatory olfactory cue relative to those exposed to single compounds, whereas respirometry experiments demonstrated that exposure to OPs, individually and in mixtures, reduced maximum respiratory capacity of olfactory rosette mitochondria. The observed molecular, biochemical, and behavioral effects occurred largely in the absence of effects on brain AChE. In summary, our results provide new insights associated with the sublethal neurotoxic effects of OP mixtures relevant to environmental exposures involving molecular and cellular pathways of injury to the salmon olfactory system that underlie neurobehavioral injury. PMID:26494550

  16. Non-Conventional Yeast Strains Increase the Aroma Complexity of Bread

    PubMed Central

    Rezaei, Mohammad Naser; Steensels, Jan; Courtin, Christophe M.; Verstrepen, Kevin J.

    2016-01-01

    Saccharomyces cerevisiae is routinely used yeast in food fermentations because it combines several key traits, including fermentation efficiency and production of desirable flavors. However, the dominance of S. cerevisiae in industrial fermentations limits the diversity in the aroma profiles of the end products. Hence, there is a growing interest in non-conventional yeast strains that can help generate the diversity and complexity desired in today’s diversified and consumer-driven markets. Here, we selected a set of non-conventional yeast strains to examine their potential for bread fermentation. Here, we tested ten non-conventional yeasts for bread fermentation, including two Saccharomyces species that are not currently used in bread making and 8 non-Saccharomyces strains. The results show that Torulaspora delbrueckii and Saccharomyces bayanus combine satisfactory dough fermentation with an interesting flavor profile. Sensory analysis and HS-SPME-GC-MS analysis confirmed that these strains produce aroma profiles that are very different from that produced by a commercial bakery strain. Moreover, bread produced with these yeasts was preferred by a majority of a trained sensory panel. These results demonstrate the potential of T. delbrueckii and S. bayanus as alternative yeasts for bread dough leavening, and provide a general experimental framework for the evaluation of more yeasts and bacteria. PMID:27776154

  17. Non-Conventional Yeast Strains Increase the Aroma Complexity of Bread.

    PubMed

    Aslankoohi, Elham; Herrera-Malaver, Beatriz; Rezaei, Mohammad Naser; Steensels, Jan; Courtin, Christophe M; Verstrepen, Kevin J

    2016-01-01

    Saccharomyces cerevisiae is routinely used yeast in food fermentations because it combines several key traits, including fermentation efficiency and production of desirable flavors. However, the dominance of S. cerevisiae in industrial fermentations limits the diversity in the aroma profiles of the end products. Hence, there is a growing interest in non-conventional yeast strains that can help generate the diversity and complexity desired in today's diversified and consumer-driven markets. Here, we selected a set of non-conventional yeast strains to examine their potential for bread fermentation. Here, we tested ten non-conventional yeasts for bread fermentation, including two Saccharomyces species that are not currently used in bread making and 8 non-Saccharomyces strains. The results show that Torulaspora delbrueckii and Saccharomyces bayanus combine satisfactory dough fermentation with an interesting flavor profile. Sensory analysis and HS-SPME-GC-MS analysis confirmed that these strains produce aroma profiles that are very different from that produced by a commercial bakery strain. Moreover, bread produced with these yeasts was preferred by a majority of a trained sensory panel. These results demonstrate the potential of T. delbrueckii and S. bayanus as alternative yeasts for bread dough leavening, and provide a general experimental framework for the evaluation of more yeasts and bacteria.

  18. Antennal transcriptome analysis and comparison of olfactory genes in two sympatric defoliators, Dendrolimus houi and Dendrolimus kikuchii (Lepidoptera: Lasiocampidae).

    PubMed

    Zhang, Sufang; Zhang, Zhen; Wang, Hongbin; Kong, Xiangbo

    2014-09-01

    The Yunnan pine and Simao pine caterpillar moths, Dendrolimus houi Lajonquière and Dendrolimus kikuchii Matsumura (Lepidoptera: Lasiocampidae), are two closely related and sympatric pests of coniferous forests in southwestern China, and olfactory communication systems of these two insects have received considerable attention because of their economic importance. However, there is little information on the molecular aspect of odor detection about these insects. Furthermore, although lepidopteran species have been widely used in studies of insect olfaction, few work made comparison between sister moths on the olfactory recognition mechanisms. In this study, next-generation sequencing of the antennal transcriptome of these two moths were performed to identify the major olfactory genes. After comparing the antennal transcriptome of these two moths, we found that they exhibit highly similar transcripts-associated GO terms. Chemosensory gene families were further analyzed in both species. We identified 23 putative odorant binding proteins (OBP), 17 chemosensory proteins (CSP), two sensory neuron membrane proteins (SNMP), 33 odorant receptors (OR), and 10 ionotropic receptors (IR) in D. houi; and 27 putative OBPs, 17 CSPs, two SNMPs, 33 ORs, and nine IRs in D. kikuchii. All these transcripts were full-length or almost full-length. The predicted protein sequences were compared with orthologs in other species of Lepidoptera and model insects, including Bombyx mori, Manduca sexta, Heliothis virescens, Danaus plexippus, Sesamia inferens, Cydia pomonella, and Drosophila melanogaster. The sequence homologies of the orthologous genes in D. houi and D. kikuchii are very high. Furthermore, the olfactory genes were classed according to their expression level, and the highly expressed genes are our target for further function investigation. Interestingly, many highly expressed genes are ortholog gene of D. houi and D. kikuchii. We also found that the Classic OBPs were

  19. Just follow your nose: homing by olfactory cues in ants.

    PubMed

    Steck, Kathrin

    2012-04-01

    How is an ant-equipped with a brain that barely exceeds the size of a pinhead-capable of achieving navigational marvels? Even though evidences suggest that navigation is a multimodal process, ants heavily depend on olfactory cues-of pheromonal and non-pheromonal nature-for foraging and orientation. Recent studies have directed their attention to the efficiency of pheromone trail networks. Advances in neurophysiological techniques make it possible to investigate trail pheromone processing in the ant's brain. In addition to relying on pheromone odours, ants also make use of volatiles emanating from the nest surroundings. Deposited in the vicinity of the nest, these home-range markings help the ants to home after a foraging run. Furthermore, olfactory landmarks associated with the nest enhance ants' homing abilities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. No evidence for visual context-dependency of olfactory learning in Drosophila

    NASA Astrophysics Data System (ADS)

    Yarali, Ayse; Mayerle, Moritz; Nawroth, Christian; Gerber, Bertram

    2008-08-01

    How is behaviour organised across sensory modalities? Specifically, we ask concerning the fruit fly Drosophila melanogaster how visual context affects olfactory learning and recall and whether information about visual context is getting integrated into olfactory memory. We find that changing visual context between training and test does not deteriorate olfactory memory scores, suggesting that these olfactory memories can drive behaviour despite a mismatch of visual context between training and test. Rather, both the establishment and the recall of olfactory memory are generally facilitated by light. In a follow-up experiment, we find no evidence for learning about combinations of odours and visual context as predictors for reinforcement even after explicit training in a so-called biconditional discrimination task. Thus, a ‘true’ interaction between visual and olfactory modalities is not evident; instead, light seems to influence olfactory learning and recall unspecifically, for example by altering motor activity, alertness or olfactory acuity.

  1. Heterogeneous distribution of G protein alpha subunits in the main olfactory and vomeronasal systems of Rhinella (Bufo) arenarum tadpoles.

    PubMed

    Jungblut, Lucas D; Paz, Dante A; López-Costa, Juan J; Pozzi, Andrea G

    2009-10-01

    We evaluated the presence of G protein subtypes Galpha(o), Galpha(i2), and Galpha(olf) in the main olfactory system (MOS) and accessory or vomeronasal system (VNS) of Rhinella (Bufo) arenarum tadpoles, and here describe the fine structure of the sensory cells in the olfactory epithelium (OE) and vomeronasal organ (VNO). The OE shows olfactory receptor neurons (ORNs) with cilia in the apical surface, and the vomeronasal receptor neurons (VRNs) of the VNO are covered with microvilli. Immunohistochemistry detected the presence of at least two segregated populations of ORNs throughout the OE, coupled to Galpha(olf) and Galpha(o). An antiserum against Galpha(i2) was ineffective in staining the ORNs. In the VNO, Galpha(o) neurons stained strongly but lacked immunoreactivity to any other Galpha subunit in all larval stages analyzed. Western blot analyses and preabsorption experiments confirmed the specificity of the commercial antisera used. The functional significance of the heterogeneous G-protein distribution in R. arenarum tadpoles is not clear, but the study of G- protein distributions in various amphibian species is important, since this vertebrate group played a key role in the evolution of tetrapods. A more complete knowledge of the amphibian MOS and VNS would help to understand the functional organization and evolution of vertebrate chemosensory systems. This work demonstrates, for the first time, the existence of a segregated distribution of G-proteins in the OE of R. arenarum tadpoles.

  2. Differential effects of unilateral olfactory deprivation on noradrenergic and cholinergic systems in the main olfactory bulb of the rat.

    PubMed

    Gómez, C; Briñón, J G; Colado, M I; Orio, L; Vidal, M; Barbado, M V; Alonso, J R

    2006-09-15

    The lack of environmental olfactory stimulation produced by sensory deprivation causes significant changes in the deprived olfactory bulb. Olfactory transmission in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems. The present report examines the effects of unilateral deprivation on the noradrenergic and cholinergic centrifugal systems innervating the MOB. The morphology, distribution, and density of positive axons were studied in the MOBs of control and deprived rats, using dopamine-beta-hydroxylase (DBH)-immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial sections. Catecholamine content was compared among the different groups of MOBs (control, contralateral, and ipsilateral to the deprivation) using high-performance liquid chromatography analysis. Sensory deprivation revealed that the noradrenergic system developed adaptive plastic changes after olfactory deprivation, including important modifications in its fiber density and distribution, while no differences in cholinergic innervation were observed under the same conditions. The noradrenergic system underwent an important alteration in the glomerular layer, in which some glomeruli showed a dense noradrenergic innervation that was not detected in control animals. The DBH-positive glomeruli with the highest noradrenergic fiber density were compared with AChE-stained sections and it was observed that the strongly noradrenergic-innervated glomeruli were always atypical glomeruli (characterized by their strong degree of cholinergic innervation). In addition to the morphological findings, our biochemical data revealed that olfactory deprivation caused a decrease in the content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ipsilateral MOB in comparison to the contralateral and control MOBs, together with an increase in noradrenaline levels in both the ipsilateral and contralateral MOBs. Our results show that regulation of the noradrenergic

  3. Expression of calmodulin mRNA in rat olfactory neuroepithelium.

    PubMed

    Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

    1991-04-01

    A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

  4. Olfactory Cued Learning Paradigm.

    PubMed

    Liu, Gary; McClard, Cynthia K; Tepe, Burak; Swanson, Jessica; Pekarek, Brandon; Panneerselvam, Sugi; Arenkiel, Benjamin R

    2017-05-05

    Sensory stimulation leads to structural changes within the CNS (Central Nervous System), thus providing the fundamental mechanism for learning and memory. The olfactory circuit offers a unique model for studying experience-dependent plasticity, partly due to a continuous supply of integrating adult born neurons. Our lab has recently implemented an olfactory cued learning paradigm in which specific odor pairs are coupled to either a reward or punishment to study downstream circuit changes. The following protocol outlines the basic set up for our learning paradigm. Here, we describe the equipment setup, programming of software, and method of behavioral training.

  5. Distribution of olfactory epithelium in the primate nasal cavity: are microsmia and macrosmia valid morphological concepts?

    PubMed

    Smith, Timothy D; Bhatnagar, Kunwar P; Tuladhar, Praphul; Burrows, Annie M

    2004-11-01

    The terms "microsmatic" and "macrosmatic" are used to compare species with greater versus lesser olfactory capabilities, such as carnivores compared to certain primates. These categories have been morphologically defined based on the size of olfactory bulb and surface area of olfactory epithelium in the nasal fossa. The present study examines assumptions regarding the morphological relationship of bony elements to the olfactory mucosa, the utility of olfactory epithelial surface area as a comparative measurement, and the utility of the microsmatic concept. We examined the distribution of olfactory neuroepithelium (OE) across the anteroposterior length of the nasal fossa (from the first completely enclosed cross-section of the nasal fossa to the choanae) in the microsmatic marmoset (Callithrix jacchus) compared to four species of nocturnal strepsirrhines (Otolemur crassicaudatus, O. garnetti, Microcebus murinus, and Cheirogaleus medius). Adults of all species were examined and infant C. jacchus, O. crassicaudatus, M. murinus, and C. medius were also examined. All specimens were serially sectioned in the coronal plane and prepared for light microscopic study. Distribution of OE across all the turbinals, nasal septal surfaces, and accessory spaces of the nasal chamber was recorded for each specimen. The right nasal fossae of one adult C. jacchus and one neonatal M. murinus were also three-dimensionally reconstructed using Scion Image software to reveal OE distribution. Findings showed OE to be distributed relatively more anteriorly in adult C. jacchus compared to strepsirrhines. It was also distributed more anteriorly along the nasal septal walls and recesses in neonates than adults. Our findings also showed that OE surface area was not a reliable proxy for receptor neuron numbers due to differing OE thickness among species. Such results indicate that nasal cavity morphology must be carefully reconsidered regarding traditional functional roles (olfaction versus air

  6. Identification and Differential Expression of a Candidate Sex Pheromone Receptor in Natural Populations of Spodoptera litura

    PubMed Central

    Lin, Xinda; Zhang, Qinhui; Wu, Zhongnan; Du, Yongjun

    2015-01-01

    Olfaction is primarily mediated by highly specific olfactory receptors (ORs), a subfamily of which are the pheromone receptors that play a key role in sexual communication and can contribute to reproductive isolation. Here we cloned and identified an olfactory receptor, SlituOR3 (Genbank NO. JN835270), from Spodoptera litura, to be the candidate pheromone receptor. It exhibited male-biased expression in the antennae, where they were localized at the base of sensilla trichoidea. Conserved orthologues of these receptors were found amongst known pheromone receptors within the Lepidoptera, and SlituOR3 were placed amongst a clade of candidate pheromone receptors in a phylogeny tree of insect ORs. SlituOR3 is required for the EAG responses to both Z9E11-14:OAc and Z9E12-14:OAc SlituOR3 showed differential expression in S. litura populations attracted to traps baited with a series of sex pheromone blends composed of different ratios of (9Z,11E)-tetradecadienyl acetate (Z9E11-14:OAc) and (9Z,12E)-tetradecadienyl acetate (Z9E12-14:OAc). The changes in the expression level of SlitOR3 and antennal responses after SlitOR3 silencing suggested that SlitOR3 is required for the sex pheromone signaling. We infer that variation in transcription levels of olfactory receptors may modulate sex pheromone perception in male moths and could affect both of pest control and monitoring efficiency by pheromone application after long time mass trapping with one particular ratio of blend in the field. PMID:26126192

  7. The Evaluation of Olfactory Function in Patients With Schizophrenia.

    PubMed

    Robabeh, Soleimani; Mohammad, Jalali Mir; Reza, Ahmadi; Mahan, Badri

    2015-04-23

    The aim of this study was to compare olfactory threshold, smell identification, intensity and pleasantness ratings between patients with schizophrenia and healthy controls, and (2) to evaluate correlations between ratings of olfactory probes and illness characteristics. Thirty one patients with schizophrenia and 31 control subjects were assessed with the olfactory n-butanol threshold test, the Iran smell identification test (Ir-SIT), and the suprathreshold amyl acetate odor intensity and odor pleasantness rating test. All olfactory tasks were performed unirhinally. Patients with schizophrenia showed disrupted olfaction in all four measures. Longer duration of schizophrenia was associated with a larger impairment of olfactory threshold or microsmic range on the Ir-SIT (P=0.04, P=0.05, respectively). In patients with schizophrenia, female subjects' ratings of pleasantness followed the same trend as control subjects, whereas male patients' ratings showed an opposite trend. Patients exhibiting high positive score on the positive and negative syndrome scale (PANSS) performed better on the olfactory threshold test (r=0.37, P=0.04). The higher odor pleasantness ratings of patients were associated with presence of positive symptoms. The results suggest that both male and female patients with schizophrenia had difficulties on the olfactory threshold and smell identification tests, but appraisal of odor pleasantness was more disrupted in male patients.

  8. Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

    PubMed

    Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

    2010-08-01

    Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

  9. The outcome of septorhinoplasty surgery on olfactory function.

    PubMed

    Randhawa, P S; Watson, N; Lechner, M; Ritchie, L; Choudhury, N; Andrews, P J

    2016-02-01

    To assess olfactory outcomes in patients undergoing septorhinoplasty surgery in our unit. Prospective cohort study. The Royal National Throat Nose and Ear Hospital, London. Forty-three patients undergoing functional septorhinoplasty (Males = 26; mean age = 34.1 ± 12.2) were recruited into the study. The primary outcome of olfactory function was assessed using 'Sniffin sticks'. Our secondary outcomes were assessment of patient quality of life using the disease specific Sino-nasal Outcome Test-23 questionnaire (SNOT-23) and a visual analogue scale for sense of smell. These measures were repeated at 12 weeks post operatively. There was a significant change in the Sniffin' sticks score post-operatively (8.3 versus 9.6; P < 0.001). The SNOT-23 score also showed a significant improvement post-operatively (53.5 versus 40.4; P < 0.001). A significant improvement was not found in the smell/taste question (question 21) of the SNOT-23 questionnaire as well as the visual analogue scale for sense of smell. A difference in olfactory outcome was not found between open versus closed approaches, primary versus revision surgery and traumatic versus non traumatic cases. The results show a measured significant improvement in olfaction following functional Septorhinoplasty but not a subjective improvement in the patients perception of their sense of smell and hence not a clinically significant difference. The reasons for the measured improvement are not clear and are likely to be multifactorial. © 2015 John Wiley & Sons Ltd.

  10. Olfactory epithelium influences the orientation of mitral cell dendrites during development.

    PubMed

    López-Mascaraque, Laura; García, Concepción; Blanchart, Albert; De Carlos, Juan A

    2005-02-01

    We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Copyright 2004 Wiley-Liss, Inc.

  11. Evolution of olfaction in non-avian theropod dinosaurs and birds

    PubMed Central

    Zelenitsky, Darla K.; Therrien, François; Ridgely, Ryan C.; McGee, Amanda R.; Witmer, Lawrence M.

    2011-01-01

    Little is known about the olfactory capabilities of extinct basal (non-neornithine) birds or the evolutionary changes in olfaction that occurred from non-avian theropods through modern birds. Although modern birds are known to have diverse olfactory capabilities, olfaction is generally considered to have declined during avian evolution as visual and vestibular sensory enhancements occurred in association with flight. To test the hypothesis that olfaction diminished through avian evolution, we assessed relative olfactory bulb size, here used as a neuroanatomical proxy for olfactory capabilities, in 157 species of non-avian theropods, fossil birds and living birds. We show that relative olfactory bulb size increased during non-avian maniraptoriform evolution, remained stable across the non-avian theropod/bird transition, and increased during basal bird and early neornithine evolution. From early neornithines through a major part of neornithine evolution, the relative size of the olfactory bulbs remained stable before decreasing in derived neoavian clades. Our results show that, rather than decreasing, the importance of olfaction actually increased during early bird evolution, representing a previously unrecognized sensory enhancement. The relatively larger olfactory bulbs of earliest neornithines, compared with those of basal birds, may have endowed neornithines with improved olfaction for more effective foraging or navigation skills, which in turn may have been a factor allowing them to survive the end-Cretaceous mass extinction. PMID:21490022

  12. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65

    PubMed Central

    Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K.; Zhu, Hu; Chen, Xin; Moy, Sheryl S.; Saddoris, Kara A.; Nikolova, Viktoriya; Farrell, Martilias S.; Wang, Sheng; Mangano, Thomas J.; Deshpande, Deepak A.; Jiang, Alice; Penn, Raymond B.; Jin, Jian; Koller, Beverly H.; Kenakin, Terry; Shoichet, Brian K.; Roth, Bryan L.

    2016-01-01

    At least 120 non-olfactory G protein-coupled receptors in the human genome are ”orphans” for which endogenous ligands are unknown, and many have no selective ligands, hindering elucidation of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Yeast-based screens against GPR68 identified the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. Over 3000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators many of which were confirmed in functional assays. One potent GPR68 modulator—ogerin– suppressed recall in fear conditioning in wild-type, but not in GPR68 knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

  13. Gender-typical olfactory regulation of sexual behavior in goldfish

    PubMed Central

    Kawaguchi, Yutaro; Nagaoka, Akira; Kitami, Asana; Mitsuhashi, Tomomi; Hayakawa, Youichi; Kobayashi, Makito

    2014-01-01

    It is known that olfaction is essential for the occurrence of sexual behavior in male goldfish. Sex pheromones from ovulatory females elicit male sexual behavior, chasing, and sperm releasing act. In female goldfish, ovarian prostaglandin F2α (PGF) elicits female sexual behavior, egg releasing act. It has been considered that olfaction does not affect sexual behavior in female goldfish. In the present study, we re-examined the involvement of olfaction in sexual behavior of female goldfish. Olfaction was blocked in male and female goldfish by two methods: nasal occlusion (NO) which blocks the reception of olfactants, and olfactory tract section (OTX) which blocks transmission of olfactory information from the olfactory bulb to the telencephalon. Sexual behavior of goldfish was induced by administration of PGF to females, an established method for inducing goldfish sexual behavior in both sexes. Sexual behavior in males was suppressed by NO and OTX as previously reported because of lack of pheromone stimulation. In females, NO suppressed sexual behavior but OTX did not affect the occurrence of sexual behavior. Females treated with both NO and OTX performed sexual behavior normally. These results indicate that olfaction is essential in female goldfish to perform sexual behavior as in males but in a different manner. The lack of olfaction in males causes lack of pheromonal stimulation, resulting in no behavior elicited. Whereas the results of female experiments suggest that lack of olfaction in females causes strong inhibition of sexual behavior mediated by the olfactory pathway. Olfactory tract section is considered to block the pathway and remove this inhibition, resulting in the resumption of the behavior. By subtract sectioning of the olfactory tract, it was found that this inhibition was mediated by the medial olfactory tracts, not the lateral olfactory tracts. Thus, it is concluded that goldfish has gender-typical olfactory regulation for sexual behavior. PMID

  14. Enhanced olfactory sensitivity in autism spectrum conditions.

    PubMed

    Ashwin, Chris; Chapman, Emma; Howells, Jessica; Rhydderch, Danielle; Walker, Ian; Baron-Cohen, Simon

    2014-01-01

    People with autism spectrum conditions (ASC) report heightened olfaction. Previous sensory experiments in people with ASC have reported hypersensitivity across visual, tactile, and auditory domains, but not olfaction. The aims of the present study were to investigate olfactory sensitivity in ASC, and to test the association of sensitivity to autistic traits. We recruited 17 adult males diagnosed with ASC and 17 typical adult male controls and tested their olfactory sensitivity using the Alcohol Sniff Test (AST), a standardised clinical evaluation of olfactory detection. The AST involves varying the distance between subject and stimulus until an odour is barely detected. Participants with ASC also completed the Autism Spectrum Quotient (AQ) as a measure of autism traits. The ASC group detected the odour at a mean distance of 24.1 cm (SD =11.5) from the nose, compared to the control group, who detected it at a significantly shorter mean distance of 14.4 cm (SD =5.9). Detection distance was independent of age and IQ for both groups, but showed a significant positive correlation with autistic traits in the ASC group (r =0.522). This is the first experimental demonstration, as far as the authors are aware, of superior olfactory perception in ASC and showing that greater olfactory sensitivity is correlated with a higher number of autistic traits. This is consistent with results from previous findings showing hypersensitivity in other sensory domains and may help explain anecdotal and questionnaire accounts of heightened olfactory sensitivity in ASC. Results are discussed in terms of possible underlying neurophysiology.

  15. Long term serious olfactory loss in colds and/or flu.

    PubMed

    de Haro-Licer, Josep; Roura-Moreno, Jordi; Vizitiu, Anabella; González-Fernández, Adela; González-Ares, Josep Antón

    2013-01-01

    In the general population, we can find 2-3% of lifelong olfactory disorders (from hyposmia to anosmia). Two of the most frequent aetiologies are the common cold and flu. The aim of this study was to show the degree of long-term olfactory dysfunction caused by a cold or flu. This study was based on 240 patients, with olfactory loss caused only by flu or a cold. We excluded all patients with concomitant illness (66 patients), the rest of patients (n=174) consisted of 51 men (29.3%) and 123 women (70.7%). They all underwent olfactometry study (i and v cranial nerve) and a nasal sinus computed tomography scan, as well as magnetic resonance imaging of the brain. Results were compared with a control group (n=120). Very significant differences in levels of olfactory impairment for the olfactory nerve (P<.00001) and trigeminal nerve (P<.0001) were confirmed. People that suffer olfactory dysfunction for more than 6 months, from flu or a cold, present serious impairment of olfactory abilities. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. Olfactory circuits and behaviors of nematodes.

    PubMed

    Rengarajan, Sophie; Hallem, Elissa A

    2016-12-01

    Over one billion people worldwide are infected with parasitic nematodes. Many parasitic nematodes actively search for hosts to infect using volatile chemical cues, so understanding the olfactory signals that drive host seeking may elucidate new pathways for preventing infections. The free-living nematode Caenorhabditis elegans is a powerful model for parasitic nematodes: because sensory neuroanatomy is conserved across nematode species, an understanding of the microcircuits that mediate olfaction in C. elegans may inform studies of olfaction in parasitic nematodes. Here we review circuit mechanisms that allow C. elegans to respond to odorants, gases, and pheromones. We also highlight work on the olfactory behaviors of parasitic nematodes that lays the groundwork for future studies of their olfactory microcircuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Time frequency analysis of olfactory induced EEG-power change.

    PubMed

    Schriever, Valentin Alexander; Han, Pengfei; Weise, Stefanie; Hösel, Franziska; Pellegrino, Robert; Hummel, Thomas

    2017-01-01

    The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function. A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects. Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III. Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

  18. Determinants of human olfactory performance: a cross-cultural study.

    PubMed

    Sorokowska, Agnieszka; Sorokowski, Piotr; Frackowiak, Tomasz

    2015-02-15

    Olfaction allows us to detect subtle changes in our environment, but sensitivity of the sense of smell varies among individuals. Although a significant number of research papers discuss the relationship between olfactory abilities and environmental factors, most studies have been conducted on Western populations or in developed Asian societies. The potential environmental and cultural determinants of olfactory acuity warrant further exploration. In the current study, we compared previously published data on olfaction in an industrialized, modern society (i.e., Europeans) and an indigenous society living in unpolluted, natural environmental conditions (i.e., Tsimane'), with novel data on the olfactory acuity of inhabitants of the Cook Islands. Like the European population (and contrary to the Tsimane'), the Cook Islands people form a modern society, and like the Tsimane' population (and contrary to the Europeans), they live in an unpolluted region. Thus, these comparisons enabled us to independently assess the importance of both air pollution and changes in lifestyle for olfactory abilities in modern societies. Our results indicate that people from the Cook Islands had significantly higher olfactory acuity (i.e., lower thresholds of odor detection) than did Europeans and Tsimane' people. Interestingly, the olfactory sensitivity of Europeans was significantly lower than the olfactory sensitivity of the remaining two groups. Our data suggest that air pollution is an important factor in the deterioration of the sense of smell. However, it is also possible that factors such as agricultural and/or cooking practices, alcohol consumption, and access to medical service may also influence olfactory acuity. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Unraveling Cajal's view of the olfactory system

    PubMed Central

    Figueres-Oñate, María; Gutiérrez, Yolanda; López-Mascaraque, Laura

    2014-01-01

    The olfactory system has a highly regular organization of interconnected synaptic circuits from the periphery. It is therefore an excellent model for understanding general principles about how the brain processes information. Cajal revealed the basic cell types and their interconnections at the end of the XIX century. Since his original descriptions, the observation and analysis of the olfactory system and its components represents a major topic in neuroscience studies, providing important insights into the neural mechanisms. In this review, we will highlight the importance of Cajal contributions and his legacy to the actual knowledge of the olfactory system. PMID:25071462

  20. Associative Processes in Early Olfactory Preference Acquisition

    PubMed Central

    Sullivan, Regina M.; Wilson, Donald A.; Leon, Michael

    2007-01-01

    Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of 14C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses. PMID:17572798