Science.gov

Sample records for adult olfactory epithelium

  1. Sensory Cell Proliferation within the Olfactory Epithelium of Developing Adult Manduca sexta (Lepidoptera)

    PubMed Central

    Franco, Marie-dominique; Bohbot, Jonathan; Fernandez, Kenny; Hanna, Jayd; Poppy, James; Vogt, Richard

    2007-01-01

    Background Insects detect a multitude of odors using a broad array of phenotypically distinct olfactory organs referred to as olfactory sensilla. Each sensillum contains one to several sensory neurons and at least three support cells; these cells arise from mitotic activities from one or a small group of defined precursor cells. Sensilla phenotypes are defined by distinct morphologies, and specificities to specific odors; these are the consequence of developmental programs expressed by associated neurons and support cells, and by selection and expression of subpopulations of olfactory genes encoding such proteins as odor receptors, odorant binding proteins, and odor degrading enzymes. Methodology/Principal Findings We are investigating development of the olfactory epithelium of adult M. sexta, identifying events which might establish sensilla phenotypes. In the present study, antennal tissue was examined during the first three days of an 18 day development, a period when sensory mitotic activity was previously reported to occur. Each antenna develops as a cylinder with an outward facing sensory epithelium divided into approximately 80 repeat units or annuli. Mitotic proliferation of sensory cells initiated about 20–24 hrs after pupation (a.p.), in pre-existing zones of high density cells lining the proximal and distal borders of each annulus. These high density zones were observed as early as two hr. a.p., and expanded with mitotic activity to fill the mid-annular regions by about 72 hrs a.p. Mitotic activity initiated at a low rate, increasing dramatically after 40–48 hrs a.p.; this activity was enhanced by ecdysteroids, but did not occur in animals entering pupal diapause (which is also ecdysteroid sensitive). Conclusions/Significance Sensory proliferation initiates in narrow zones along the proximal and distal borders of each annulus; these zones rapidly expand to fill the mid-annular regions. These zones exist prior to any mitotic activity as regions of

  2. Olfactory Epithelium Grafts in the Cerebral Cortex: An Immunohistochemical Analysis

    PubMed Central

    Holbrook, Eric H.; DiNardo, Laurence J.; Costanzo, Richard M.

    2009-01-01

    Objective To develop an alternative model for studying the regenerative capacity of olfactory neurons. Study Design An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. Methods Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. Results Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. Conclusions Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration. PMID:11801979

  3. Notch2 is required for maintaining sustentacular cell function in the adult mouse main olfactory epithelium

    PubMed Central

    Rodriguez, Steve; Sickles, Heather M.; DeLeonardis, Chris; Alcaraz, Ana; Gridley, Thomas; Lin, David M.

    2008-01-01

    Notch receptors are expressed in neurons and glia in the adult nervous system, but why this expression persists is not well-understood. Here we examine the role of the Notch pathway in the postnatal mouse main olfactory system, and show evidence consistent with a model where Notch2 is required for maintaining sustentacular cell function. In the absence of Notch2, the laminar nature of these glial-like cells is disrupted. Hes1, Hey1, and Six1, which are downstream effectors of the Notch pathway, are down-regulated, and cytochrome P450 and Glutathione S-transferase (GST) expression by sustentacular cells is reduced. Functional levels of GST activity are also reduced. These disruptions are associated with increased olfactory sensory neuron degeneration. Surprisingly, expression of Notch3 is also down-regulated. This suggests the existence of a feedback loop where expression of Notch3 is initially independent of Notch2, but requires Notch2 for maintained expression. While the Notch pathway has previously been shown to be important for promoting gliogenesis during development, this is the first demonstration that the persistent expression of Notch receptors is required for maintaining glial function in adult. PMID:18155189

  4. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    SciTech Connect

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  5. 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

  6. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  7. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  8. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings. PMID:7647371

  9. Nested expression domains for odorant receptors in zebrafish olfactory epithelium.

    PubMed

    Weth, F; Nadler, W; Korsching, S

    1996-11-12

    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. PMID:8917589

  10. The nasal cavity of the sheep and its olfactory sensory epithelium.

    PubMed

    Barrios, Arthur William; Sanchez Quinteiro, Pablo; Salazar, Ignacio

    2014-12-01

    Macro and microdissection methods, conventional histology and immunohistochemical procedures were used to investigate the nasal cavity and turbinate complex in fetal and adult sheep, with special attention to the ethmoturbinates, the vestibular mucosa, and the septal mucosa posterior to the vomeronasal organ. The ectoturbinates, which are variable in number and size, emerge and develop later than the endoturbinates. The olfactory sensory epithelium is composed of basal cells, neurons, and sustentacular cells organized in strata, but numerous different types are distinguishable on the basis of their thickness and other properties; all variants are present on the more developed turbinates, endoturbinates II and III. Mature neurons and olfactory nerve bundles express olfactory marker protein. We found no structure with the characteristics that in mouse define the septal organ or the ganglion of Grüneberg. Our results thus suggest that in sheep olfactory sensory neurons are exclusively concentrated in the main olfactory epithelium and (to a lesser extent) in the vomeronasal organ. PMID:25213000

  11. Adult Olfactory Bulb Neurogenesis.

    PubMed

    Lledo, Pierre-Marie; Valley, Matt

    2016-01-01

    Most organisms use their olfactory system to detect and analyze chemical cues from the external world to guide essential behaviors. From worms to vertebrates, chemicals are detected by odorant receptors expressed by olfactory sensory neurons, which in vertebrates send an axon to the primary processing center called the olfactory bulb (OB). Within the OB, sensory neurons form excitatory synapses with projection neurons and with inhibitory interneurons. Thus, because of complex synaptic interactions, the output of a given projection neuron is determined not only by the sensory input, but also by the activity of local inhibitory interneurons that are regenerated throughout life in the process of adult neurogenesis. Herein, we discuss how it is optimized and why. PMID:27235474

  12. Properties of odour-binding glycoproteins from rat olfactory epithelium.

    PubMed

    Fesenko, E E; Novoselov, V I; Bystrova, M F

    1988-01-22

    The specific membrane glycoproteins with high affinity for camphor and decanal were isolated from rat olfactory epithelium. Antibodies to these glycoproteins inhibited both the electroolfactogram and the binding of odorants. The enzyme immunoassay has shown these glycoproteins to be present in the olfactory epithelium of rat, mouse, guinea-pig and hamster but not in that of frog and carp. The molecular mass of the odour-binding glycoproteins from rat olfactory epithelium solubilized by Triton X-100 was approx. 140 kDa. They consisted of two subunits (88 and 55 kDa). The 88 kDa subunit was capable of binding odorants. The data obtained suggest that the glycoproteins isolated have some properties that make them plausible candidates for olfactory receptor molecules. PMID:3337807

  13. Responses of the rat olfactory epithelium to retronasal air flow.

    PubMed

    Scott, John W; Acevedo, Humberto P; Sherrill, Lisa; Phan, Maggie

    2007-03-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very nonpolar, hydrophobic odorants were used. Although the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the nonpolar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recordings from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally versus retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  14. Responses of the Rat Olfactory Epithelium to Retronasal Air Flow

    PubMed Central

    Scott, John W.; Acevedo, Humberto P.; Sherrill, Lisa; Phan, Maggie

    2008-01-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very non-polar, hydrophobic odorants were used. While the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the non-polar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recording from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally vs. retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  15. Transcriptional regulatory network during development in the olfactory epithelium

    PubMed Central

    Im, SeungYeong; Moon, Cheil

    2015-01-01

    Regeneration, a process of reconstitution of the entire tissue, occurs throughout life in the olfactory epithelium (OE). Regeneration of OE consists of several stages: proliferation of progenitors, cell fate determination between neuronal and non-neuronal lineages, their differentiation and maturation. How the differentiated cell types that comprise the OE are regenerated, is one of the central questions in olfactory developmental neurobiology. The past decade has witnessed considerable progress regarding the regulation of transcription factors (TFs) involved in the remarkable regenerative potential of OE. Here, we review current state of knowledge of the transcriptional regulatory networks that are powerful modulators of the acquisition and maintenance of developmental stages during regeneration in the OE. Advance in our understanding of regeneration will not only shed light on the basic principles of adult plasticity of cell identity, but may also lead to new approaches for using stem cells and reprogramming after injury or degenerative neurological diseases. [BMB Reports 2015; 48(11): 599-608] PMID:26303973

  16. Expression of homeobox genes in the mouse olfactory epithelium.

    PubMed

    Parrilla, Marta; Chang, Isabelle; Degl'Innocenti, Andrea; Omura, Masayo

    2016-10-01

    Homeobox genes constitute a large family of genes widely studied because of their role in the establishment of the body pattern. However, they are also involved in many other events during development and adulthood. The main olfactory epithelium (MOE) is an excellent model to study neurogenesis in the adult nervous system. Analyses of homeobox genes during development show that some of these genes are involved in the formation and establishment of cell diversity in the MOE. Moreover, the mechanisms of expression of odorant receptors (ORs) constitute one of the biggest enigmas in the field. Analyses of OR promoters revealed the presence of homeodomain binding sites in their sequences. Here we characterize the expression patterns of a set of 49 homeobox genes in the MOE with in situ hybridization. We found that seven of them (Dlx3, Dlx5, Dlx6, Msx1, Meis1, Isl1, and Pitx1) are zonally expressed. The homeobox gene Emx1 is expressed in three guanylate cyclase(+) populations, two located in the MOE and the third one in an olfactory subsystem known as Grüneberg ganglion located at the entrance of the nasal cavity. The homeobox gene Tshz1 is expressed in a unique patchy pattern across the MOE. Our findings provide new insights to guide functional studies that aim to understand the complexity of transcription factor expression and gene regulation in the MOE. J. Comp. Neurol. 524:2713-2739, 2016. © 2016 Wiley Periodicals, Inc. PMID:27243442

  17. Functional Evidence of Multidrug Resistance Transporters (MDR) in Rodent Olfactory Epithelium

    PubMed Central

    Molinas, Adrien; Sicard, Gilles; Jakob, Ingrid

    2012-01-01

    Background P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. Principal Findings Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of species-specific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG). In both animal species, MRPs inhibitors induced a marked reduction of the EOG magnitude, while Pgp inhibitors had only a minor or no measurable effect. Conclusions The findings suggest that both Pgp and MRP transporters are functional in the olfactory mucosa and in olfactory receptor neurons. Pgp and MRPs may be cellular constituents of olfactory receptor neurons and represent potential

  18. Plasticity of Glomeruli and Olfactory-Mediated Behavior in Zebrafish Following Detergent Lesioning of the Olfactory Epithelium

    PubMed Central

    White, Evan J.; Kounelis, Savannah K.; Byrd-Jacobs, Christine A.

    2014-01-01

    The zebrafish olfactory system is a valuable model for examining neural regeneration after damage due to the remarkable plasticity of this sensory system and of fish species. We applied detergent to the olfactory organ and examined the effects on both morphology and function of the olfactory system in adult zebrafish. Olfactory organs were treated once with Triton X-100 unilaterally to study glomerular innervation patterns or bilaterally to study odor detection. Fish were allowed to recover for 4–10 days and were compared to untreated control fish. Axonal projections were analyzed using whole mount immunocytochemistry with anti-keyhole limpet hemocyanin, a marker of olfactory axons in teleosts. Chemical lesioning of the olfactory organ with a single dose of Triton X-100 had profound effects on glomerular distribution in the olfactory bulb at 4 days after treatment, with the most significant effects in the medial region of the bulb. Glomeruli had returned by 7 days post-treatment. Analysis of the ability of the fish to detect cocktails of amino acids or bile salts consisted of counting the number of turns the fish made before and after odorant delivery. Control fish turned more after exposure to both odorants. Fish tested 4 and 7 days after chemical lesioning made more turns in response to amino acids but did not respond to bile salts. At 10 days post-lesion, these fish had regained the ability to detect bile salts. Thus, the changes seen in bulbar innervation patterns correlated to odorant-mediated behavior. We show that the adult zebrafish brain has the capacity to recover rapidly from detergent damage of the olfactory epithelium, with both glomerular distribution and odorant-mediated behavior returning in 10 days. PMID:25450960

  19. Plasticity of glomeruli and olfactory-mediated behavior in zebrafish following detergent lesioning of the olfactory epithelium.

    PubMed

    White, E J; Kounelis, S K; Byrd-Jacobs, C A

    2015-01-22

    The zebrafish olfactory system is a valuable model for examining neural regeneration after damage due to the remarkable plasticity of this sensory system and of fish species. We applied detergent to the olfactory organ and examined the effects on both morphology and function of the olfactory system in adult zebrafish. Olfactory organs were treated once with Triton X-100 unilaterally to study glomerular innervation patterns or bilaterally to study odor detection. Fish were allowed to recover for 4-10 days and were compared to untreated control fish. Axonal projections were analyzed using whole mount immunocytochemistry with anti-keyhole limpet hemocyanin, a marker of olfactory axons in teleosts. Chemical lesioning of the olfactory organ with a single dose of Triton X-100 had profound effects on glomerular distribution in the olfactory bulb at 4 days after treatment, with the most significant effects in the medial region of the bulb. Glomeruli had returned by 7 days post-treatment. Analysis of the ability of the fish to detect cocktails of amino acids or bile salts consisted of counting the number of turns the fish made before and after odorant delivery. Control fish turned more after exposure to both odorants. Fish tested 4 and 7 days after chemical lesioning made more turns in response to amino acids but did not respond to bile salts. At 10 days post-lesion, these fish had regained the ability to detect bile salts. Thus, the changes seen in bulbar innervation patterns correlated to odorant-mediated behavior. We show that the adult zebrafish brain has the capacity to recover rapidly from detergent damage of the olfactory epithelium, with both glomerular distribution and odorant-mediated behavior returning in 10 days. PMID:25450960

  20. Site-specific population dynamics and variable olfactory marker protein expression in the postnatal canine olfactory epithelium

    PubMed Central

    Bock, Patricia; Rohn, Karl; Beineke, Andreas; Baumgärtner, Wolfgang; Wewetzer, Konstantin

    2009-01-01

    The main olfactory epithelium is a pseudostratified columnar epithelium that displays neurogenesis over the course of a lifetime. New olfactory neurons arise basally and are transferred to the middle third of the epithelium during maturation. It is generally believed that this pattern is present throughout the olfactory area. In the present study, we show that the postnatal canine olfactory epithelium is composed of two distinct types of epithelium, designated A and B, which not only differ in olfactory neuron morphology, marker expression and basal cell proliferation but also display a patchy distribution and preferential localization within the nasal cavity. Type A epithelium, abundant in the caudal part of the olfactory area, contains well-differentiated olfactory neurons positive for olfactory marker protein but low numbers of immature neurons and proliferating basal cells, as visualized by TrkB/Human Natural Killer-1 (HNK-1) glyco-epitope and Ki-67 immunostaining, respectively. In contrast, type B epithelium is mainly found in the rostral part and contains smaller and elongated neurons that display increased levels of TrkB/Human Natural Killer-1 (HNK-1) glyco-epitope immunoreactivity and a higher number of Ki-67-positive basal cells but lower and variable levels of olfactory marker protein. The vomeronasal organ displays a uniform distribution of molecular markers and proliferating basal cells. The observation that olfactory marker protein in type A and B epithelium is preferentially localized to the nucleus and cytoplasm, respectively, implies correlation between subcellular localization and olfactory neuron maturation and may indicate distinct functional roles of olfactory marker protein. Whether the site-specific population dynamics in the postnatal canine olfactory epithelium revealed in the present study are modulated by physiological parameters, such as airflow, has to be clarified in future studies. PMID:19788548

  1. Cannabinoid receptor signaling induces proliferation but not neurogenesis in the mouse olfactory epithelium.

    PubMed

    Hutch, Chelsea R; Hegg, Colleen C

    2016-01-01

    The olfactory epithelium actively generates neurons through adulthood, and this neurogenesis is tightly regulated by multiple factors that are not fully defined. Here, we examined the role of cannabinoids in the regulation of neurogenesis in the mouse olfactory epithelium. In vivo proliferation and cell lineage studies were performed in mice (C57BL/6 and cannabinoid type 1 and 2 receptor deficient strains) treated with cannabinoids directly (WIN 55,212-2 or 2-arachidonylglycerol ether) or indirectly via inhibition of cannabinoid hydrolytic enzymes. Cannabinoids increased proliferation in neonatal and adult mice, and had no effect on proliferation in cannabinoid type 1 and 2 receptor deficient adult mice. Pretreatment with the cannabinoid type1 receptor antagonist AM251 decreased cannabinoid-induced proliferation in adult mice. Despite a cannabinoid-induced increase in proliferation, there was no change in newly generated neurons or non-neuronal cells 16 d post-treatment. However, cannabinoid administration increased apoptotic cell death at 72 hours post-treatment and by 16 d the level of apoptosis dropped to control levels. Thus, cannabinoids induce proliferation, but do not induce neurogenesis nor non-neuronal cell generation. Cannabinoid receptor signaling may regulate the balance of progenitor cell survival and proliferation in adult mouse olfactory epithelium. PMID:27606334

  2. Odorant-evoked potassium changes in the frog olfactory epithelium.

    PubMed

    Khayari, A; Math, F; Trotier, D

    1991-01-18

    Electroolfactogram (EOG) and extracellular potassium activity (aK) measurements were carried out in frog olfactory epithelia in vivo. Odorant-evoked changes in aK were characterized on the basis of depth profile analysis. Following an olfactory stimulation with butanol vapours, an increase in aK was measured in the mucus and the proximal part of the epithelium; this response started after the beginning of the EOG and was proportional to the amplitude of the latter. In the deeper part of the epithelium, the aK response had complex waveforms showing an initial K decrease which was suppressed by local application of ouabain, suggesting the existence of a pumping mechanism at this level. The results are discussed in terms of extracellular accumulation of K ions following neuroreceptor activation with respect to EOG generation theories. PMID:2015495

  3. Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium

    PubMed Central

    Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R.

    2016-01-01

    Olfactory sensory neurons in the main olfactory epithelium (MOE) are responsible for detecting odorants and EOG recording is a reliable approach to analyze the peripheral olfactory function. However, recently we revealed that rodent MOE can also detect the air pressure caused by airflow. The sensation of airflow pressure and odorants may function in synergy to facilitate odorant perception during sniffing. We have reported that the pressure-sensitive response in the MOE can also be assayed by EOG recording. Here we describe procedures for pressure-sensitive as well as odorant-stimulated EOG measurement in the mouse MOE. The major difference between the pressure-sensitive EOG response and the odorant-stimulated response was whether to use pure air puff or use an odorized air puff.

  4. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium

    PubMed Central

    Nickell, William T; Kleene, Nancy K; Kleene, Steven J

    2007-01-01

    When olfactory receptor neurons respond to odours, a depolarizing Cl− efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl− against an electrochemical gradient. In isolated olfactory receptor neurons, the Na+–K+–2Cl− cotransporter NKCC1 is essential for Cl− accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl− efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl− accumulation. To identify the remaining transport proteins, we first screened by RT-PCR for 21 Cl− transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl− transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl− transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl−/HCO3− exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild-type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na+–Cl− cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl−/HCO3− exchangers, reduced the EOG in epithelia from both wild-type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl− component of the response. These results support the involvement of both NKCC1 and one or more DIDS-sensitive transporters in Cl− accumulation in olfactory receptor neurons. PMID:17656441

  5. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.

    PubMed

    Nickell, William T; Kleene, Nancy K; Kleene, Steven J

    2007-09-15

    When olfactory receptor neurons respond to odours, a depolarizing Cl(-) efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl(-) against an electrochemical gradient. In isolated olfactory receptor neurons, the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 is essential for Cl(-) accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl(-) efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl(-) accumulation. To identify the remaining transport proteins, we first screened by RT-PCR for 21 Cl(-) transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl(-) transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl(-) transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl(-)/HCO(3)(-) exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild-type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na(+)-Cl(-) cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl(-)/HCO(3)(-) exchangers, reduced the EOG in epithelia from both wild-type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl(-) component of the response. These results support the involvement of both NKCC1 and one or more DIDS-sensitive transporters in Cl(-) accumulation in olfactory receptor neurons. PMID:17656441

  6. 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. PMID:27003941

  7. Expression of Nogo receptor 1 in the regeneration process of the mouse olfactory epithelium.

    PubMed

    Chen, He-Xin; Zeng, Xian-Ping; Sun, Yue-Qi; Fu, Qing-Ling

    2016-07-01

    Nogo receptor 1 (NgR1) is the most important Nogo-A receptor. By its interaction with myelin-associated inhibitory proteins, NgR1 inhibits the regeneration of axons and is extensively expressed in the central nervous system. However, the expression of NgR1 in regenerable neurons, such as olfactory neurons, and its expression in the regeneration progress of olfactory neurons have not been reported. In this study, we demonstrated that NgR1 was expressed in the cell bodies of certain mature olfactory receptor neurons (ORNs) but was not expressed in immature ORNs in the olfactory epithelium (OE) of normal adult mice. On day 21 after OE injury, NgR1 was expressed not only in the cell bodies of mature ORNs but also in the cell bodies of glial fibrillary acidic protein (GFAP)-positive cells in the top and submucosal layers of the OE. On day 48 after model establishment, NgR1 expression decreased in the cell bodies of the GFAP-positive cells. On day 56 after model establishment, no NgR1 expression was found in the cell bodies of the GFAP-positive cells, and NgR1 was again expressed only in the mature ORNs. Our results demonstrated that NgR1 expression is upregulated in the OE after injury, which suggests that NgR1 might be involved in the regeneration of the OE. PMID:27138950

  8. Spatially organized response zones in rat olfactory epithelium.

    PubMed

    Scott, J W; Shannon, D E; Charpentier, J; Davis, L M; Kaplan, C

    1997-04-01

    Electroolfactogram recordings were made with a four-electrode assembly from the olfactory epithelium overlying the endoturbinate bones facing the nasal septum. In this study we tested whether odors of different chemical structures produce maximal responses along longitudinally oriented regions following the olfactory receptor gene expression zones described in the literature. The distribution of responses along the dorsal-to-ventral direction of this epithelium (i.e., across the expression zones) was tested in two types of experiments. In one, four electrodes were fixed along the dorsal-to-ventral axis of one turbinate bone. In the other, four electrodes were placed in corresponding positions on four turbinate bones and moved together up toward the top of the bone. These experiments compared the odorants limonene and alpha-terpinene, which are simple hydrocarbons, with carvone and menthone, which differ from the hydrocarbons by the presence of ketone groups. All responses were standardized to an amyl acetate or ethyl butyrate standard. The responses to limonene and alpha-terpinene were often larger for the ventral electrodes. The responses to carvone and menthone were largest for the dorsal electrodes. Intermediate electrodes gave responses that were intermediate in amplitude for these odors. The possibility that direction of air flow caused the observed response distributions was directly tested in experiments with odor nozzles placed in two positions. The relatively larger dorsal responses to carvone and relatively larger ventral responses to limonene were present despite odor nozzle position. We conclude that the responses to this set of odors vary systematically in a fashion parallel to the four gene expression zones. The odorant property that governs this response distribution may be related to the presence of oxygen-containing functional groups. Certain odors evoked larger responses at the intermediate electrode sites than at other sites. Cineole was the best

  9. Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium

    PubMed Central

    Joiner, Ariell M.; Green, Warren W.; McIntyre, Jeremy C.; Allen, Benjamin L.; Schwob, James E.

    2015-01-01

    The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specific Ift88 knock-out mouse line (K5rtTA;tetOCre;Ift88fl/fl) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. SIGNIFICANCE STATEMENT We show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory

  10. An autoradiographic study of the mouse olfactory epithelium: evidence for long-lived receptors.

    PubMed

    Hinds, J W; Hinds, P L; McNelly, N A

    1984-10-01

    In order to try to determine whether differentiated olfactory receptors turn over (die and are replaced by newly differentiated cells) during adult life, mice were injected with a single dose of 3H-thymidine at either 2 or 4 months of age and allowed to survive for up to 12 months; they were caged in a laminar flow unit to prevent rhinitis. Counts of labeled receptor cells detected autoradiographically after injection at 2 months of age revealed that, following an initial decrease from 1 to 3 months of survival, numbers of labeled cells remained approximately constant, at least up to 12 months of survival. Cells still labeled at 12 months of survival were confirmed as receptor cells by electron microscopic examination of reembedded sections. The hypothesis is suggested that in the absence of disease-related destruction of the olfactory epithelium, most or all receptor cell turnover represents newly formed cells that fail to establish synapses with the olfactory bulb; fully differentiated receptor cells may be quite long-lived. PMID:6542328

  11. PACAP protects against TNFα-induced cell death in olfactory epithelium and olfactory placodal cell lines

    PubMed Central

    Kanekar, Shami; Gandham, Mahendra; Lucero, Mary T

    2010-01-01

    In mouse olfactory epithelium (OE), pituitary adenylate cyclase activating peptide (PACAP) protects against axotomy-induced apoptosis. We used mouse OE to determine whether PACAP protects neurons during exposure to the inflammatory cytokine TNFα. Live slices of neonatal mouse OE were treated with 40 ng/ml TNFα ± 40 nM PACAP for 6 hours and dying cells were live-labeled with 0.5% propidium iodide. TNFα significantly increased the percentage of dying cells while co-incubation with PACAP prevented cell death. PACAP also prevented TNFα-mediated cell death in the olfactory placodal (OP) cell lines, OP6 and OP27. Although OP cell lines express all three PACAP receptors (PAC1, VPAC1,VPAC2), PACAP’s protection of these cells from TNFα was mimicked by the specific PAC1 receptor agonist maxadilan and abolished by the PAC1 antagonist PACAP6–38. Treatment of OP cell lines with blockers or activators of the PLC and AC/MAPKK pathways revealed that PACAP-mediated protection from TNFα involved both pathways. PACAP may therefore function through PAC1 receptors to protect neurons from cell death during inflammatory cytokine release in vivo as would occur upon viral infection or allergic rhinitis-associated injury. PMID:20654718

  12. An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction

    PubMed Central

    Hutch, Chelsea; Hillard, Cecilia J.; Jia, Cuihong; Hegg, Colleen C.

    2015-01-01

    Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium has not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1 and CB2 receptor deficient (CB1−/−/CB2−/−) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1−/−/CB2−/− mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1−/−/CB2−/− mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted. PMID:26037800

  13. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    PubMed Central

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  14. Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium.

    PubMed

    Wittmann, Walter; Schimmang, Thomas; Gunhaga, Lena

    2014-06-01

    N-myc belongs to the myc proto-oncogene family, which is involved in numerous cellular processes such as proliferation, growth, apoptosis, and differentiation. Conditional deletion of N-myc in the mouse nervous system disrupted brain development, indicating that N-myc plays an essential role during neural development. How the development of the olfactory epithelium and neurogenesis within are affected by the loss of N-myc has, however, not been determined. To address these issues, we examined an N-myc(Foxg1Cre) conditional mouse line, in which N-myc is depleted in the olfactory epithelium. First changes in N-myc mutants were detected at E11.5, with reduced proliferation and neurogenesis in a slightly smaller olfactory epithelium. The phenotype was more pronounced at E13.5, with a complete lack of Hes5-positive progenitor cells, decreased proliferation, and neurogenesis. In addition, stereological analyses revealed reduced cell size of post-mitotic neurons in the olfactory epithelium, which contributed to a smaller olfactory pit. Furthermore, we observed diminished proliferation and neurogenesis also in the vomeronasal organ, which likewise was reduced in size. In addition, the generation of gonadotropin-releasing hormone neurons was severely reduced in N-myc mutants. Thus, diminished neurogenesis and proliferation in combination with smaller neurons might explain the morphological defects in the N-myc depleted olfactory structures. Moreover, our results suggest an important role for N-myc in regulating ongoing neurogenesis, in part by maintaining the Hes5-positive progenitor pool. In summary, our results provide evidence that N-myc deficiency in the olfactory epithelium progressively diminishes proliferation and neurogenesis with negative consequences at structural and cellular levels. PMID:24376126

  15. Glutathione S-transferases in rat olfactory epithelium: purification, molecular properties and odorant biotransformation.

    PubMed Central

    Ben-Arie, N; Khen, M; Lancet, D

    1993-01-01

    The olfactory epithelium is exposed to a variety of xenobiotic chemicals, including odorants and airborne toxic compounds. Recently, two novel, highly abundant, olfactory-specific biotransformation enzymes have been identified: cytochrome P-450olf1 and olfactory UDP-glucuronosyltransferase (UGT(olf)). The latter is a phase II biotransformation enzyme which catalyses the glucuronidation of alcohols, thiols, amines and carboxylic acids. Such covalent modification, which markedly affects lipid solubility and agonist potency, may be particularly important in the rapid termination of odorant signals. We report here the identification and characterization of a second olfactory phase II biotransformation enzyme, a glutathione S-transferase (GST). The olfactory epithelial cytosol shows the highest GST activity among the extrahepatic tissues examined. Significantly, olfactory epithelium had an activity 4-7 times higher than in other airway tissues, suggesting a role for this enzyme in chemoreception. The olfactory GST has been affinity-purified to homogeneity, and shown by h.p.l.c. and N-terminal amino acid sequencing to constitute mainly the Yb1 and Yb2 subunits, different from most other tissues that have mixtures of more enzyme classes. The identity of the olfactory enzymes was confirmed by PCR cloning and restriction enzyme analysis. Most importantly, the olfactory GSTs were found to catalyse glutathione conjugation of several odorant classes, including many unsaturated aldehydes and ketones, as well as epoxides. Together with UGT(olf), olfactory GST provides the necessary broad coverage of covalent modification capacity, which may be crucial for the acuity of the olfactory process. Images Figure 1 Figure 4 Figure 5 PMID:8503873

  16. Analysis of the goldfish Carassius auratus olfactory epithelium transcriptome reveals the presence of numerous non-olfactory GPCR and putative receptors for progestin pheromones

    PubMed Central

    Kolmakov, Nikolay N; Kube, Michael; Reinhardt, Richard; Canario, Adelino VM

    2008-01-01

    Background The goldfish (Carassius auratus) uses steroids and prostaglandins as pheromone cues at different stages of the reproductive cycle to facilitate spawning synchronization. Steroid progestin pheromone binding has been detected in goldfish olfactory membranes but the receptors responsible for this specific binding remain unknown. In order to shed some light on the olfactory epithelium transcriptome and search for possible receptor candidates a large set of EST from this tissue were analysed and compared to and combined with a similar zebrafish (Danio rerio) resource. Results We generated 4,797 high quality sequences from a normalized cDNA library of the goldfish olfactory epithelium, which were clustered in 3,879 unique sequences, grouped in 668 contigs and 3,211 singletons. BLASTX searches produced 3,243 significant (E-value < e-10) hits and Gene Ontology (GO) analysis annotated a further 1,223 of these genes (37.7%). Comparative analysis with zebrafish olfactory epithelium ESTs revealed 1,088 identical unigenes. The transcriptome size of both species was estimated at about 16,400 unigenes, based on the proportion of genes identified involved in Glucose Metabolic Process. Of 124 G-protein coupled receptors identified in the olfactory epithelium of both species, 56 were olfactory receptors. Beta and gamma membrane progestin receptors were also isolated by subcloning of RT-PCR products from both species and an olfactory epithelium specific splice form identified. Conclusion The high similarity between the goldfish and zebrafish olfactory systems allowed the creation of a 'cyprinid' olfactory epithelium library estimated to represent circa 70% of the transcriptome. These results are an important resource for the identification of components of signalling pathways involved in olfaction as well as putative targets for pharmacological and histochemical studies. The possible function of the receptors identified in the olfactory system is described. Moreover, the

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

    PubMed

    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

  18. 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

  19. CD36 is expressed in a defined subpopulation of neurons in the olfactory epithelium.

    PubMed

    Xavier, André Machado; Ludwig, Raissa Guimarães; Nagai, Maíra Harume; de Almeida, Tiago Jonas; Watanabe, Hebe Mizuno; Hirata, Marcio Yukio; Rosenstock, Tatiana Rosado; Papes, Fabio; Malnic, Bettina; Glezer, Isaias

    2016-01-01

    The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction. PMID:27145700

  20. CD36 is expressed in a defined subpopulation of neurons in the olfactory epithelium

    PubMed Central

    Xavier, André Machado; Ludwig, Raissa Guimarães; Nagai, Maíra Harume; de Almeida, Tiago Jonas; Watanabe, Hebe Mizuno; Hirata, Marcio Yukio; Rosenstock, Tatiana Rosado; Papes, Fabio; Malnic, Bettina; Glezer, Isaias

    2016-01-01

    The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction. PMID:27145700

  1. Response of the hammerhead shark olfactory epithelium to amino acid stimuli.

    PubMed

    Tricas, Timothy C; Kajiura, Stephen M; Summers, Adam P

    2009-10-01

    Sharks and rays are highly sensitive to chemical stimuli in their natural environment but several hypotheses predict that hammerhead sharks, with their expanded head and enlarged olfactory epithelium, have particularly acute olfactory systems. We used the electro-olfactogram (EOG) technique to compare the relative response of the scalloped hammerhead shark (Sphyrna lewini) olfactory epithelium to 20 proteinogenic amino acids and determine the sensitivity for 6 amino acids. At micromolar concentrations, cysteine evoked the greatest EOG response which was approximately twice as large as that of alanine. The weakest response was obtained for proline followed by aspartic acid and isoleucine. The olfactory epithelium showed adaptation to sequential stimulation, and recovery was related to the inter-stimulus time period. Estimated EOG response thresholds were in the sub-nanomolar range for both alanine (9.2 x 10(-11) M) and cysteine (8.4 x 10(-10) M) and in the micromolar range for proline and serine. These thresholds from 10(-10) to 10(-6) M for the scalloped hammerhead shark are comparable or lower than those reported for other teleost and elasmobranch species. Future work should focus on binary and more complex compounds to test for competition and cross-adaptation for different classes of peripheral receptors, and their responses to molecules found in biologically relevant stimuli. PMID:19711087

  2. Sox2 and Pax6 Play Counteracting Roles in Regulating Neurogenesis within the Murine Olfactory Epithelium

    PubMed Central

    Packard, Adam I.; Lin, Brian; Schwob, James E.

    2016-01-01

    In the adult olfactory epithelium, the transcription factors Pax6 and Sox2 are co-expressed in sustentacular cells, horizontal basal cells (HBCs), and less-differentiated globose basal cells (GBCs)–both multipotent and transit amplifying categories—but are absent from immediate neuronal precursor GBCs and olfactory sensory neurons (OSNs). We used retroviral-vector transduction to over-express Pax6 and Sox2 individually and together during post-lesion recovery to determine how they regulate neuronal differentiation. Both Pax6 and Sox2, separately and together, can suppress the production of OSNs, as fewer clones contain neurons than with empty vector (EV), although this effect is not absolute. In this regard, Pax6 has the strongest effect when acting alone. In clones where neurons form, Pax6 reduces neuron numbers by comparison with EV, while Sox2 expands their numbers. Co-transduction with Pax6 and Sox2 produces an intermediate result. The increased production of OSNs driven by Sox2 is due to the expansion of neuronal progenitors, since proliferation and the numbers of Ascl1, Neurog1, and NeuroD1-expressing GBCs are increased. Conversely, Pax6 seems to accelerate neuronal differentiation, since Ascl1 labeling is reduced, while Neurog1- and NeuroD1-labeled GBCs are enriched. As a complement to the over-expression experiments, elimination of Sox2 in spared cells of floxed Sox2 mice, by retroviral Cre or by K5-driven CreERT2, reduces the production of OSNs and non-neuronal cells during OE regeneration. These data suggest that Pax6 and Sox2 have counteracting roles in regulating neurogenesis, in which Pax6 accelerates neuronal production, while Sox2 retards it and expands the pool of neuronal progenitors. PMID:27171428

  3. Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium.

    PubMed

    Monti-Bloch, L; Grosser, B I

    1991-10-01

    The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones. PMID:1892788

  4. Expressions of the multidrug resistance-related proteins in the rat olfactory epithelium: a possible role in the phase III xenobiotic metabolizing function.

    PubMed

    Kudo, Hideaki; Doi, Yoshiaki; Fujimoto, Sunao

    2010-01-01

    The xenobiotic metabolizing system is considered to play important roles in the olfaction by the chemical homeostasis. Several phase I and phase II xenobiotic metabolizing enzymes are expressed in the olfactory epithelium in vertebrates. Multidrug resistance-related proteins (MRPs) are the phase III xenobiotic metabolizing pumps that eliminate some conjugated ligands from cells. However, the MRP-expressions in the olfactory epithelium have not been confirmed in the mammals. We investigated gene and protein expressions of MRP type 1 (MRP1) and type 2 (MRP2) isoforms in the adult rat olfactory epithelium in order to clarify the existence of phase III xenobiotic metabolizing pumps in the olfactory organs. Expressions of MRP1 mRNA were detected in the nasal cavity by reverse transcriptase polymerase chain reaction (RT-PCR). The nucleoside sequence of the RT-PCR products were completely identical to that found in other organs of rat. On the contrary, the analysis did not detect expressions of MRP2 mRNA in the nasal cavity. By in situ hybridization using a digoxigenin-labeled MRP1 cRNA probe, signals for MRP1 mRNA were observed preferentially in the perinuclear regions of supporting cells. However, the respiratory epithelial cells did not show the signals for MRP1 mRNA. By immunohistochemistry using a specific antibody to MRP1, MRP1-immunoreactivities were seen mainly on the supporting cells. These findings suggest that MRP1 is involved in olfaction as a part of the "olfactory signal termination" by the chemical homeostasis in the "perireceptor events" of the olfactory epithelium. PMID:19879335

  5. Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity

    SciTech Connect

    Dahl, A.R.; Hadley, W.M.; Hahn, F.F.; Benson, J.M.; McClellan, R.O.

    1982-04-02

    The respiratory tract epithelium of dogs, from the nose to the lungs, was examined for cytochrome P-450 and associated biotransformation activities. In the ethmoturbinates, where olfactory epithelium is located, the amount of cytochrome P-450 was comparable to that in the liver, when measured on the basis of activity per milligram of microsomal protein. The rest of the nasal region also contained large quantities of cytochrome P-450. The presence of these enzymes in the nose may be important in chemical-induced tumorigenesis. The nasal carcinogen hexamethylphosphoramide was shown to be metabolized by nasal microsomal enzymes to another nasal carcinogen, formaldehyde.

  6. In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs.

    PubMed

    Zippel, H P

    2000-09-29

    Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (10(-6) M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in 'incorrect' position (i) and (ii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii). PMID:11079402

  7. Microwave effect on camphor binding to rat olfactory epithelium

    SciTech Connect

    Philippova, T.M.; Novoselov, V.I.; Bystrova, M.F.; Alekseev, S.I.

    1988-01-01

    Microwave radiation decreased specific camphor binding to a membrane fraction of rat epithelium but not to a Triton X-100 extract of this fraction. Inhibition of the ligand binding did not depend on the modulation frequency of the microwave field in the region 1-100 Hz and was not a linear function of specific absorption rate (SAR). The decreased ligand binding was due to a shedding or release of the specific camphor-binding protein from the membrane into solution. It is highly probable that several other membrane proteins may be shed into solution during microwave exposure.

  8. Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice

    PubMed Central

    Wang, Zhenshan; Zhou, Yanfen; Luo, Yingtao; Zhang, Jing; Zhai, Yunpeng; Yang, Dong; Zhang, Zhe; Li, Yongchao; Storm, Daniel R.; Ma, Runlin Z.

    2015-01-01

    Adenylyl Cyclase 3 (AC3) plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE). In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/−) and wild-type (AC3+/+) mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels between AC3−/− and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up regulated, and 1988 were down regulated, including 425 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE. PMID:26633363

  9. Adult Neurogenesis and the Olfactory System

    PubMed Central

    Whitman, Mary C.; Greer, Charles A.

    2009-01-01

    Though initially described in the early 1960s, it is only within the past decade that the concept of continuing adult neurogenesis has gained widespread acceptance. Neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) into the olfactory bulb, where they differentiate into interneurons. Neuroblasts from the subgranular zone (SGZ) of the hippocampal formation show relatively little migratory behavior, and differentiate into dentate gyrus granule cells. In sharp contrast to embryonic and perinatal development, these newly differentiated neurons must integrate into a fully functional circuit, without disrupting ongoing performance. Here, after a brief historical overview and introduction to olfactory circuitry, we review recent advances in the biology of neural stem cells, mechanisms of migration in the RMS and olfactory bulb, differentiation and survival of new neurons, and finally mechanisms of synaptic integration. Our primary focus is on the olfactory system, but we also contrast the events occurring there with those in the hippocampal formation. Although both SVZ and SGZ neurogenesis are involved in some types of learning, their full functional significance remains unclear. Since both systems offer models of integration of new neuroblasts, there is immense interest in using neural stem cells to replace neurons lost in injury or disease. Though many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. We discuss here some of the central features of these advances, as well as speculate on future research directions. PMID:19615423

  10. Expression and Localization of the Cell Adhesion Molecule SgIGSF during Regeneration of the Olfactory Epithelium in Mice

    PubMed Central

    Tsukioka, Fusae; Wakayama, Tomohiko; Tsukatani, Toshiaki; Miwa, Takaki; Furukawa, Mitsuru; Iseki, Shoichi

    2007-01-01

    Spermatogenic immunoglobulin superfamily (SgIGSF) is a cell adhesion molecule originally discovered in mouse testis. SgIGSF is expressed not only in spermatogenic cells but also in lung and liver epithelial cells and in neurons and glia of the central and peripheral nervous systems. In the present study, we examined the expression and localization of SgIGSF in mouse olfactory epithelium before and after transection of the olfactory nerves, by RT-PCR, Western blotting and immunohistochemistry. In normal olfactory mucosa, SgIGSF showed 100 kDa in molecular weight, which was identical with that in the lung but different from that in the brain. SgIGSF was expressed on the membrane of all olfactory, sustentacular and basal cells, but more abundantly in the apical portions of the olfactory epithelium where the dendrites of olfactory cells are in contact with sustentacular cells. After olfactory nerve transection, mature olfactory cells disappeared in 4 days but were regenerated around 7–15 days by proliferation and differentiation of basal cells into mature olfactory cells through the step of immature olfactory cells. During this period, both the mRNA and protein for SgIGSF showed a transient increase, with peak levels at 7 days and 11 days, respectively, after the transection. Immunohistochemistry showed that the enriched immunoreactivity for SgIGSF at 7–11 days was localized primarily to the membrane of immature olfactory cells. These results suggested that, during regeneration of the olfactory epithelium, the adhesion molecule SgIGSF plays physiological roles in differentiation, migration, and maturation of immature olfactory cells. PMID:17576432

  11. 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

  12. Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish.

    PubMed

    Hentig, James T; Byrd-Jacobs, Christine A

    2016-01-01

    Zinc sulfate is a known olfactory toxicant, although its specific effects on the olfactory epithelium of zebrafish are unknown. Olfactory organs of adult zebrafish were exposed to zinc sulfate and, after 2, 3, 5, 7, 10 or 14 days, fish were processed for histological, immunohistochemical, ultrastructural, and behavioral analyses. Severe morphological disruption of the olfactory organ was observed two days following zinc sulfate exposure, including fusion of lamellae, epithelial inflammation, and significant loss of anti-calretinin labeling. Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated structures, but microvilli were still present. Behavioral analysis showed significant loss of the ability to perceive bile salts and some fish also had no response to amino acids. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin labeling returned to control-like conditions, although the ability to perceive bile salts remained lost until day 14. Thus, exposure to zinc sulfate results in rapid degeneration of the olfactory organ, followed by restoration of morphology and function within two weeks. Zinc sulfate appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory sensory neurons, suggesting differential effects on sensory neuron subtypes. PMID:27589738

  13. Identification and molecular regulation of neural stem cells in the olfactory epithelium

    SciTech Connect

    Beites, Crestina L.; Kawauchi, Shimako; Crocker, Candice E.; Calof, Anne L. . E-mail: alcalof@uci.edu

    2005-06-10

    The sensory neurons that subserve olfaction, olfactory receptor neurons (ORNs), are regenerated throughout life, making the neuroepithelium in which they reside [the olfactory epithelium (OE)] an excellent model for studying how intrinsic and extrinsic factors regulate stem cell dynamics and neurogenesis during development and regeneration. Numerous studies indicate that transcription factors and signaling molecules together regulate generation of ORNs from stem and progenitor cells during development, and work on regenerative neurogenesis indicates that these same factors may operate at postnatal ages as well. This review describes our current knowledge of the identity of the OE neural stem cell; the different cell types that are thought to be the progeny (directly or indirectly) of this stem cell; and the factors that influence cell differentiation in the OE neuronal lineage. We review data suggesting that (1) the ORN lineage contains three distinct proliferating cell types-a stem cell and two populations of transit amplifying cells; (2) in established OE, these three cell types are present within the basal cell compartment of the epithelium; and (3) the stem cell that gives rise ultimately to ORNs may also generate two glial cell types of the primary olfactory pathway: sustentacular cells (SUS), which lie within OE proper; and olfactory ensheathing cells (OEC), which envelope the olfactory nerve. In addition, we describe factors that are both made by and found within the microenvironment of OE stem and progenitor cells, and which exert crucial growth regulatory effects on these cells. Thus, as with other regenerating tissues, the basis of regeneration in the OE appears be a population of stem cells, which resides within a microenvironment (niche) consisting of factors crucial for maintenance of its capacity for proliferation and differentiation.

  14. Expression of the NMDA receptor subunit GluN3A (NR3A) in the olfactory system and its regulatory role on olfaction in the adult mouse.

    PubMed

    Lee, Jin Hwan; Wei, Ling; Deveau, Todd C; Gu, Xiaohuan; Yu, Shan Ping

    2016-07-01

    Glutamate is an excitatory neurotransmitter in the olfactory system and its N-methyl-D-aspartate-(NMDA) receptor subunits [GluN1 (NR1), GluN2A (NR2A), and GluN2B (NR2B)] are expressed at synapses in the olfactory bulb and olfactory epithelium. Thus, glutamatergic neurons and NMDA receptors play key roles in olfaction. GluN3A (NR3A) is a unique inhibitory subunit in the NMDA receptor complex; however, the expression and functional role of GluN3A in the olfactory bulb and epithelium remain unclear. The present study examined the expression patterns of GluN3A in the olfactory bulb and epithelium and explored its functional role in the olfactory system. Immunohistochemical and Western blot analyses revealed that GluN3A is abundantly expressed in different cellular layers of the olfactory bulb and epithelium of the adult wild type (WT) mice. In littermate GluN3A knockout (GluN3A(-/-); KO) mice, the expression of olfactory marker protein normally found in mature olfactory sensory neurons was significantly reduced in the olfactory bulb and epithelium. A butyl alcohol stimulus increased immediate-early gene c-Fos expression in the olfactory system of WT mice, while this response was absent in GluN3A KO mice. The level of phosphorylated Ca(2+)/calmodulin-dependent kinase II was significantly lower in GluN3A KO mice compared to WT mice. In buried food finding test, GluN3A mice took significantly longer time to find food compared to WT mice. Consistently, impaired odor distinguishing ability was seen in GluN3A KO mice. These findings suggest that GluN3A, expressed in the adult olfactory system, plays a significant regulatory role in olfactory development and functional activity. PMID:26334321

  15. Development of the Olfactory Epithelium and Nasal Glands in TMEM16A-/- and TMEM16A+/+ Mice

    PubMed Central

    Maurya, Devendra Kumar; Henriques, Tiago; Marini, Monica; Pedemonte, Nicoletta; Galietta, Luis J. V.; Rock, Jason R.; Harfe, Brian D.; Menini, Anna

    2015-01-01

    TMEM16A/ANO1 is a calcium-activated chloride channel expressed in several types of epithelia and involved in various physiological processes, including proliferation and development. During mouse embryonic development, the expression of TMEM16A in the olfactory epithelium is dynamic. TMEM16A is expressed at the apical surface of the entire olfactory epithelium at embryonic day E12.5 while from E16.5 its expression is restricted to a region near the transition zone with the respiratory epithelium. To investigate whether TMEM16A plays a role in the development of the mouse olfactory epithelium, we obtained the first immunohistochemistry study comparing the morphological properties of the olfactory epithelium and nasal glands in TMEM16A-/- and TMEM16A+/+ littermate mice. A comparison between the expression of the olfactory marker protein and adenylyl cyclase III shows that genetic ablation of TMEM16A did not seem to affect the maturation of olfactory sensory neurons and their ciliary layer. As TMEM16A is expressed at the apical part of supporting cells and in their microvilli, we used ezrin and cytokeratin 8 as markers of microvilli and cell body of supporting cells, respectively, and found that morphology and development of supporting cells were similar in TMEM16A-/- and TMEM16A+/+ littermate mice. The average number of supporting cells, olfactory sensory neurons, horizontal and globose basal cells were not significantly different in the two types of mice. Moreover, we also observed that the morphology of Bowman’s glands, nasal septal glands and lateral nasal glands did not change in the absence of TMEM16A. Our results indicate that the development of mouse olfactory epithelium and nasal glands does not seem to be affected by the genetic ablation of TMEM16A. PMID:26067252

  16. Neuronal chloride accumulation in olfactory epithelium of mice lacking NKCC1

    PubMed Central

    Nickell, William T.; Kleene, Nancy K.; Gesteland, Robert C.; Kleene, Steven J.

    2005-01-01

    When stimulated with odorants, olfactory receptor neurons (ORNs) produce a depolarizing receptor current. In isolated ORNs, much of this current is due to an efflux of Cl−. This implies that the neurons have one or more mechanisms for accumulating cytoplasmic Cl− at rest. Whether odors activate an efflux of Cl− in intact olfactory epithelium, where the ionic environment is poorly characterized, has not been previously determined. In mouse olfactory epithelium, we find that >80% of the summated electrical response to odors is blocked by niflumic acid or flufenamic acid, each of which inhibits Ca2+-activated Cl− channels in ORNs. This indicates that ORNs accumulate Cl− in situ. Recent evidence has shown that NKCC1, a Na+-K+-2Cl− cotransporter, contributes to Cl− accumulation in mammalian ORNs. However, we find that the epithelial response to odors is only reduced by 39% in mice carrying a null mutation in Nkcc1. As in the wild type, most of the response is blocked by niflumic acid or flufenamic acid, indicating that the underlying current is carried by Cl−. We conclude that ORNs effectively accumulate Cl− in situ even in the absence of NKCC1. The Cl−-transport mechanism underlying this accumulation has not yet been identified. PMID:16319203

  17. Defence mechanisms of olfactory neuro-epithelium: mucosa regeneration, metabolising enzymes and transporters.

    PubMed

    Watelet, J B; Strolin-Benedetti, M; Whomsley, R

    2009-01-01

    The olfactory neuro-epithelium is highly sensitive to chemicals and its direct microbiological environment. It also plays a role as an interface between the airways and the nervous system, and so it has developed several defence instruments for rapid regeneration or for the detoxification of the immediate environment. This review illustrates three of these defence mechanisms: regeneration of the epithelium, local production of metabolising enzymes and xenobiotic transporters. Toxicants can inflict damage by a direct toxic response. Alternatively, they may require metabolic activation to produce the proximate toxicant. In addition to detoxifying inhaled and systemically derived xenobiotics, the local olfactory metabolism may fulfil multiple functions such as the modification of inhaled odorant, the modulation of endogenous signalling molecules and the protection of other tissues such as the CNS and lungs from inhaled toxicants. Finally, the permeability of nasal and olfactory mucosa is an important efficacy parameter for some anti-allergic drugs delivered by intranasal administration or inhalation. Efflux or update transporters expressed in these tissues may therefore significantly influence the pharmacokinetics of drugs administered topically. PMID:20084803

  18. Secretion and electrogenesis of the supporting cell in the olfactory epithelium

    PubMed Central

    Okano, Masaomi; Takagi, Sadayuki F.

    1974-01-01

    1. Electrophysiological study disclosed that chloroform and some other odours generate long-lasting positive potentials in the olfactory epithelium of the bullfrog, while electron microscopical study showed that they elicit vigorous protrusion of the distal cytoplasmic portion of the supporting cell containing the secretory granules. 2. The secretory process of the supporting cell is as follows: The first detectable indication is the protrusion of the apical portion of the supporting cell (Pls. 3 and 4); the protruded part detaches from its maternal supporting cell (Pl. 7 B), floats as a droplet in the mucus (Pl. 5), and finally the secretory granules inside the droplet disintegrate into the mucus (Pls. 6 and 7 A). 3. The secretion was not elicited by the odours which elicit the negative potentials. 4. In Cl--free Ringer solution, neither the positive potential nor the protrusion and secretion occurred. 5. When 1-2 mM-Ba2+ in Ringer solution was dripped on the epithelium, both the positive potential and the protrusion and secretion resulted. Subsequent application of chloroform vapour only advanced further disintegration of the secretory granules, but it elicited neither a new protrusion of the granules nor the positive potential. 6. In the olfactory epithelium in which the olfactory cells had degenerated but the supporting cells survived, both the positive potential and the protrusion and secretion occurred, but the negative potential did not. 7. It is concluded that Cl- entry which mainly generates the longlasting positive potential triggers the secretion of the supporting cell. ImagesABPlate 5Plate 6ABPlate 8ABABABAB PMID:4549073

  19. Phospholipase C and diacylglycerol mediate olfactory responses to amino acids in the main olfactory epithelium of an amphibian.

    PubMed

    Sansone, Alfredo; Hassenklöver, Thomas; Syed, Adnan S; Korsching, Sigrun I; Manzini, Ivan

    2014-01-01

    The semi-aquatic lifestyle of amphibians represents a unique opportunity to study the molecular driving forces involved in the transition of aquatic to terrestrial olfaction in vertebrates. Most amphibians have anatomically segregated main and vomeronasal olfactory systems, but at the cellular and molecular level the segregation differs from that found in mammals. We have recently shown that amino acid responses in the main olfactory epithelium (MOE) of larval Xenopus laevis segregate into a lateral and a medial processing stream, and that the former is part of a vomeronasal type 2 receptor expression zone in the MOE. We hypothesized that the lateral amino acid responses might be mediated via a vomeronasal-like transduction machinery. Here we report that amino acid-responsive receptor neurons in the lateral MOE employ a phospholipase C (PLC) and diacylglycerol-mediated transduction cascade that is independent of Ca(2+) store depletion. Furthermore, we found that putative transient receptor potential (TRP) channel blockers inhibit most amino acid-evoked responses in the lateral MOE, suggesting that ion channels belonging to the TRP family may be involved in the signaling pathway. Our data show, for the first time, a widespread PLC- and diacylglycerol-dependent transduction cascade in the MOE of a vertebrate already possessing a vomeronasal organ. PMID:24489954

  20. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

    PubMed Central

    Hohenbrink, Philipp; Dempewolf, Silke; Zimmermann, Elke; Mundy, Nicholas I.; Radespiel, Ute

    2014-01-01

    The vomeronasal organ (VNO) is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR) genes comprise two families of chemosensory genes (V1R and V2R) that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE) of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the gray mouse lemur (Microcebus murinus), the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83–97%) of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29 to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information. PMID:25309343

  1. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs.

    PubMed

    Hohenbrink, Philipp; Dempewolf, Silke; Zimmermann, Elke; Mundy, Nicholas I; Radespiel, Ute

    2014-01-01

    The vomeronasal organ (VNO) is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR) genes comprise two families of chemosensory genes (V1R and V2R) that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE) of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the gray mouse lemur (Microcebus murinus), the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83-97%) of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29 to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information. PMID:25309343

  2. Lesion of the main olfactory epithelium facilitates maternal behavior in virgin rabbits.

    PubMed

    Chirino, Rosario; Beyer, Carlos; González-Mariscal, Gabriela

    2007-06-18

    Maternal behavior is induced in virgin female rabbits (normally unresponsive to foster pups) by removing the accessory olfactory bulbs. To determine if the main olfactory system (MOS) plays a similar inhibitory role in the present work we investigated the effect of lesioning the olfactory epithelium with a ZnSO(4) spray on the facilitation of maternal behavior in New Zealand white virgin rabbits. Four days after the chemical lesion 40% of females showed behaviors indistinguishable from those of normal mothers, i.e.: rapid entrance into the nest box containing the pups, adoption of a crouching posture over them, acceptance of suckling, and exit from the nest box after ca. 3min. The proportion of females showing these behaviors rose to 70% by day 14 post-lesion. Ovariectomized rabbits sprayed with ZnSO(4) or animals sprayed with NaCl did not behave maternally. ZnSO(4) also provoked a transient reduction in olfactory perception: before the lesion animals from all groups directed significantly more sniffs to a flask containing male urine than to one containing water. This difference was abolished in ZnSO(4)-sprayed females (intact and ovariectomized) for 3-6 days post-lesion and was re-established by 7-9 days. NaCl did not provoke such transitory hyposmia. ZnSO(4) lesions did not provoke malaise in the animals, as determined by food intake and the frequency of scent-marking and ambulation. Results suggest that olfactory cues from the pups are aversive to virgin rabbits and that a transitory reduction in their perception (accompanied by the action of ovarian secretions) is enough to facilitate maternal responsiveness. PMID:17412432

  3. Effects of gustatory stimulants upon the olfactory epithelium of the bullfrog and the carp.

    PubMed

    Takagi, S F; Iino, M; Yarita, H

    1978-01-01

    Effects of various gustatory stimulants upon the olfactory spithelia were examined in the olfactory bulb of the bullfrog and the carp. 1. The olfactory epithelia of the two animals responded to the salty, bitter- and acid-tasting substances, but not to the sweet ones. 2. The olfactory epithelium of the bullfrog responded immediately to sodium solutions of high concentrations (the "initial response"), but the response to those of low concentrations showed long latency (the "delayed response"). In the carp, the "initial response" was found, while the "delayed response" was not in most cases. A "negative" delayed response was found only infrequently. 3. Responses only to high alkali or acid solutions were found in the two animals. 4. When 0.05 M NaCl was added to HCl solutions, an enhancing effect was found in the bullfrog, while a reducing effect occurred in the carp. On the contrary, when 0.05 M NaCl was added to NaOH solutions, an enhancing effect occurred in the carp, while no consistent result was founding the bullfrog. 5. Many amino acids were effective stimuli in the bullfrog, but only betaine and 1-aspartic acid were found effective in the carp. 6. Changes in temperatures beyond 35 degrees C or under 10 degrees C elicited responses. Mechanical stimuli were effective in the carp, but not in the bullfrog. 7. The "water response" was found in the bullfrog, but not in the carp. 8. Sensitivities of the olfactory epithelia of the two animals were compared and discussed. PMID:308564

  4. Functional Analysis Of The Guanylyl Cyclase Type D Signaling System In The Olfactory Epithelium

    PubMed Central

    Cockerham, Renee E.; Leinders-Zufall, Trese; Munger, Steven D.; Zufall, Frank

    2013-01-01

    The mammalian olfactory system recognizes a wide range of chemical stimuli. The majority of cells in the main olfactory epithelium (MOE) use a cAMP-mediated signaling system to transduce odor signals. However, a subset of MOE neurons instead expresses components of a cGMP signaling cascade, including the receptor guanylyl cyclase GC-D and the cyclic nucleotide-gated channel subunit CNGA3. We used a combination of molecular biological, physiological and imaging approaches to characterize this neuronal population. Neurons expressing GC-D show excitatory responses to the natriuretic peptide hormones uroguanylin and guanylin, as well as to stimuli present in urine, that are dependent on both GC-D and CNGA3. Though all GC-D-expressing neurons are highly sensitive to these stimuli, individual cells are differentially tuned to either one or both of the peptides. Together, these findings suggest that neurons expressing GC-D are part of a specialized olfactory subsystem that is responsive to semiochemicals. PMID:19686132

  5. Electroolfactogram responses from organotypic cultures of the olfactory epithelium from postnatal mice.

    PubMed

    Pinato, Giulietta; Rievaj, Juraj; Pifferi, Simone; Dibattista, Michele; Masten, Lara; Menini, Anna

    2008-04-01

    Organotypic cultures of the mouse olfactory epithelium connected to the olfactory bulb were obtained with the roller tube technique from postnatal mice aged between 13 and 66 days. To test the functionality of the cultures, we measured electroolfactograms (EOGs) at different days in vitro (DIV), up to 7 DIV, and we compared them with EOGs from identical acute preparations (0 DIV). Average amplitudes of EOG responses to 2 mixtures of various odorants at concentrations of 1 mM or 100 microM decreased in cultures between 2 and 5 DIV compared with 0 DIV. The percentage of responsive cultures was 57%. We also used the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) to trigger the olfactory transduction cascade bypassing odorant receptor activation. Average amplitudes of EOG responses to 500 microM IBMX were not significantly different in cultures up to 6 DIV or 0 DIV, and the average percentage of responsive cultures between 2 and 5 DIV was 72%. The dose-response curve to IBMX measured in cultures up to 7 DIV was similar to that at 0 DIV. Moreover, the percentage of EOG response to IBMX blocked by niflumic acid, a blocker of Ca-activated Cl channels, was not significantly different in cultured or acute preparations. PMID:18303030

  6. Relation of chemical structure to spatial distribution of sensory responses in rat olfactory epithelium.

    PubMed

    Scott, J W; Davis, L M; Shannon, D; Kaplan, C

    1996-05-01

    1. Electroolfactogram (EOG) recordings were made in three configurations from the rat olfactory epithelium. Each configuration compared recordings in the dorsomedial recess of the epithelium with recordings in ventral or lateral parts of the epithelium. Most comparisons were made with simultaneous recordings. The exception was a series in which the dorsal recess and lateral space between the base of two turbinate bones were directly exposed for odor application and recording. The spatial distributions of maximal responses were largely independent of recording configuration. 2. Simultaneous recordings compared dorsomedial and lateral sites in the epithelium during stimulation with a series of 50 odorants. The odorants that evoked larger responses in the lateral sites were usually compounds that lacked oxygen containing functional groups (such as the carbonyl group). This was true for straight chain and cyclic alkanes, for terpine compounds, and for aromatic compounds. The major exception was cineole, a bicyclic compound. All compounds containing ketone groups evoked larger dorsomedial responses. The responses of aldehydes and esters depended upon whether they were attached to aliphatic or aromatic chains. 3. In the three types of preparation, the sites responding best to ketones were in the same expression zone of the epithelium according to published maps for the rat and mouse. The sites responding best to odors without functional groups were in the far lateral or ventral region and corresponded to one of the two most lateral and ventral expression zones. This fact suggests that the receptors in these regions have a preference for particular chemical properties. This level of analysis cannot determine whether all receptors in each zone have a stronger response to certain properties of these odorants or whether each zone contains different proportions of receptors with these properties. PMID:8734602

  7. 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

  8. Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

    PubMed Central

    Leinders-Zufall, Trese; Cockerham, Renee E.; Michalakis, Stylianos; Biel, Martin; Garbers, David L.; Reed, Randall R.; Zufall, Frank; Munger, Steven D.

    2007-01-01

    The mammalian main olfactory epithelium (MOE) recognizes and transduces olfactory cues through a G protein-coupled, cAMP-dependent signaling cascade. Additional chemosensory transduction mechanisms have been suggested but remain controversial. We show that a subset of MOE neurons expressing the orphan receptor guanylyl cyclase GC-D and the cyclic nucleotide-gated channel subunit CNGA3 employ an excitatory cGMP-dependent transduction mechanism for chemodetection. By combining gene targeting of Gucy2d, which encodes GC-D, with patch clamp recording and confocal Ca2+ imaging from single dendritic knobs in situ, we find that GC-D cells recognize the peptide hormones uroguanylin and guanylin as well as natural urine stimuli. These molecules stimulate an excitatory, cGMP-dependent signaling cascade that increases intracellular Ca2+ and action potential firing. Responses are eliminated in both Gucy2d- and Cnga3-null mice, demonstrating the essential role of GC-D and CNGA3 in the transduction of these molecules. The sensitive and selective detection of two important natriuretic peptides by the GC-D neurons suggests the possibility that these cells contribute to the maintenance of salt and water homeostasis or the detection of cues related to hunger, satiety, or thirst. PMID:17724338

  9. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium

    PubMed Central

    Katsunuma, Sayaka; Honda, Hisao; Shinoda, Tomoyasu; Ishimoto, Yukitaka; Miyata, Takaki; Kiyonari, Hiroshi; Abe, Takaya; Nibu, Ken-ichi; Takai, Yoshimi

    2016-01-01

    In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via α-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism. PMID:26929452

  10. Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

    PubMed Central

    Schnittke, Nikolai; Herrick, Daniel B.; Lin, Brian; Peterson, Jesse; Coleman, Julie H.; Packard, Adam I.; Jang, Woochan; Schwob, James E.

    2015-01-01

    Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs. PMID:26305958

  11. Response of olfactory axons to loss of synaptic targets in the adult mouse

    PubMed Central

    Ardiles, Yona; de la Puente, Rafael; Toledo, Rafael; Isgor, Ceylan; Guthrie, Kathleen

    2007-01-01

    Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-D-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by three weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by eight weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets. PMID:17674970

  12. Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium.

    PubMed

    Miyake, Mio; Ito, Yuki; Sawada, Masato; Sakai, Kiyoshi; Suzuki, Himiko; Sakamoto, Tatsuo; Sawamoto, Kazunobu; Kamijima, Michihiro

    2016-08-01

    The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H. PMID:27055686

  13. Changes in the adult vertebrate auditory sensory epithelium after trauma.

    PubMed

    Oesterle, Elizabeth C

    2013-03-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  14. A comparative study of axon-surrounding cells in the two nasal nerve tracts from mouse olfactory epithelium and vomeronasal organ.

    PubMed

    Nakajima, Mitsunari; Tsuruta, Momoko; Mori, Hisamichi; Nishikawa, Chisa; Okuyama, Satoshi; Furukawa, Yoshiko

    2013-03-29

    The olfactory and vomeronasal systems are the two nasal chemical detectors in mammals. While glial cells in the olfactory nerve tracts have been well-investigated, little is known about cells in the vomeronasal nerve tracts. In the present study, we compared the expression patterns of marker proteins in the cells comprising the two nasal nerve tracts in mice. Neural crest-derived cells surrounded the olfactory nerve axons in the lamina propria of the olfactory epithelium. These cells expressed glial fibrillary acidic protein (GFAP) and p75 glycoprotein, which are markers of olfactory ensheathing cells. Neural crest-derived cells also surrounded the vomeronasal nerve axons in the lamina propria of the vomeronasal epithelium. These nerve axon-surrounding cells, however, did not express GFAP or p75. Rather, the vomeronasal nerve axons expressed GFAP and p75. These results suggest that axon-surrounding cells functionally differ between the olfactory and vomeronasal nerve tracts. PMID:23410787

  15. Reversible Deafferentation of the Adult Zebrafish Olfactory Bulb Affects Glomerular Distribution and Olfactory-Mediated Behavior

    PubMed Central

    Paskin, Taylor R.; Byrd-Jacobs, Christine A.

    2012-01-01

    The olfactory system is a useful model for studying central nervous system recovery from damage due to its neuroplasticity. We recently developed a novel method of deafferentation by repeated exposure of Triton X-100 to the olfactory organ of adult zebrafish. This long-term, reversible method of deafferentation allows both degeneration and regeneration to be observed in the olfactory bulb. The aim of the present study is to examine olfactory bulb innervation, glomerular patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment and the potential for recovery following cessation of treatment. Olfactory bulbs of control, chronic-treated, and recovery animals were examined for the presence or absence of glomeruli that have been identified in the zebrafish glomerular map. Following chronic treatment, the number of glomeruli was dramatically reduced; however, partial innervation remained in the lateral region of the bulb. When animals were given time to recover, complete glomerular distribution returned. A behavioral assay was developed to determine if innervation remaining correlated with behavior of the fish. Chronic-treated fish did not respond to odorants involved with social behavior but continued to react to odorants that mediate feeding behavior. Following recovery, responses to odorants involved with social behavior returned. The morphological and behavioral effects of chronic Triton X-100 treatment in the olfactory system suggest there may be differential susceptibility or resistance to external damage in a subset of sensory neurons. The results of this study demonstrate the remarkable regenerative ability of the olfactory system following extensive and long-term injury. PMID:22963994

  16. Reversible deafferentation of the adult zebrafish olfactory bulb affects glomerular distribution and olfactory-mediated behavior.

    PubMed

    Paskin, Taylor R; Byrd-Jacobs, Christine A

    2012-12-01

    The olfactory system is a useful model for studying central nervous system recovery from damage due to its neuroplasticity. We recently developed a novel method of deafferentation by repeated exposure of Triton X-100 to the olfactory organ of adult zebrafish. This long-term, reversible method of deafferentation allows both degeneration and regeneration to be observed in the olfactory bulb. The aim of the present study is to examine olfactory bulb innervation, glomerular patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment and the potential for recovery following cessation of treatment. Olfactory bulbs of control, chronic-treated, and recovery animals were examined for the presence or absence of glomeruli that have been identified in the zebrafish glomerular map. Following chronic treatment, the number of glomeruli was dramatically reduced; however, partial innervation remained in the lateral region of the bulb. When animals were given time to recover, complete glomerular distribution returned. A behavioral assay was developed to determine if innervation remaining correlated with behavior of the fish. Chronic-treated fish did not respond to odorants involved with social behavior but continued to react to odorants that mediate feeding behavior. Following recovery, responses to odorants involved with social behavior returned. The morphological and behavioral effects of chronic Triton X-100 treatment in the olfactory system suggest there may be differential susceptibility or resistance to external damage in a subset of sensory neurons. The results of this study demonstrate the remarkable regenerative ability of the olfactory system following extensive and long-term injury. PMID:22963994

  17. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  18. Amphibian larvae and zinc sulphate: a suitable model to study the role of brain-derived neurotrophic factor (BDNF) in the neuronal turnover of the olfactory epithelium.

    PubMed

    Yovanovich, Carola A M; Jungblut, Lucas D; Heer, Tamara; Pozzi, Andrea G; Paz, Dante A

    2009-04-01

    The vertebrate olfactory system has fascinated neurobiologists over the last six decades because of its ability to replace its neurons and synaptic connections continuously throughout adult life, under both physiological and pathological conditions. Among the factors that are proposed to be involved in this regenerative potential, brain-derived neurotrophic factor (BDNF) is a candidate for having an important role in the neuronal turnover in the olfactory epithelium (OE) because of its well-documented neurogenic and trophic effects throughout the nervous system. The aim of the present study was to generate a suitable model to study the participation of BDNF in the recovery of the OE after injury in vivo. We developed an experimental design in which the OE of Rhinella arenarum tadpoles could be easily and selectively damaged by immersing the animals in ZnSO(4) solutions of various concentrations for differing time periods. Image analysis of histological sections showed that different combinations of each of these conditions produced statistically different degrees of injury to the olfactory tissue. We also observed that the morphology of the OE was restored within a few days of recovery after ZnSO(4) treatment. Immunohistochemical analysis of BDNF was performed with an antiserum whose specificity was confirmed by Western blotting, and which showed drastic changes in the abundance and distribution pattern of this neurotrophin in the damaged olfactory system. Our results thus suggest that BDNF is involved in the regeneration of the OE of amphibian larvae, and that our approach is suitable for further investigations of this topic. PMID:19221803

  19. Wiring stability of the adult Drosophila olfactory circuit after lesion.

    PubMed

    Berdnik, Daniela; Chihara, Takahiro; Couto, Africa; Luo, Liqun

    2006-03-29

    Neuronal wiring plasticity in response to experience or injury has been reported in many parts of the adult nervous system. For instance, visual or somatosensory cortical maps can reorganize significantly in response to peripheral lesions, yet a certain degree of stability is essential for neuronal circuits to perform their dedicated functions. Previous studies on lesion-induced neuronal reorganization have primarily focused on systems that use continuous neural maps. Here, we assess wiring plasticity in a discrete neural map represented by the adult Drosophila olfactory circuit. Using conditional expression of toxins, we genetically ablated specific classes of neurons and examined the consequences on their synaptic partners or neighboring classes in the adult antennal lobe. We find no alteration of connection specificity between olfactory receptor neurons (ORNs) and their postsynaptic targets, the projection neurons (PNs). Ablating an ORN class maintains PN dendrites within their glomerular borders, and ORN axons normally innervating an adjacent target do not expand. Likewise, ablating PN classes does not alter their partner ORN axon connectivity. Interestingly, an increase in the contralateral ORN axon terminal density occurs in response to the removal of competing ipsilateral ORNs. Therefore, plasticity in this circuit can occur but is confined within a glomerulus, thereby retaining the wiring specificity of ORNs and PNs. We conclude that, although adult olfactory neurons can undergo plastic changes in response to the loss of competition, the olfactory circuit overall is extremely stable in preserving segregated information channels in this discrete map. PMID:16571743

  20. mSWI/SNF (BAF) Complexes Are Indispensable for the Neurogenesis and Development of Embryonic Olfactory Epithelium.

    PubMed

    Bachmann, Christina; Nguyen, Huong; Rosenbusch, Joachim; Pham, Linh; Rabe, Tamara; Patwa, Megha; Sokpor, Godwin; Seong, Rho H; Ashery-Padan, Ruth; Mansouri, Ahmed; Stoykova, Anastassia; Staiger, Jochen F; Tuoc, Tran

    2016-09-01

    Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155 subunit is highly expressed in both oNSCs and ORNs, whereas high expression of BAF170 subunit is observed only in ORNs. We report that conditional deletion of BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs in the developing olfactory epithelium (OE), while the high expression of BAF170 is important for maturation of ORNs. Interestingly, in the absence of BAF complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not specified. Mechanistically, BAF complex is required for normal activation of Pax6-dependent transcriptional activity in stem cells/progenitors of the OE. Our findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE neurogenesis and development. PMID:27611684

  1. Early Olfactory Environment Influences Social Behaviour in Adult Octodon degus

    PubMed Central

    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. PMID:25671542

  2. Adult neurogenesis restores dopaminergic neuronal loss in the olfactory bulb.

    PubMed

    Lazarini, Françoise; Gabellec, Marie-Madeleine; Moigneu, Carine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lledo, Pierre-Marie

    2014-10-22

    Subventricular zone (SVZ) neurogenesis continuously provides new GABA- and dopamine (DA)-containing interneurons for the olfactory bulb (OB) in most adult mammals. DAergic interneurons are located in the glomerular layer (GL) where they participate in the processing of sensory inputs. To examine whether adult neurogenesis might contribute to regeneration after circuit injury in mice, we induce DAergic neuronal loss by injecting 6-hydroxydopamine (6-OHDA) in the dorsal GL or in the right substantia nigra pars compacta. We found that a 6-OHDA treatment of the OB produces olfactory deficits and local inflammation and partially decreases the number of neurons expressing the enzyme tyrosine hydroxylase (TH) near the injected site. Blockade of inflammation by minocycline treatment immediately after the 6-OHDA administration rescued neither TH(+) interneuron number nor the olfactory deficits, suggesting that the olfactory impairments are most likely linked to TH(+) cell death and not to microglial activation. TH(+) interneuron number was restored 1 month later. This rescue resulted at least in part from enhanced recruitment of immature neurons targeting the lesioned GL area. Seven days after 6-OHDA lesion in the OB, we found that the integration of lentivirus-labeled adult-born neurons was biased: newly formed neurons were preferentially incorporated into glomerular circuits of the lesioned area. Behavioral rehabilitation occurs 2 months after lesion. This study establishes a new model into which loss of DAergic cells could be compensated by recruiting newly formed neurons. We propose that adult neurogenesis not only replenishes the population of DAergic bulbar neurons but that it also restores olfactory sensory processing. PMID:25339754

  3. Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors.

    PubMed

    Vannelli, G B; Ensoli, F; Zonefrati, R; Kubota, Y; Arcangeli, A; Becchetti, A; Camici, G; Barni, T; Thiele, C J; Balboni, G C

    1995-06-01

    Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine. In addition, patchclamp experiments reveal that these cells are electrically excitable. Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro. The results suggest that these cells originate from the "stem cell" compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation. PMID:7790915

  4. Expression of polysialyltransferases (STX and PST) in adult rat olfactory bulb after an olfactory associative discrimination task.

    PubMed

    Mione, J; Manrique, C; Duhoo, Y; Roman, F S; Guiraudie-Capraz, G

    2016-04-01

    Neuronal plasticity and neurogenesis occur in the adult hippocampus and in other brain structures such as the olfactory bulb and often involve the neural cell adhesion molecule NCAM. During an olfactory associative discrimination learning task, NCAM polysialylation triggers neuronal plasticity in the adult hippocampus. The PST enzyme likely modulates this polysialylation, but not STX, a second sialyltransferase. How the two polysialyltransferases are involved in the adult olfactory bulb remains unknown. We addressed this question by investigating the effect of olfactory associative learning on plasticity and neurogenesis. After a hippocampo-dependent olfactory associative task learning, we measured the expression of both PST and STX polysialyltransferases in the olfactory bulbs of adult rats using quantitative PCR. In parallel, immunohistochemistry was used to evaluate both NCAM polysialylation level and newly-born cells, with or without learning. After learning, no changes were observed neither in the expression level of PST and NCAM polysialylation, nor in STX gene expression level and newly-born cells number in the olfactory bulb. PMID:26844880

  5. [Action of hyperoxia on the total electrical activity of the olfactory epithelium of the frog].

    PubMed

    Dmitriev, V V; Tarasov, E K; Lukash, A I

    1984-03-01

    Olfactory mucosa of the frog was stimulated with odours of amylacetat , butanol, alcohol, naphthalene, acetic acid in air and oxygen media under normal and high oxygen pressure (0.2 MPa and 0.7 MPa). The electroolfactogram (EOG) amplitude was higher in oxygen due, probably, to the olfactory mucosa oxygen saturation on concentration gradient as well as to the activation of processes related to the EOG generation. 0.2 MPa pressure as well as 0.7 MPa pressure applied for 60 min decreased the EOG amplitude. PMID:6724040

  6. An electroolfactogram study of odor response patterns from the mouse olfactory epithelium with reference to receptor zones and odor sorptiveness.

    PubMed

    Coppola, D M; Waggener, C T; Radwani, S M; Brooks, D A

    2013-04-01

    Olfactory sensory neuron (OSN) responses to odors, measured at the population level, tend to be spatially heterogeneous in the vertebrates that have been studied. These response patterns vary between odors but are similar across subjects for a given stimulus. However, few species have been studied making functional interpretation of these patterns problematic. One proximate explanation for the spatial heterogeneity of odor responses comes from evidence that olfactory receptor (OR) genes in rodents are expressed in OSN populations that are spatially restricted to a few zones in the olfactory epithelium (OE). A long-standing functional explanation for response anisotropy in the OE posits that it is the signature of a supplementary mechanism for quality coding, based on the sorptive properties of odor molecules. These theories are difficult to assess because most mapping studies have utilized few odors, provided little replication, or involved but a single species (rat). In fact, to our knowledge, a detailed olfactory response "map" has not been reported for mouse, the species used in most studies of gene localization. Here we report the results of a study of mouse OE response patterns using the electroolfactogram (EOG). We focused on the medial aspect of olfactory turbinates that are accessible in the midsagittal section. This limited approach still allowed us to test predictions derived from the zonal distribution of OSN types and the sorption hypothesis. In 3 separate experiments, 290 mice were used to record EOGs from a set of standard locations along each of 4 endoturbinates utilizing 11 different odors resulting in over 4,400 separate recordings. Our results confirmed a marked spatial heterogeneity in odor responses that varied with odor, as seen in other species. However, no discontinuities were found in the odor-specific response patterns across the OE as might have been predicted given the existence of classical receptor zones nor did we find clear support

  7. Transduction for Pheromones in the Main Olfactory Epithelium Is Mediated by the Ca2+-Activated Channel TRPM5

    PubMed Central

    López, Fabián; Delgado, Ricardo; López, Roberto; Bacigalupo, Juan

    2014-01-01

    Growing evidence suggests that the main olfactory epithelium contains a subset of olfactory sensory neurons (OSNs) responding to pheromones. One candidate subpopulation expresses the calcium activated cation channel TRPM5 (transient receptor potential channel M5). Using GFP driven by the TRPM5 promoter in mice, we show that this subpopulation responds to putative pheromones, urine, and major histocompatibility complex peptides, but not to regular odors or a pheromone detected by other species. In addition, this subpopulation of TRPM5-GFP+ OSNs uses novel transduction. In regular OSNs, odorants elicit activation of the cyclic nucleotide-gated (CNG) channel, leading to Ca2+ gating of Cl− channels; in TRPM5-GFP+ OSNs, the Ca2+-activated Cl− ANO2 (anoctamin 2) channel is not expressed, and pheromones elicit activation of the CNG channel leading to Ca2+ gating of TRPM5. In conclusion, we show that OSNs expressing TRPM5 respond to pheromones, but not to regular odors through the opening of CNG channels leading to Ca2+ gating of TRPM5. PMID:24573286

  8. De Novo Transcriptomes of Olfactory Epithelium Reveal the Genes and Pathways for Spawning Migration in Japanese Grenadier Anchovy (Coilia nasus)

    PubMed Central

    Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Liu, Dong; Yang, Jinquan

    2014-01-01

    Background Coilia nasus (Japanese grenadier anchovy) undergoes spawning migration from the ocean to fresh water inland. Previous studies have suggested that anadromous fish use olfactory cues to perform successful migration to spawn. However, limited genomic information is available for C. nasus. To understand the molecular mechanisms of spawning migration, it is essential to identify the genes and pathways involved in the migratory behavior of C. nasus. Results Using de novo transcriptome sequencing and assembly, we constructed two transcriptomes of the olfactory epithelium from wild anadromous and non-anadromous C. nasus. Over 178 million high-quality clean reads were generated using Illumina sequencing technology and assembled into 176,510 unigenes (mean length: 843 bp). About 51% (89,456) of the unigenes were functionally annotated using protein databases. Gene ontology analysis of the transcriptomes indicated gene enrichment not only in signal detection and transduction, but also in regulation and enzymatic activity. The potential genes and pathways involved in the migratory behavior were identified. In addition, simple sequence repeats and single nucleotide polymorphisms were analyzed to identify potential molecular markers. Conclusion We, for the first time, obtained high-quality de novo transcriptomes of C. nasus using a high-throughput sequencing approach. Our study lays the foundation for further investigation of C. nasus spawning migration and genome evolution. PMID:25084282

  9. NanoCAGE analysis of the mouse olfactory epithelium identifies the expression of vomeronasal receptors and of proximal LINE elements.

    PubMed

    Pascarella, Giovanni; Lazarevic, Dejan; Plessy, Charles; Bertin, Nicolas; Akalin, Altuna; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J; Zucchelli, Silvia; Kawai, Jun; Daub, Carsten O; Hayashizaki, Yoshihide; Lenhard, Boris; Carninci, Piero; Gustincich, Stefano

    2014-01-01

    By coupling laser capture microdissection to nanoCAGE technology and next-generation sequencing we have identified the genome-wide collection of active promoters in the mouse Main Olfactory Epithelium (MOE). Transcription start sites (TSSs) for the large majority of Olfactory Receptors (ORs) have been previously mapped increasing our understanding of their promoter architecture. Here we show that in our nanoCAGE libraries of the mouse MOE we detect a large number of tags mapped in loci hosting Type-1 and Type-2 Vomeronasal Receptors genes (V1Rs and V2Rs). These loci also show a massive expression of Long Interspersed Nuclear Elements (LINEs). We have validated the expression of selected receptors detected by nanoCAGE with in situ hybridization, RT-PCR and qRT-PCR. This work extends the repertory of receptors capable of sensing chemical signals in the MOE, suggesting intriguing interplays between MOE and VNO for pheromone processing and positioning transcribed LINEs as candidate regulatory RNAs for VRs expression. PMID:24600346

  10. NanoCAGE analysis of the mouse olfactory epithelium identifies the expression of vomeronasal receptors and of proximal LINE elements

    PubMed Central

    Pascarella, Giovanni; Lazarevic, Dejan; Plessy, Charles; Bertin, Nicolas; Akalin, Altuna; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J.; Zucchelli, Silvia; Kawai, Jun; Daub, Carsten O.; Hayashizaki, Yoshihide; Lenhard, Boris; Carninci, Piero; Gustincich, Stefano

    2013-01-01

    By coupling laser capture microdissection to nanoCAGE technology and next-generation sequencing we have identified the genome-wide collection of active promoters in the mouse Main Olfactory Epithelium (MOE). Transcription start sites (TSSs) for the large majority of Olfactory Receptors (ORs) have been previously mapped increasing our understanding of their promoter architecture. Here we show that in our nanoCAGE libraries of the mouse MOE we detect a large number of tags mapped in loci hosting Type-1 and Type-2 Vomeronasal Receptors genes (V1Rs and V2Rs). These loci also show a massive expression of Long Interspersed Nuclear Elements (LINEs). We have validated the expression of selected receptors detected by nanoCAGE with in situ hybridization, RT-PCR and qRT-PCR. This work extends the repertory of receptors capable of sensing chemical signals in the MOE, suggesting intriguing interplays between MOE and VNO for pheromone processing and positioning transcribed LINEs as candidate regulatory RNAs for VRs expression. PMID:24600346

  11. β3GnT2 Maintains Adenylyl Cyclase-3 Signaling and Axon Guidance Molecule Expression in the Olfactory Epithelium

    PubMed Central

    Faden, Ashley A.; Knott, Thomas K.

    2011-01-01

    In the olfactory epithelium (OE), odorant receptor stimulation generates cAMP signals that function in both odor detection and the regulation of axon guidance molecule expression. The enzyme that synthesizes cAMP, adenylyl cyclase 3 (AC3), is coexpressed in olfactory sensory neurons (OSNs) with poly-N-acetyllactosamine (PLN) oligosaccharides determined by the glycosyltransferase β3GnT2. The loss of either enzyme results in similar defects in olfactory bulb (OB) innervation and OSN survival, suggesting that glycosylation may be important for AC3 function. We show here that AC3 is extensively modified with N-linked PLN, which is essential for AC3 activity and localization. On Western blots, AC3 from the wild-type OE migrates diffusely as a heavily glycosylated 200 kDa band that interacts with the PLN-binding lectin LEA. AC3 from the β3GnT2−/− OE loses these PLN modifications, migrating instead as a 140 kDa glycoprotein. Furthermore, basal and forskolin-stimulated cAMP production is reduced 80–90% in the β3GnT2−/− OE. Although AC3 traffics normally to null OSN cilia, it is absent from axon projections that aberrantly target the OB. The cAMP-dependent guidance receptor neuropilin-1 is also lost from β3GnT2−/− OSNs and axons, while semaphorin-3A ligand expression is upregulated. In addition, kirrel2, a mosaically expressed adhesion molecule that functions in axon sorting, is absent from β3GnT2−/− OB projections. These results demonstrate that PLN glycans are essential in OSNs for proper AC3 localization and function. We propose that the loss of cAMP-dependent guidance cues is also a critical factor in the severe axon guidance defects observed in β3GnT2−/− mice. PMID:21525298

  12. Neurogenesis in the vomeronasal epithelium of adult garter snakes: 3. Use of /sup 3/H-thymidine autoradiography to trace the genesis and migration of bipolar neurons

    SciTech Connect

    Wang, R.T.; Halpern, M.

    1988-10-01

    Use of 3H-thymidine autoradiography and unilateral vomeronasal (VN) axotomy has permitted us to demonstrate directly the existence of VN stem cells in the adult garter snake and to trace continuous bipolar neuron development and migration in the normal VN and deafferentated VN epithelium in the same animal. The vomeronasal epithelium and olfactory epithelium of adult garter snakes are both capable of incorporating 3H-thymidine. In the sensory epithelium of the vomeronasal organ, 3H-thymidine-labeled cells were initially restricted to the base of the undifferentiated cell layer in animals surviving 1 day following 3H-thymidine injection. With increasing survival time, labeled cells progressively migrated vertically within the receptor cell column toward the apex of the bipolar neuron layer. In both the normal and denervated VN epithelium, labeled cells were observed through the 56 days of postoperative survival. In the normal epithelium, labeled cells were always located within the matrix of the intact receptor cell columns. However, labeled cells of the denervated epithelium were always located at the apical front of the newly formed cell mass following depletion of the original neuronal cell population. In addition, at postoperative days 28 and 56, labeled cells of the denervated VN epithelium achieved neuronal differentiation and maturation by migrating much farther away from the base of the receptor cell column than the labeled cells on the normal, unoperated contralateral side. This study directly demonstrates that basal cells initially incorporating 3H-thymidine are indeed stem cells of the VN epithelium in adult garter snakes.

  13. Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers

    PubMed Central

    Brus, Maïna; Meurisse, Maryse; Keller, Matthieu; Lévy, Frédéric

    2014-01-01

    New neurons are continuously added in the dentate gyrus (DG) and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the DG was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the postpartum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the DG the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the DG. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor. PMID:24600367

  14. Trpc2-expressing sensory neurons in the mouse main olfactory epithelium of type B express the soluble guanylate cyclase Gucy1b2.

    PubMed

    Omura, Masayo; Mombaerts, Peter

    2015-03-01

    Chemoreception in the mouse olfactory system occurs primarily at two chemosensory epithelia in the nasal cavity: the main olfactory epithelium (MOE) and the vomeronasal epithelium. The canonical chemosensory neurons in the MOE, the olfactory sensory neurons (OSNs), express the odorant receptor (OR) gene repertoire, and depend on Adcy3 and Cnga2 for chemosensory signal transduction. The canonical chemosensory neurons in the vomeronasal epithelium, the vomeronasal sensory neurons (VSNs), express two unrelated vomeronasal receptor (VR) gene repertoires, and involve Trpc2 for chemosensory signal transduction. Recently we reported the discovery of two types of neurons in the mouse MOE that express Trcp2 in addition to Cnga2. These cell types can be distinguished at the single-cell level by expression of Adcy3: positive, type A and negative, type B. Some type A cells express OR genes. Thus far there is no specific gene or marker for type B cells, hampering further analyses such as physiological recordings. Here, we show that among MOE cells, type B cells are unique in their expression of the soluble guanylate cyclase Gucy1b2. We came across Gucy1b2 in an explorative approach based on Long Serial Analysis of Gene Expression (LongSAGE) that we applied to single red-fluorescent cells isolated from whole olfactory mucosa and vomeronasal organ of mice of a novel Trcp2-IRES-taumCherry gene-targeted strain. The generation of a novel Gucy1b2-IRES-tauGFP gene-targeted strain enabled us to visualize coalescence of axons of type B cells into glomeruli in the main olfactory bulb. Our molecular and anatomical analyses define Gucy1b2 as a marker for type B cells within the MOE. The Gucy1b2-IRES-tauGFP strain will be useful for physiological, molecular, cellular, and anatomical studies of this newly described chemosensory subsystem. PMID:25701815

  15. Olfactory Detection Thresholds and Adaptation in Adults with Autism Spectrum Condition

    ERIC Educational Resources Information Center

    Tavassoli, T.; Baron-Cohen, S.

    2012-01-01

    Sensory issues have been widely reported in Autism Spectrum Conditions (ASC). Since olfaction is one of the least investigated senses in ASC, the current studies explore olfactory detection thresholds and adaptation to olfactory stimuli in adults with ASC. 80 participants took part, 38 (18 females, 20 males) with ASC and 42 control participants…

  16. Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium.

    PubMed

    Mistry, Alpesh; Stolnik, Snjezana; Illum, Lisbeth

    2015-08-01

    The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was

  17. Metamorphic remodeling of the olfactory organ of the African clawed frog, Xenopus laevis.

    PubMed

    Dittrich, Katarina; Kuttler, Josua; Hassenklöver, Thomas; Manzini, Ivan

    2016-04-01

    The amphibian olfactory system undergoes massive remodeling during metamorphosis. The transition from aquatic olfaction in larvae to semiaquatic or airborne olfaction in adults requires anatomical, cellular, and molecular modifications. These changes are particularly pronounced in Pipidae, whose adults have secondarily adapted to an aquatic life style. In the fully aquatic larvae of Xenopus laevis, the main olfactory epithelium specialized for sensing water-borne odorous substances lines the principal olfactory cavity (PC), whereas a separate olfactory epithelium lies in the vomeronasal organ (VNO). During metamorphosis, the epithelium of the PC is rearranged into the adult "air nose," whereas a new olfactory epithelium, the adult "water nose," forms in the emerging middle cavity (MC). Here we performed a stage-by-stage investigation of the anatomical changes of the Xenopus olfactory organ during metamorphosis. We quantified cell death in all olfactory epithelia and found massive cell death in the PC and the VNO, suggesting that the majority of larval sensory neurons is replaced during metamorphosis in both sensory epithelia. The moderate cell death in the MC shows that during the formation of this epithelium some cells are sorted out. Our results show that during MC formation some supporting cells, but not sensory neurons, are relocated from the PC to the MC and that they are eventually eliminated during metamorphosis. Together our findings illustrate the structural and cellular changes of the Xenopus olfactory organ during metamorphosis. PMID:26294036

  18. 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. PMID:24797530

  19. Olfactory Enrichment Influences Adult Neurogenesis Modulating GAD67 and Plasticity-Related Molecules Expression in Newborn Cells of the Olfactory Bulb

    PubMed Central

    Peretto, Paolo; Fasolo, Aldo; De Marchis, Silvia

    2009-01-01

    The olfactory bulb (OB) is a highly plastic region of the adult mammalian brain characterized by continuous integration of inhibitory interneurons of the granule (GC) and periglomerular cell (PGC) types. Adult-generated OB interneurons are selected to survive in an experience-dependent way but the mechanisms that mediate the effects of experience on OB neurogenesis are unknown. Here we focus on the new-generated PGC population which is composed by multiple subtypes. Using paradigms of olfactory enrichment and/or deprivation combined to BrdU injections and quantitative confocal immunohistochemical analyses, we studied the effects of olfactory experience on adult-generated PGCs at different survival time and compared PGC to GC modulation. We show that olfactory enrichment similarly influences PGCs and GCs, increasing survival of newborn cells and transiently modulating GAD67 and plasticity-related molecules expression. However, PGC maturation appears to be delayed compared to GCs, reflecting a different temporal dynamic of adult generated olfactory interneuron integration. Moreover, olfactory enrichment or deprivation do not selectively modulate the survival of specific PGC phenotypes, supporting the idea that the integration rate of distinct PGC subtypes is independent from olfactory experience. PMID:19626121

  20. Neuropeptide Y in the olfactory microvillar cells.

    PubMed

    Montani, Giorgia; Tonelli, Simone; Elsaesser, Rebecca; Paysan, Jacques; Tirindelli, Roberto

    2006-07-01

    This paper examines a possible role of microvillar cells in coordinating cell death and regeneration of olfactory epithelial neurons. The olfactory neuroepithelium of mammals is a highly dynamic organ. Olfactory neurons periodically degenerate by apoptosis and as a consequence of chemical or physical damage. To compensate for this loss of cells, the olfactory epithelium maintains a lifelong ability to regenerate from a pool of resident multipotent stem cells. To assure functional continuity and histological integrity of the olfactory epithelium over a period of many decades, apoptosis and regeneration require to be precisely coordinated. Among the factors that have been implicated in mediating this regulation is the neuropeptide Y (NPY). Knockout mice that lack functional expression of this neurogenic peptide show defects in embryonic development of the olfactory epithelium and in its ability to regenerate in the adult. Here we show that, in postnatal olfactory epithelia, NPY is exclusively expressed by a specific population of microvillar cells. We previously characterized these cells as a novel type of putative chemosensory cells, which are provided with a phosphatidyl-inositol-mediated signal transduction cascade. Our findings allow for the first time to suggest that microvillar cells are involved in connecting apoptosis to neuronal regeneration by stimulus-induced release of NPY. PMID:16800866

  1. Seasonal changes in the histochemical properties of the olfactory epithelium and vomeronasal organ in the Japanese striped snake, Elaphe quadrivirgata.

    PubMed

    Kondoh, D; Yamamoto, Y; Nakamuta, N; Taniguchi, K; Taniguchi, K

    2012-02-01

    Seasonal changes in the histochemical properties of the vomeronasal and olfactory epithelia of the Japanese striped snake were examined in four seasons, viz. the reproductive, pre-hibernating, hibernating and post-hibernating seasons. In the vomeronasal and olfactory supporting cells, secretory granules were much more abundant in the hibernating season than in the other seasons. In the vomeronasal and olfactory receptor cells, the lipofuscin granules were much fewer in the post-hibernating season than in the other seasons. In histochemical studies with 21 lectins, several lectins stained the vomeronasal and olfactory epithelia (receptor cells, supporting cells and free border) more weakly in the hibernating season than in the reproductive season. However, all lectins stained both epithelia in the hibernating season after sialic acid removal in a similar manner as in the reproductive season after sialic acid removal. These lectin histochemical studies indicate that sialic acid residues in the vomeronasal and olfactory epithelia are more numerous in the hibernating season than in the reproductive season. The results suggest that during hibernation, the vomeronasal and olfactory receptor cells possibly undergo rapid cell turnover, and that during this time, the vomeronasal and olfactory epithelia are securely protected from pathogens by an innate immune defence system. PMID:21895741

  2. Id2 IS REQUIRED FOR SPECIFICATION OF DOPAMINERGIC NEURONS DURING ADULT OLFACTORY NEUROGENESIS

    PubMed Central

    Havrda, Matthew C.; Harris, Brent T.; Mantani, Akio; Ward, Nora M.; Paolella, Brenton R.; Cuzon, Verginia C.; Yeh, Hermes H.; Israel, Mark A.

    2009-01-01

    Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking Inhibitor of DNA Binding 2 (Id2). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2−/− mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Mash1 transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals. PMID:19109490

  3. Dietary intakes of fats, fish and nuts and olfactory impairment in older adults.

    PubMed

    Gopinath, Bamini; Sue, Carolyn M; Flood, Victoria M; Burlutsky, George; Mitchell, Paul

    2015-07-01

    It is unclear whether lifestyle modifications, such as dietary changes, should be advocated to prevent olfactory dysfunction. We investigated the association between dietary intakes of fats (saturated, mono-unsaturated and polyunsaturated fats, and cholesterol) and related food groups (nuts, fish, butter, margarine) with olfactory impairment. There were 1331 and 667 participants (older than 60 years) at baseline and 5-year follow-up, respectively, with complete olfaction and dietary data. Dietary data were collected using a validated semi-quantitative FFQ. Olfaction was measured using the San Diego Odor Identification Test. In a cross-sectional analysis of baseline data, those in the highest v. lowest quartile of n-6 PUFA intake had reduced odds of having any olfactory impairment, multivariable-adjusted OR 0.66 (95% CI 0.44, 0.97), P for trend = 0.06. Participants in the highest v. lowest quartile of margarine consumption had a 65% reduced odds of having moderate/severe olfactory impairment (P for trend = 0.02). Participants in the highest quartile compared to the lowest quartile (reference) of nut consumption had a 46% (P for trend = 0.01) and 58% (P for trend = 0.001) reduced odds of having any or mild olfactory impairment, respectively. Older adults in the highest v. lowest quartile of fish consumption had 35% (P for trend = 0.03) and 50% (P for trend = 0.01) reduced likelihood of having any or mild olfactory impairment, respectively. In longitudinal analyses, a marginally significant association was observed between nut consumption and incidence of any olfactory impairment, highest v. lowest quartile of nut consumption: OR 0.61 (95% CI 0.37, 1.00). Older adults with the highest consumption of nuts and fish had reduced odds of olfactory impairment, independent of potential confounding variables. PMID:26079067

  4. Identification of Distinct Layers Within the Stratified Squamous Epithelium of the Adult Human True Vocal Fold

    PubMed Central

    Dowdall, Jayme R.; Sadow, Peter M.; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C.; Franco, Ramon A.; Rajagopal, Jayaraj

    2016-01-01

    Objectives/Hypothesis A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study Design Qualitative study with adult human larynges. Methods Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). Results We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. Conclusion We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of Evidence N/A. PMID:25988619

  5. The impact of adult neurogenesis on olfactory bulb circuits and computations.

    PubMed

    Lepousez, Gabriel; Valley, Matthew T; Lledo, Pierre-Marie

    2013-01-01

    Modern neuroscience has demonstrated how the adult brain has the ability to profoundly remodel its neurons in response to changes in external stimuli or internal states. However, adult brain plasticity, although possible throughout life, remains restricted mostly to subcellular levels rather than affecting the entire cell. New neurons are continuously generated in only a few areas of the adult brain-the olfactory bulb and the dentate gyrus-where they integrate into already functioning circuitry. In these regions, adult neurogenesis adds another dimension of plasticity that either complements or is redundant to the classical molecular and cellular mechanisms of plasticity. This review extracts clues regarding the contribution of adult-born neurons to the different circuits of the olfactory bulb and specifically how new neurons participate in existing computations and enable new computational functions. PMID:23190074

  6. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  7. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors.

    PubMed

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  8. Selective Viral Transduction of Adult-born Olfactory Neurons for Chronic in vivo Optogenetic Stimulation

    PubMed Central

    Lepousez, Gabriel; Alonso, Mariana; Wagner, Sebastian; Gallarda, Benjamin W.; Lledo, Pierre-Marie

    2011-01-01

    Local interneurons are continuously regenerated in the olfactory bulb of adult rodents1-3. In this process, called adult neurogenesis, neural stem cells in the walls of the lateral ventricle give rise to neuroblasts that migrate for several millimeters along the rostral migratory stream (RMS) to reach and incorporate into the olfactory bulb. To study the different steps and the impact of adult-born neuron integration into preexisting olfactory circuits, it is necessary to selectively label and manipulate the activity of this specific population of neurons. The recent development of optogenetic technologies offers the opportunity to use light to precisely activate this specific cohort of neurons without affecting surrounding neurons4,5. Here, we present a series of procedures to virally express Channelrhodopsin2(ChR2)-YFP in a temporally restricted cohort of neuroblasts in the RMS before they reach the olfactory bulb and become adult-born neurons. In addition, we show how to implant and calibrate a miniature LED for chronic in vivo stimulation of ChR2-expressing neurons. PMID:22231709

  9. [Differentially expressed genes identified in the main olfactory epithelium of mice with deficiency of adenylate cyclase 3 by using suppression subtractive hybridization approach].

    PubMed

    Zhenlong, Cao; Jiangye, Hao; Yanfen, Zhou; Zhe, Zhang; Zhihua, Ni; Yuanxiang, Hu; Weili, Liu; Yongchao, Li; Daniel, R Storm; Runlin, Z Ma; Zhenshan, Wang

    2014-06-01

    Adenylate cyclase 3 (AC3) is one of the major players in the olfactory signaling within the main olfactory epithelium (MOE) of mice. However, we are not ascertained whether deficiency of AC3 will lead to the differential expression of related genes in the MOE. Forward and reverse subtractive libraries were constructed by suppression subtractive hybridization (SSH) approach, with MOEs from AC3(-/-) and AC3(+/+) mice. These two libraries were primarily screened by Dot blot, differential expressed clones were sequenced and analyzed by bioinformatics, and differential expressed genes were verified by qRT-PCR. A total of 386 differentially expressed clones were picked out after Dot blot. The DNA sequences of 80 clones randomly selected were determined, and 62 clones were identified by blasting in GenBank. We found that 24 up-regulated clones were corresponded to genes of kcnk3, mapk7, megf11, and 38 down-regulated clones were corresponded to tmem88b, c-mip, skp1a, mlycd, etc. Their functions were annotated with Gene Ontology (GO) and found to be mainly focused on molecular binding, cell cycle, processes of biology and cells. Five genes (kcnk3, c-mip, mlycd, tmem88b and trappc5) were verified by qRT-PCR with individuals of AC3(+/+) and AC3(-/-) mice. The data indicate that kcnk3 gene is up-regulated significantly, increasing 1.27 folds compared to control mice, whereas c-mip, mlycd, tmem88b and trappc5 are down-regulated significantly, decreasing 20%, 7%, 32% and 29% compared to the AC3(+/+)mice. The functions of these genes are closely related with K(+) channels, cell differentiation, metabolism of fats, membrane transportation, and so on. It is tempting to speculate that these genes might work together with AC3 to orchestrate the olfactory transduction signaling in the MOE. PMID:24929516

  10. Relationship between olfactory and visual stimuli during host plant recognition in immature and adult glassy-winged sharpshooter.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An olfactometer was designed to assess the relative effects of visual, olfactory, and visual x olfactory stimuli on host plant detection in adult and immature glassy-winged sharpshooter, Homalodisca coagulata. Factorial designs were used in no-choice tests to measure responses to binary combination...

  11. Disruption of Adult Neurogenesis in the Olfactory Bulb Affects Social Interaction but not Maternal Behavior

    PubMed Central

    Feierstein, Claudia E.; Lazarini, Françoise; Wagner, Sebastien; Gabellec, Marie-Madeleine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Boussin, François D.; Lledo, Pierre-Marie; Gheusi, Gilles

    2010-01-01

    Adult-born neurons arrive to the olfactory bulb (OB) and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of factors, notably by instances related to reproductive behavior, such as exposure to mating partners, pregnancy and lactation, and exposure to offspring. To study the contribution of olfactory neurogenesis to maternal behavior and social recognition, here we selectively disrupted OB neurogenesis using focal irradiation of the subventricular zone in adult female mice. We show that reduction of olfactory neurogenesis results in an abnormal social interaction pattern with male, but not female, conspecifics; we suggest that this effect could result from the inability to detect or discriminate male odors and could therefore have implications for the recognition of potential mating partners. Disruption of OB neurogenesis, however, neither impaired maternal-related behaviors, nor did it affect the ability of mothers to discriminate their own progeny from others. PMID:21160552

  12. Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity

    PubMed Central

    Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia

    2016-01-01

    The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651

  13. Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity.

    PubMed

    Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia

    2016-01-01

    The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651

  14. Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

    PubMed

    Herrera, Loren P; Casas, Carlos E; Bates, Margaret L; Guest, James D

    2005-08-01

    Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates. PMID:15973683

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

    PubMed Central

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

    2012-01-01

    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 non-cell 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. PMID:22648855

  16. 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. PMID:22648855

  17. The interplay between reproductive social stimuli and adult olfactory bulb neurogenesis.

    PubMed

    Peretto, Paolo; Schellino, Roberta; De Marchis, Silvia; Fasolo, Aldo

    2014-01-01

    Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition. PMID:25140258

  18. The Interplay between Reproductive Social Stimuli and Adult Olfactory Bulb Neurogenesis

    PubMed Central

    De Marchis, Silvia; Fasolo, Aldo

    2014-01-01

    Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition. PMID:25140258

  19. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage

    PubMed Central

    Fernandez Vallone, Valeria; Leprovots, Morgane; Strollo, Sandra; Vasile, Gabriela; Lefort, Anne; Libert, Frederick; Vassart, Gilbert; Garcia, Marie-Isabelle

    2016-01-01

    ABSTRACT Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2+ cells generating gastric spheroids differed from adult glandular Lgr5+ stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5+ stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2+ cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2+ cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program. PMID:26989172

  20. 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. PMID:25933936

  1. From progenitors to integrated neurons: role of neurotransmitters in adult olfactory neurogenesis.

    PubMed

    Bovetti, Serena; Gribaudo, Simona; Puche, Adam C; De Marchis, Silvia; Fasolo, Aldo

    2011-12-01

    Adult neurogenesis is due to the persistence of pools of constitutive stem cells able to give rise to a progeny of proliferating progenitors. In rodents, adult neurogenic niches have been found in the subventricular zone (SVZ) along the lateral ventricles and in the subgranular zone of the dentate gyrus in the hippocampus. SVZ progenitors undergo a unique process of tangential migration from the lateral ventricle to the olfactory bulb (OB) where they differentiate mainly into GABAergic interneurons in the granule and glomerular layers. SVZ progenitor proliferation, migration and differentiation into fully integrated neurons, are strictly related processes regulated by complex interactions between cell intrinsic and extrinsic influences. Numerous observations demonstrate that neurotrasmitters are involved in all steps of the adult neurogenic process, but the understanding of their role is hampered by their intricate mechanism of action and by the highly complex network in which neurotransmitters work. By considering the three main steps of olfactory adult neurogenesis (proliferation, migration and integration), this review will discuss recent advances in the study of neurotransmitters, highlighting the regulatory mechanisms upstream and downstream their action. PMID:21641990

  2. Expression of stathmin and SCG10 proteins in the olfactory neurogenesis during development and after lesion in the adulthood.

    PubMed

    Camoletto, P; Colesanti, A; Ozon, S; Sobel, A; Fasolo, A

    2001-01-01

    Stathmin and SCG10 belong to a family of phosphoproteins associated to cell proliferation and differentiation. In the present study, we have analyzed immunocytochemically the distribution of these proteins during neurogenesis in the mouse olfactory system, from midgestation to adulthood. Data show that already at embryonic day 12, stathmin and SCG10 immunoreactivities were present in the olfactory and vomeronasal neurons, and their number increased greatly, colocalizing with neuronal specific tubulin, a marker of immature neurons. Later on up to adulthood, the distribution of stathmin and SCG10 became progressively restricted to a few immature receptor and chemosensory neurons. Significantly, in the olfactory epithelium, stathmin was seen in immature neurons and also in basal cells representing precursors of neuronal elements. Interestingly, before birth stathmin and SCG10 immunopositive cells were seen outside the olfactory epithelium, seemingly migrating toward the olfactory bulb. After regeneration in the adult following peripheral lesion of the olfactory epithelium, stathmin and SCG10 were again strongly expressed and generally colocalized with neuronal specific tubulin immunoreactivity. Overall these results indicate that stathmin and SCG10 are expressed in immature olfactory neurons as well as in the migrating cells generated from the olfactory epithelium, supporting the role of these proteins in neurogenesis and cell migration. PMID:11226711

  3. Mitral cells in the olfactory bulb of adult zebrafish (Danio rerio): morphology and distribution.

    PubMed

    Fuller, Cynthia L; Yettaw, Holly K; Byrd, Christine A

    2006-11-10

    The mitral cell is the primary output neuron and central relay in the olfactory bulb of vertebrates. The morphology of these cells has been studied extensively in mammalian systems and to a lesser degree in teleosts. This study uses retrograde tract tracing and other techniques to characterize the morphology and distribution of mitral cells in the olfactory bulb of adult zebrafish, Danio rerio. These output neurons, located primarily in the glomerular layer and superficial internal cell layer, had variable-shaped somata that ranged in size from 4-18 microm in diameter and 31-96 microm2 in cross-sectional area. The mitral cells exhibited two main types of morphologies with regard to their dendrites: the unidendritic morphology was a single primary dendrite with one or more tufts, but multidendritic cells with several dendritic projections also were seen. The axons of these cells projected to either the medial or the lateral olfactory tract and, in general, the location of the cell on the medial or lateral side of the bulb was indicative of the tract to which it would project. Further, this study shows that the majority of zebrafish mitral cells likely innervate a single glomerulus rather than multiple glomeruli. This information is contrary to the multiple innervation pattern suggested for all teleost mitral cells. Our findings suggest that mitral cells in zebrafish may be more similar to mammalian mitral cells than previously believed, despite variation in size and structure. This information provides a revised anatomical framework for olfactory processing studies in this key model system. PMID:16977629

  4. A Comparison of the Olfactory Gene Repertoires of Adults and Larvae in the Noctuid Moth Spodoptera littoralis

    PubMed Central

    Poivet, Erwan; Gallot, Aurore; Montagné, Nicolas; Glaser, Nicolas; Legeai, Fabrice; Jacquin-Joly, Emmanuelle

    2013-01-01

    To better understand the olfactory mechanisms in a lepidopteran pest model species, the cotton leafworm Spodoptera littoralis, we have recently established a partial transcriptome from adult antennae. Here, we completed this transcriptome using next generation sequencing technologies, namely 454 and Illumina, on both adult antennae and larval tissues, including caterpillar antennae and maxillary palps. All sequences were assembled in 77,643 contigs. Their analysis greatly enriched the repertoire of chemosensory genes in this species, with a total of 57 candidate odorant-binding and chemosensory proteins, 47 olfactory receptors, 6 gustatory receptors and 17 ionotropic receptors. Using RT-PCR, we conducted the first exhaustive comparison of olfactory gene expression between larvae and adults in a lepidopteran species. All the 127 candidate olfactory genes were profiled for expression in male and female adult antennae and in caterpillar antennae and maxillary palps. We found that caterpillars expressed a smaller set of olfactory genes than adults, with a large overlap between these two developmental stages. Two binding proteins appeared to be larvae-specific and two others were adult-specific. Interestingly, comparison between caterpillar antennae and maxillary palps revealed numerous organ-specific transcripts, suggesting the complementary involvement of these two organs in larval chemosensory detection. Adult males and females shared the same set of olfactory transcripts, except two male-specific candidate pheromone receptors, two male-specific and two female-specific odorant-binding proteins. This study identified transcripts that may be important for sex-specific or developmental stage-specific chemosensory behaviors. PMID:23565215

  5. Patterns of olfactory bulb neurogenesis in the adult zebrafish are altered following reversible deafferentation.

    PubMed

    Trimpe, Darcy M; Byrd-Jacobs, Christine A

    2016-09-01

    Adult brain plasticity can be investigated using reversible methods that remove afferent innervation but allow return of sensory input. Repeated intranasal irrigation with Triton X-100 in adult zebrafish diminishes innervation to the olfactory bulb, resulting in a number of alterations in bulb structure and function, and cessation of the treatment allows for reinnervation and recovery. Using bromodeoxyuridine, Hu, and caspase-3 immunoreactivity we examined cell proliferation, differentiation, migration, and survival under conditions of acute and chronic deafferentation and reafferentation. Cell proliferation within the olfactory bulb was not influenced by acute or chronic deafferentation or reafferentation, but cell fate (including differentiation, migration, and/or survival of newly formed cells) was affected. We found that chronic deafferentation caused a bilateral increase in the number of newly formed cells that migrated into the bulb, although the amount of cell death of these new cells was significantly increased compared to untreated fish. Reafferentation also increased the number of newly formed cells migrating into both bulbs, suggesting that the deafferentation effect on cell fate was maintained. Reafferentation resulted in a decrease in newly formed cells that became neurons and, although death of newly formed cells was not altered from control levels, survival was reduced in relation to that seen in chronically deafferented fish. The potential effect of age on cell genesis was also examined. While the amount of cell migration into the olfactory bulbs was not affected by fish age, more of the newly formed cells became neurons in older fish. Younger fish displayed more cell death under conditions of chronic deafferentation. In sum, our results show that reversible deafferentation affects several aspects of cell fate, including cell differentiation, migration, and survival, and age of the fish influences the response to deafferentation. PMID:27343831

  6. Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization.

    PubMed

    Polese, Gianluca; Bertapelle, Carla; Di Cosmo, Anna

    2016-01-01

    The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens. PMID:27069253

  7. Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

    PubMed Central

    Polese, Gianluca; Bertapelle, Carla

    2016-01-01

    ABSTRACT The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens. PMID:27069253

  8. The role of the olfactory recess in olfactory airflow.

    PubMed

    Eiting, Thomas P; Smith, Timothy D; Perot, J Blair; Dumont, Elizabeth R

    2014-05-15

    The olfactory recess - a blind pocket at the back of the nasal airway - is thought to play an important role in mammalian olfaction by sequestering air outside of the main airstream, thus giving odorants time to re-circulate. Several studies have shown that species with large olfactory recesses tend to have a well-developed sense of smell. However, no study has investigated how the size of the olfactory recess relates to air circulation near the olfactory epithelium. Here we used a computer model of the nasal cavity from a bat (Carollia perspicillata) to test the hypothesis that a larger olfactory recess improves olfactory airflow. We predicted that during inhalation, models with an enlarged olfactory recess would have slower rates of flow through the olfactory region (i.e. the olfactory recess plus airspace around the olfactory epithelium), while during exhalation these models would have little to no flow through the olfactory recess. To test these predictions, we experimentally modified the size of the olfactory recess while holding the rest of the morphology constant. During inhalation, we found that an enlarged olfactory recess resulted in lower rates of flow in the olfactory region. Upon exhalation, air flowed through the olfactory recess at a lower rate in the model with an enlarged olfactory recess. Taken together, these results indicate that an enlarged olfactory recess improves olfactory airflow during both inhalation and exhalation. These findings add to our growing understanding of how the morphology of the nasal cavity may relate to function in this understudied region of the skull. PMID:24577441

  9. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network

    PubMed Central

    Malvaut, Sarah; Saghatelyan, Armen

    2016-01-01

    The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID:26839709

  10. The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

    PubMed Central

    Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

    2016-01-01

    In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

  11. The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb.

    PubMed

    Gengatharan, Archana; Bammann, Rodrigo R; Saghatelyan, Armen

    2016-01-01

    In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

  12. Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb.

    PubMed

    Bonzano, Sara; Bovetti, Serena; Fasolo, Aldo; Peretto, Paolo; De Marchis, Silvia

    2014-11-01

    The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information. PMID:25216299

  13. COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons.

    PubMed

    Bovetti, Serena; Bonzano, Sara; Garzotto, Donatella; Giannelli, Serena Gea; Iannielli, Angelo; Armentano, Maria; Studer, Michèle; De Marchis, Silvia

    2013-12-01

    COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons. PMID:24227652

  14. Detection of alpha-L fucose containing carbohydrates in mouse immature olfactory neurons.

    PubMed

    Ducray, A; Propper, A; Kastner, A

    1999-10-15

    The cellular location of alpha-L fucose was studied in mice olfactory epithelium (OE) using the Ulex europaeus agglutinin-I (UEA-I) and Tetragonolobus purpureas agglutinin (TPA). In adult mice, UEA-I and TPA revealed a layer of cells that mostly correspond to immature olfactory neurons. Moreover, autoradiographic studies after 3H-T incorporation showed that UEA-I cell labelling occurred during the week following the division of neural cell precursors. In newborn animals, active neurogenesis process is associated with a higher number of UEA-I labelled cells. Olfactory neurogenesis may thus involve a transient event of protein fucosylation, preceding axonal growth. PMID:10530509

  15. Flexible responses to visual and olfactory stimuli by foraging Manduca sexta: larval nutrition affects adult behaviour

    PubMed Central

    Goyret, Joaquín; Kelber, Almut; Pfaff, Michael; Raguso, Robert A.

    2009-01-01

    Here, we show that the consequences of deficient micronutrient (β-carotene) intake during larval stages of Manduca sexta are carried across metamorphosis, affecting adult behaviour. Our manipulation of larval diet allowed us to examine how developmental plasticity impacts the interplay between visual and olfactory inputs on adult foraging behaviour. Larvae of M. sexta were reared on natural (Nicotiana tabacum) and artificial laboratory diets containing different concentrations of β-carotene (standard diet, low β-carotene, high β-carotene and cornmeal). This vitamin-A precursor has been shown to be crucial for photoreception sensitivity in the retina of M. sexta. After completing development, post-metamorphosis, starved adults were presented with artificial feeders that could be either scented or unscented. Regardless of their larval diet, adult moths fed with relatively high probabilities on scented feeders. When feeders were unscented, moths reared on tobacco were more responsive than moths reared on β-carotene-deficient artificial diets. Strikingly, moths reared on artificial diets supplemented with increasing amounts of β-carotene (low β and high β) showed increasing probabilities of response to scentless feeders. We discuss these results in relationship to the use of complex, multi-modal sensory information by foraging animals. PMID:19419987

  16. Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb

    PubMed Central

    Naser, Rayan; Vandenbosch, Renaud; Omais, Saad; Hayek, Dayana; Jaafar, Carine; Al Lafi, Sawsan; Saliba, Afaf; Baghdadi, Maarouf; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons. PMID:26847607

  17. Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb.

    PubMed

    Naser, Rayan; Vandenbosch, Renaud; Omais, Saad; Hayek, Dayana; Jaafar, Carine; Al Lafi, Sawsan; Saliba, Afaf; Baghdadi, Maarouf; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons. PMID:26847607

  18. Search behavior in various breeds of adult dogs (Canis familiaris): object permanence and olfactory cues.

    PubMed

    Gagnon, S; Doré, F Y

    1992-03-01

    Human analog tests of object permanence were administered to various breeds of adult dogs (Canis familiaris). Experiment 1 showed that the performance of terriers, sporting, and working dogs did not differ. Dogs succeeded in solving invisible displacement problems, but performance was lower than in visible displacement tests. Familiarity with the task had some influence because invisible displacement tests were more successful if they were preceded by visible displacement tests. In Experiment 2, odor cues from the target object and the hiding screens were available or were masked. Results confirmed that success was lower in invisible than in visible displacement tests and that these problems were solved on the basis of representation of visual information rather than on the basis of olfactory cues or of local rule learning. Dogs are compared with other species that display Stage 6 object permanence. PMID:1365009

  19. 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…

  20. Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size.

    PubMed

    Morrison, Filomene G; Dias, Brian G; Ressler, Kerry J

    2015-10-13

    Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training. PMID:26420875

  1. Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

    PubMed Central

    Morrison, Filomene G.; Dias, Brian G.; Ressler, Kerry J.

    2015-01-01

    Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training. PMID:26420875

  2. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  3. Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb.

    PubMed

    Breton-Provencher, Vincent; Bakhshetyan, Karen; Hardy, Delphine; Bammann, Rodrigo Roberto; Cavarretta, Francesco; Snapyan, Marina; Côté, Daniel; Migliore, Michele; Saghatelyan, Armen

    2016-01-01

    Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing. PMID:27578235

  4. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    PubMed Central

    Bagley, Joshua; LaRocca, Greg; Jimenez, Daniel A; Urban, Nathaniel N

    2007-01-01

    Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA) and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival. PMID:17996088

  5. Differential expression of TYRP1 in adult human retinal pigment epithelium and uveal melanoma cells

    PubMed Central

    QIU, CHUN; LI, PENG; BI, JIANJUN; WU, QING; LU, LINNA; QIAN, GUANXIANG; JIA, RENBING; JIA, RONG

    2016-01-01

    Uveal melanoma (UM) is the most frequently occurring primary intraocular malignancy in adults. Tyrosinase (TYR) is a copper-containing enzyme and a type I membrane protein that is involved in the generation of melanin, the main pigment in vertebrates. TYR-related protein 1 (TYRP1) is regarded to have a crucial role in the immunotherapy of melanoma. As biomarkers, the TYR-related proteins, TYRP1 and TYRP2, exhibit specific expression in melanocytes, while also contributing to melanin synthesis within melanosomes. In the present study, the differential expression of TYRP1 was investigated at the mRNA, protein and morphological levels in four human UM cell lines (SP6.5, OM431, OCM1 and OCM290) and the human retinal pigment epithelium (RPE) cell line, using polymerase chain reaction, western blotting, immunocytochemistry and immunofluorescence staining. It was found that SP6.5 cells expressed the highest level of TYRP1, in comparison to SP6.5 OCM1 and OM431 cells, which produced less TYRP1, and OCM290 cells, which produced almost no TYRP1. No TYRP1 protein expression was identified in the RPE cell line. These findings indicate the potential use of TYRP1 in the development of therapy for UM. PMID:27073483

  6. A lifetime of neurogenesis in the olfactory system.

    PubMed

    Brann, Jessica H; Firestein, Stuart J

    2014-01-01

    Neurogenesis continues well beyond embryonic and early postnatal ages in three areas of the nervous system. The subgranular zone supplies new neurons to the dentate gyrus of the hippocampus. The subventricular zone supplies new interneurons to the olfactory bulb, and the olfactory neuroepithelia generate new excitatory sensory neurons that send their axons to the olfactory bulb. The latter two areas are of particular interest as they contribute new neurons to both ends of a first-level circuit governing olfactory perception. The vomeronasal organ and the main olfactory epithelium comprise the primary peripheral olfactory epithelia. These anatomically distinct areas share common features, as each exhibits extensive neurogenesis well beyond the juvenile phase of development. Here we will discuss the effect of age on the structural and functional significance of neurogenesis in the vomeronasal and olfactory epithelia, from juvenile to advanced adult ages, in several common model systems. We will next discuss how age affects the regenerative capacity of these neural stem cells in response to injury. Finally, we will consider the integration of newborn neurons into an existing circuit as it is modified by the age of the animal. PMID:25018692

  7. Olfactory marker protein: turnover and transport in normal and regenerating neurons

    SciTech Connect

    Kream, R.M.; Margolis, F.L.

    1984-03-01

    A 19,000-dalton acidic protein designated olfactory marker protein (OMP) is a cell-specific marker of mature olfactory chemosensory neurons. Intranasal irrigation of mouse olfactory epithelium with (/sup 35/S)methionine labeled OMP to high specific activity. Turnover and transport characteristics of /sup 35/S-labeled OMP were compared to those of /sup 35/S-labeled global cytosol protein in groups of young, adult, and Triton-treated adult mice. The latter contained primarily large numbers of regenerating olfactory neurons. In olfactory epithelium of young and Triton-treated mice, the specific activity of OMP was three times that of global cytosol protein, whereas in adults the two measures were equal. In all three groups, however, the rate of degradation of OMP was roughly equal to that of cytosol protein (T1/2 . 5 to 6 days). By contrast, differences in T1/2 for OMP decline in the bulb of adult, young, and Triton-treated adult mice were highly significant (T1/2's of 9.3, 6.1, and 4 to 5 days, respectively; p . 0.001). The specific activity of (35S)methionine incorporated in OMP exceeded that of the free amino acid 5-fold, indicating minimal precursor reutilization during the course of our experiments. Turnover data indicate that increased isotope incorporation into OMP in the epithelium is matched by an accelerated rate of degradation in the bulb. This may be correlated with the physiological state or developmental age of the primary neurons since in young and Triton-treated adult mice, rapidly maturing ''young'' olfactory neurons represent a larger proportion of the total population than in adults. Thus, OMP behaves as a typical, relatively slowly transported soluble protein (v . 2 to 4 mm/day, slow component b).

  8. Influence of Dietary Experience on the Induction of Preference of Adult Moths and Larvae for a New Olfactory Cue

    PubMed Central

    Petit, Christophe; Le Ru, Bruno; Dupas, Stéphane; Frérot, Brigitte; Ahuya, Peter; Kaiser-Arnauld, Laure; Harry, Myriam; Calatayud, Paul-André

    2015-01-01

    In Lepidoptera, host plant selection is first conditioned by oviposition site preference of adult females followed by feeding site preference of larvae. Dietary experience to plant volatile cues can induce larval and adult host plant preference. We investigated how the parent’s and self-experience induce host preference in adult females and larvae of three lepidopteran stem borer species with different host plant ranges, namely the polyphagous Sesamia nonagrioides, the oligophagous Busseola fusca and the monophagous Busseola nairobica, and whether this induction can be linked to a neurophysiological phenotypic plasticity. The three species were conditioned to artificial diet enriched with vanillin from the neonate larvae to the adult stage during two generations. Thereafter, two-choice tests on both larvae and adults using a Y-tube olfactometer and electrophysiological (electroantennography [EAG] recordings) experiments on adults were carried out. In the polyphagous species, the induction of preference for a new olfactory cue (vanillin) by females and 3rd instar larvae was determined by parents’ and self-experiences, without any modification of the sensitivity of the females antennae. No preference induction was found in the oligophagous and monophagous species. Our results suggest that lepidopteran stem borers may acquire preferences for new olfactory cues from the larval to the adult stage as described by Hopkins’ host selection principle (HHSP), neo-Hopkins’ principle, and the concept of ‘chemical legacy.’ PMID:26288070

  9. A neonicotinoid impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults

    PubMed Central

    Tan, Ken; Chen, Weiwen; Dong, Shihao; Liu, Xiwen; Wang, Yuchong; Nieh, James C.

    2015-01-01

    Xenobiotics such as the neonicotinoid pesticide, imidacloprid, are used globally, but their effects on native bee species are poorly understood. We studied the effects of sublethal doses of imidacloprid on olfactory learning in the native honey bee species, Apis cerana, an important pollinator of agricultural and native plants throughout Asia. We provide the first evidence that imidacloprid can impair learning in A. cerana workers exposed as adults or as larvae. Adults that ingested a single imidacloprid dose as low as 0.1 ng/bee had significantly reduced olfactory learning acquisition, which was 1.6-fold higher in control bees. Longer-term learning (1-17 h after the last learning trial) was also impaired. Bees exposed as larvae to a total dose of 0.24 ng/bee did not have reduced survival to adulthood. However, these larval-treated bees had significantly impaired olfactory learning when tested as adults: control bees exhibited up to 4.8-fold better short-term learning acquisition, though longer-term learning was not affected. Thus, sublethal cognitive deficits elicited by neonicotinoids on a broad range of native bee species deserve further study. PMID:26086769

  10. Fragile X Mental Retardation Protein Regulates New Neuron Differentiation in the Adult Olfactory Bulb

    PubMed Central

    Scotto-Lomassese, Sophie; Nissant, Antoine; Mota, Tatiana; Néant-Féry, Marie; Oostra, Ben A.; Greer, Charles A.; Lledo, Pierre-Marie; Trembleau, Alain; Caillé, Isabelle

    2013-01-01

    The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in the Fmr1 knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in the Fmr1 KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutate Fmr1 in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis. PMID:21307257

  11. Reduced olfactory bulb volume in adults with a history of childhood maltreatment.

    PubMed

    Croy, Ilona; Negoias, Simona; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Hummel, Thomas

    2013-10-01

    The human olfactory bulb (OB) is the first relay station of the olfactory pathway and may have the potential for postnatal neurogenesis in early childhood. In animals, chronic stress affects the OB and olfactory functioning. For humans, it has been shown that major depressive disorder is accompanied by reduced OB volume and reduced olfactory function. However, it is not clear if major stress in childhood development also affects olfactory functioning and OB volume in humans. OB volume was measured and olfactory function was tested in 17 depressive patients with and 10 without a history of severe childhood maltreatment (CM). CM patients exhibited a significantly reduced olfactory threshold and identification ability. The OB volume of the CM patients was significantly reduced to 80% of the non-CM patients. In conclusion, postnatal neurogenesis might be by reduced in CM, which may affect olfactory function of the brain in later life. Alternatively, a reduced OB volume may enhance psychological vulnerability in the presence of adverse childhood conditions although other areas not analyzed in this study may also be involved. PMID:24051351

  12. Olfactory Dysfunction in Older Adults is Associated with Feelings of Depression and Loneliness.

    PubMed

    Sivam, Anita; Wroblewski, Kristen E; Alkorta-Aranburu, Gorka; Barnes, Lisa L; Wilson, Robert S; Bennett, David A; Pinto, Jayant M

    2016-05-01

    Olfactory dysfunction is a common complaint among physician visits. Olfactory loss affects quality of life and impairs function and activities of daily living. The purpose of our study was to assess the degree of odor identification associated with mental health. Olfactory function was measured using the brief smell identification test. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression scale. Loneliness was assessed by the de Jong-Gierveld Loneliness Scale. Cognition was measured by a battery of 19 cognitive tests. The frequency of olfactory dysfunction in our study was ~40%. Older subjects had worse olfactory performance, as previously found. More loneliness was associated with worse odor identification. Similarly, symptoms of depression were associated with worse olfaction (among men). Although better global cognitive function was strongly associated with better odor identification, after controlling for multiple factors, the associations with depression and loneliness were unchanged. Clinicians should assess these mental health conditions when treating older patients who present with olfactory deficits. PMID:26809485

  13. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  14. Development of the olfactory and vomeronasal organs in Discoglossus pictus (Discoglossidae, Anura).

    PubMed

    Královec, Karel; Žáková, Pavla; Mužáková, Vladimíra

    2013-01-01

    Using histological techniques and computer-aided three-dimensional reconstructions of histological serial sections, we studied the development of the olfactory and vomeronasal organs in the discoglossid frog Discoglossus pictus. The olfactory epithelium in larval D. pictus represents one continuous unit of tissue not divided into two separate portions. However, a small pouch of olfactory epithelium (the "ventromedial diverticulum") is embedded into the roof of the buccal cavity, anteromedial to the internal naris. The lateral appendix is present in D. pictus through the entire larval period and disappears during the onset of metamorphosis. The disappearance of the lateral appendix at this time suggests that it is a typical larval organ related to aquatic life. The vomeronasal organ develops during hindlimb development, which is comparatively late for anurans. The development of the vomeronasal organ in D. pictus follows the same general developmental pattern recognized for neobatrachians. As with most anurans, the vomeronasal glands appear later than the vomeronasal organ. After metamorphosis, the olfactory organ of adult D. pictus is composed of a series of three interconnected chambers: the cavum principale, cavum medium, and cavum inferius. We suggest that the ventromedial diverticulum at the anterior border of the internal naris of larval D. pictus might be homologous with the ventral olfactory epithelium of bufonids and with the similar diverticulum of Alytes. PMID:22972712

  15. Notch Is Required in Adult Drosophila Sensory Neurons for Morphological and Functional Plasticity of the Olfactory Circuit

    PubMed Central

    Struhl, Gary

    2015-01-01

    Olfactory receptor neurons (ORNs) convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs). We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl) in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse. PMID:26011623

  16. Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.

    PubMed

    García-González, Diego; Murcia-Belmonte, Verónica; Esteban, Pedro F; Ortega, Felipe; Díaz, David; Sánchez-Vera, Irene; Lebrón-Galán, Rafael; Escobar-Castañondo, Laura; Martínez-Millán, Luis; Weruaga, Eduardo; García-Verdugo, José Manuel; Berninger, Benedikt; de Castro, Fernando

    2016-01-01

    New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB. PMID:25300351

  17. Deep sequencing of the murine olfactory receptor neuron transcriptome.

    PubMed

    Kanageswaran, Ninthujah; Demond, Marilen; Nagel, Maximilian; Schreiner, Benjamin S P; Baumgart, Sabrina; Scholz, Paul; Altmüller, Janine; Becker, Christian; Doerner, Julia F; Conrad, Heike; Oberland, Sonja; Wetzel, Christian H; Neuhaus, Eva M; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The ability of animals to sense and differentiate among thousands of odorants relies on a large set of olfactory receptors (OR) and a multitude of accessory proteins within the olfactory epithelium (OE). ORs and related signaling mechanisms have been the subject of intensive studies over the past years, but our knowledge regarding olfactory processing remains limited. The recent development of next generation sequencing (NGS) techniques encouraged us to assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and male adult mice and from fluorescence-activated cell sorting (FACS)-sorted olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per transcriptome. In OE samples, nearly all OR and trace amine-associated receptor (TAAR) genes involved in the perception of volatile amines were detectably expressed. Other genes known to participate in olfactory signaling pathways were among the 200 genes with the highest expression levels in the OE. To identify OE-specific genes, we compared olfactory neuron expression profiles with RNA-Seq transcriptome data from different murine tissues. By analyzing different transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and established an expression ranking for GPCRs detected in the OE. We also identified other previously undescribed membrane proteins as potential new players in olfaction. The quantitative and comprehensive transcriptome data provide a virtually complete catalogue of genes expressed in the OE and present a useful tool to uncover candidate genes involved in, for example, olfactory signaling, OR trafficking and recycling, and proliferation. PMID:25590618

  18. Neural crest and placode contributions to olfactory development.

    PubMed

    Suzuki, Jun; Osumi, Noriko

    2015-01-01

    Olfaction is the sense of smell that influences many primitive behaviors for survival, e.g., feeding, reproduction, social interaction, and fear response. The olfactory system is an evolutionarily ancient sensory system and composed of the olfactory epithelium (OE), the olfactory bulb (OB), and the olfactory cortex. The OE gives rise to olfactory receptor neurons (ORNs), i.e., primary sensory receptor cells whose axons project directly to the OB. The ORNs are unique in the way that they are continuously replaced during physiological turnover or following injury throughout life. In the OE, horizontal basal cells, i.e., flat and quiescent cells attached to the basal lamina, are now thought to be tissue stem cells. Although OE cells, especially ORNs, were hypothesized to be derived from the olfactory placode (OP), recent genetic fate-mapping studies using Cre reporter mice indicate a dual origin, i.e., the OP and neural crest (NC), of the olfactory system. The NC is a transient embryonic tissue that is formed between the dorsal neuroepithelium and epidermis. Neural crest cells (NCCs) are multipotent cells that migrate into various target tissues and differentiate into various cell types, including neurons and glia of the peripheral nervous system, cranial cartilage and bone, and melanocytes. Recent studies have revealed that neural crest-derived cells (NCDCs) are widely distributed in adult tissues, and that a subset of NCDCs still possesses NCC-like multipotency. Here, we review classical and recent studies of the olfactory system, especially focusing on the contribution of the NC and OP to the OE development. PMID:25662265

  19. Deep Sequencing of the Murine Olfactory Receptor Neuron Transcriptome

    PubMed Central

    Kanageswaran, Ninthujah; Demond, Marilen; Nagel, Maximilian; Schreiner, Benjamin S. P.; Baumgart, Sabrina; Scholz, Paul; Altmüller, Janine; Becker, Christian; Doerner, Julia F.; Conrad, Heike; Oberland, Sonja; Wetzel, Christian H.; Neuhaus, Eva M.; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The ability of animals to sense and differentiate among thousands of odorants relies on a large set of olfactory receptors (OR) and a multitude of accessory proteins within the olfactory epithelium (OE). ORs and related signaling mechanisms have been the subject of intensive studies over the past years, but our knowledge regarding olfactory processing remains limited. The recent development of next generation sequencing (NGS) techniques encouraged us to assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and male adult mice and from fluorescence-activated cell sorting (FACS)-sorted olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per transcriptome. In OE samples, nearly all OR and trace amine-associated receptor (TAAR) genes involved in the perception of volatile amines were detectably expressed. Other genes known to participate in olfactory signaling pathways were among the 200 genes with the highest expression levels in the OE. To identify OE-specific genes, we compared olfactory neuron expression profiles with RNA-Seq transcriptome data from different murine tissues. By analyzing different transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and established an expression ranking for GPCRs detected in the OE. We also identified other previously undescribed membrane proteins as potential new players in olfaction. The quantitative and comprehensive transcriptome data provide a virtually complete catalogue of genes expressed in the OE and present a useful tool to uncover candidate genes involved in, for example, olfactory signaling, OR trafficking and recycling, and proliferation. PMID:25590618

  20. Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb.

    PubMed

    Wu, Jyun-Han; Han, Yueh-Ting; Yu, Jenn-Yah; Wang, Tsu-Wei

    2013-08-01

    Pheromones from urine of unfamiliar conspecific male animals can reinitiate a female's estrus cycle to cause pregnancy block through the vomeronasal organ (VNO)-accessory olfactory bulb (AOB)-hypothalamic pathway. This phenomenon is called the Bruce effect. Pheromones from the mate of the female, however, do not trigger re-entrance of the estrus cycle because an olfactory memory toward its mate is formed. The activity of the VNO-AOB-hypothalamic pathway is negatively modulated by GABAergic granule cells in the AOB. Since these cells are constantly replenished by neural stem cells in the subventricular zone (SVZ) of the lateral ventricle throughout adulthood and adult neurogenesis is required for mate recognition and fertility, we tested the hypothesis that pheromones from familiar and unfamiliar males may have different effects on adult AOB neurogenesis in female mice. When female mice were exposed to bedding used by a male or lived with one, cell proliferation and neuroblast production in the SVZ were increased. Furthermore, survival of newly generated cells in the AOB was enhanced. This survival effect was transient and mediated by norepinephrine. Interestingly, male bedding-induced newborn cell survival in the AOB but not cell proliferation in the SVZ was attenuated when females were subjected to bedding from an unfamiliar male. Our results indicate that male pheromones from familiar and unfamiliar males exert different effects on neurogenesis in the adult female AOB. Given that adult neurogenesis is required for reproductive behaviors, these divergent pheromonal effects may provide a mechanism for the Bruce effect. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 632-645, 2013. PMID:23696538

  1. Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors.

    PubMed

    Ohigashi, Izumi; Zuklys, Saulius; Sakata, Mie; Mayer, Carlos E; Hamazaki, Yoko; Minato, Nagahiro; Hollander, Georg A; Takahama, Yousuke

    2015-11-17

    Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny. PMID:26549457

  2. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat

    PubMed Central

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A.

    2016-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID:26858596

  3. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat.

    PubMed

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A

    2015-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID:26858596

  4. Analysis of glycoproteins produced by the associated gland in the olfactory organ of lungfish.

    PubMed

    Nakamuta, Nobuaki; Nakamuta, Shoko; Taniguchi, Kazumi; Taniguchi, Kazuyuki

    2013-07-31

    The olfactory organ of African lungfish, Protopterus annectens, contains two distinct sensory epithelia: the lamellar olfactory epithelium and the recess epithelium. These epithelia correspond to the olfactory epithelium and the vomeronasal organ of tetrapods, respectively. In contrast to the lamellar olfactory epithelium, which has no associated gland, the recess epithelium is equipped with associated glands. Although the glandular cells and/or the supporting cells are generally presumed to secrete proteins involved in the function of olfactory sensory epithelia, the properties of these proteins in lungfish have not been evaluated to date. In this study, we investigated the associated glands in the olfactory organ of lungfish by transmission electron microscopy and found that the glandular cells contain numerous secretory granules and secrete them from the apical membrane. In addition, we analyzed the olfactory organ by lectin histochemistry using 16 biotinylated lectins. All lectins labeled the secretory granules in the glandular cells with different staining patterns from those of the supporting cells in the lamellar olfactory epithelium or in the recess epithelium. Furthermore, lectin blotting analysis showed that multiple bands were detected by the lectins which specifically labeled the glandular epithelium of the olfactory organ. These results indicate that the secretory products of the associated glands in the recess epithelium have different properties from those of the supporting cells in the olfactory sensory epithelia and contain multiple glycoproteins with different carbohydrate moieties. PMID:23428778

  5. Dog and mouse: toward a balanced view of the mammalian olfactory system.

    PubMed

    Barrios, Arthur W; Sánchez-Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    Although the most intensively studied mammalian olfactory system is that of the mouse, in which olfactory chemical cues of one kind or another are detected in four different nasal areas [the main olfactory epithelium (MOE), the septal organ (SO), Grüneberg's ganglion, and the sensory epithelium of the vomeronasal organ (VNO)], the extraordinarily sensitive olfactory system of the dog is also an important model that is increasingly used, for example in genomic studies of species evolution. Here we describe the topography and extent of the main olfactory and vomeronasal sensory epithelia of the dog, and we report finding no structures equivalent to the Grüneberg ganglion and SO of the mouse. Since we examined adults, newborns, and fetuses we conclude that these latter structures are absent in dogs, possibly as the result of regression or involution. The absence of a vomeronasal component based on VR2 receptors suggests that the VNO may be undergoing a similar involutionary process. PMID:25309347

  6. Aberrant Adult Neurogenesis in the Subventricular Zone-Rostral Migratory Stream-Olfactory Bulb System Following Subchronic Manganese Exposure.

    PubMed

    Fu, Sherleen; Jiang, Wendy; Gao, Xiang; Zeng, Andrew; Cholger, Daniel; Cannon, Jason; Chen, Jinhui; Zheng, Wei

    2016-04-01

    Adult neurogenesis occurs in brain subventricular zone (SVZ). Our recent data reveal an elevated proliferation of BrdU(+) cells in SVZ following subchronic manganese (Mn) exposure in rats. This study was designed to distinguish Mn effect on the critical stage of adult neurogenesis, ie, proliferation, migration, survival and differentiation from the SVZ via the rostral migratory stream to the olfactory bulb (OB). Adult rats received a single ip-dose of BrdU at the end of 4-week Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (P< .05). These BrdU(+) cells were identified as a mixed population of mainly GFAP(+) type-B neural stem cells, Nestin(+) type-C transit progenitor cells, DCX(+) migratory neuroblasts and Iba1(+) microglial cells. Another group of adult rats received 3 daily ip-injections of BrdU followed by subchronic Mn exposure. By 4-week post BrdU labeling, most of the surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in OB were 33% and 64% in Mn-exposed and control animals, respectively (P< .01). Infusion of Cu directly into the lateral ventricle significantly decreased the cell proliferation in the SVZ. Taken together, these results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB. PMID:26794142

  7. Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein.

    PubMed

    Marxreiter, Franz; Nuber, Silke; Kandasamy, Mahesh; Klucken, Jochen; Aigner, Robert; Burgmayer, Ralf; Couillard-Despres, Sebastien; Riess, Olaf; Winkler, Jürgen; Winner, Beate

    2009-03-01

    In familial and sporadic forms of Parkinson's disease (PD), alpha-synuclein pathology is present in the brain stem nuclei and olfactory bulb (OB) long before Lewy bodies are detected in the substantia nigra. The OB is an active region of adult neurogenesis, where newly generated neurons physiologically integrate. While accumulation of wild-type alpha-synuclein is one of the pathogenic hallmarks of non-genetic forms of PD, the A30P alpha-synuclein mutation results in an earlier disease onset and a severe clinical phenotype. Here, we study the regulation of adult neurogenesis in the subventricular zone (SVZ)/OB system in a tetracycline-suppressive (tet-off) transgenic model of synucleinopathies, expressing human mutant A30P alpha-synuclein under the control of the calcium/calmodulin-dependent protein kinase II alpha (CaMK) promoter. In A30P transgenic mice alpha-synuclein was abundant at the site of integration in the glomerular cell layer of the OB. Without changes in proliferation in the SVZ, significantly fewer newly generated neurons were observed in the OB granule cell and glomerular layers of A30P transgenic mice than in controls, most probably due to increased cell death. By tetracycline-dependent abrogation of A30P alpha-synuclein expression, OB neurogenesis and programmed cell death was restored to control levels. Our results indicate that, using A30P conditional (tet-off) mice, A30P alpha-synuclein has a negative impact on olfactory neurogenesis and suppression of A30P alpha-synuclein enhances survival of newly generated neurons. This finding suggests that interfering with alpha-synuclein pathology can rescue newly generated neurons, possibly leading to new targets for therapeutic interventions in synucleinopathies. PMID:19291219

  8. Functional and Molecular Characterization of Rod-like Cells from Retinal Stem Cells Derived from the Adult Ciliary Epithelium

    PubMed Central

    Demontis, Gian Carlo; Aruta, Claudia; Comitato, Antonella; De Marzo, Anna; Marigo, Valeria

    2012-01-01

    In vitro generation of photoreceptors from stem cells is of great interest for the development of regenerative medicine approaches for patients affected by retinal degeneration and for high throughput drug screens for these diseases. In this study, we show unprecedented high percentages of rod-fated cells from retinal stem cells of the adult ciliary epithelium. Molecular characterization of rod-like cells demonstrates that they lose ciliary epithelial characteristics but acquire photoreceptor features. Rod maturation was evaluated at two levels: gene expression and electrophysiological functionality. Here we present a strong correlation between phototransduction protein expression and functionality of the cells in vitro. We demonstrate that in vitro generated rod-like cells express cGMP-gated channels that are gated by endogenous cGMP. We also identified voltage-gated channels necessary for rod maturation and viability. This level of analysis for the first time provides evidence that adult retinal stem cells can generate highly homogeneous rod-fated cells. PMID:22432014

  9. Expression of Two Classes of Pax6 Transcripts in Reprogramming Retinal Pigment Epithelium Cells of the Adult Newt.

    PubMed

    Inami, Wataru; Islam, Md Rafiqul; Nakamura, Kenta; Yoshikawa, Taro; Yasumuro, Hirofumi; Casco-Robles, Martin Miguel; Toyama, Fubito; Maruo, Fumiaki; Chiba, Chikafumi

    2016-02-01

    The adult newt has the remarkable ability to regenerate a functional retina from retinal pigment epithelium (RPE) cells, even when the neural retina (NR) is completely lost from the eye. In this system, RPE cells are reprogrammed into a unique state of multipotent cells, named RPESCs, in an early phase of retinal regeneration. However, the signals that trigger reprogramming remain unknown. Here, to approach this issue we focused on Pax6, a transcription factor known to be expressed in RPESCs. We first identified four classes (v1, v2, v3 and v4) of Pax6 variants in the eye of adult newt, Cynops pyrrhogaster. These variants were expressed in most tissues of the intact eye in different combinations but not in the RPE, choroid or sclera. On the basis of this information, we investigated the expression of Pax6 in RPE cells after the NR was removed from the eye by surgery (retinectomy), and found that two classes (v1 and v2) of Pax6 variants were newly expressed in RPE cells 10 days after retinectomy, both in vivo and in vitro (RLEC system). In the RLEC system, we found that Pax6 expression is mediated through a pathway separate from the MEK-ERK pathway, which is required for cell cycle re-entry of RPE cells. These results predict the existence of a pathway that may be of fundamental importance to a better understanding of the reprogramming of RPE cells in vivo. PMID:26853865

  10. Olfactory neuroepithelium transplanted onto the parietal cortex of rats: electroolfactogram in absence of connections with the host brain.

    PubMed

    Amemori, T; Soukup, T; Bures

    1987-05-01

    A technique, allowing continuous electrophysiological monitoring of the functional properties of transplanted olfactory neuroepithelium is described. Viability of isolated parts of nasal mucosa obtained from adult rats was tested in vitro. Pieces of olfactory neuroepithelium (2 X 2 mm) were transplanted onto the exposed parietal cortex of adult rats and protected by plastic wells covered with a transparent lid. At one-week intervals the lid was removed and the transplanted epithelium was tested for electrical responses to amyl acetate vapours. Reliable electroolfactograms appeared 3 weeks after transplantation and could be elicited in 60% of transplants (n = 15) during the subsequent 6 weeks but disappeared later. Morphological control at the conclusion of the experiment showed that the transplant consisted of pieces of epithelium forming vesicular or semivesicular structures but not containing olfactory sensory neurons and not connected with the host brain. It is concluded that the method allows recording responses of the transplanted neuroepithelium to olfactory stimuli but does not yield a sufficiently stable preparation for establishing ectopic olfactory input to the brain. PMID:3610502

  11. Gap junctions in olfactory neurons modulate olfactory sensitivity

    PubMed Central

    2010-01-01

    Background One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis. Results I generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited c-fos mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons. Conclusions My study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory

  12. Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

    PubMed Central

    2012-01-01

    Background The primary olfactory pathway is a potential route through which microorganisms from the periphery could potentially access the central nervous system. Our previous studies demonstrated that if the olfactory epithelium was damaged, bacteria administered into the nasal cavity induced nitric oxide production in olfactory ensheathing cells. This study investigates the cytokine profile of olfactory tissues as a consequence of bacterial challenge and establishes whether or not the bacteria are able to reach the olfactory bulb in the central nervous system. Methods The olfactory epithelium of C57BL/6 mice was damaged by unilateral Triton X-100 nasal washing, and Staphylococcus aureus was administered ipsilaterally 4 days later. Olfactory mucosa and bulb were harvested 6 h, 24 h and 5 days after inoculation and their cytokine profile compared to control tissues. The fate of S. aureus and the response of bulbar microglia were examined using fluorescence microscopy and transmission electron microscopy. Results In the olfactory mucosa, administered S. aureus was present in supporting cells of the olfactory epithelium, and macrophages and olfactory nerve bundles in the lamina propria. Fluorescein isothiocyanate-conjugated S. aureus was observed within the olfactory mucosa and bulb 6 h after inoculation, but remained restricted to the peripheral layers up to 5 days later. At the 24-h time point, the level of interleukin-6 (IL-6) and tumour necrosis factor-α in the compromised olfactory tissues challenged with bacteria (12,466 ± 956 pg/ml and 552 ± 193 pg/ml, respectively) was significantly higher than that in compromised olfactory tissues alone (6,092 ± 1,403 pg/ml and 80 ± 2 pg/ml, respectively). Immunohistochemistry confirmed that IL-6 was present in several cell types including olfactory ensheathing cells and mitral cells of the olfactory bulb. Concurrently, there was a 4.4-, 4.5- and 2.8-fold increase in the density of i

  13. Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.

    PubMed

    Moore, Benjamin D; Khurana, Shradha S; Huh, Won Jae; Mills, Jason C

    2016-08-01

    We have previously shown that the sequential transcription factors Xbp1→Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4α(flox/flox) adult mouse stomachs after tamoxifen-induced deletion of Hnf4α We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α) and Xbp1 in mouse stomach and human gastric cells. We show that HNF4α protein is expressed in pit (foveolar) cells, mucous neck cells, and zymogenic chief cells (ZCs) of the corpus gastric unit. Loss of HNF4α in adult mouse stomach led to reduced ZC size and ER content, phenocopying previously characterized effects of Xbp1 deletion. However, HNF4α(Δ/Δ) stomachs also exhibited additional phenotypes including increased proliferation in the isthmal stem cell zone and altered mucous neck cell migration, indicating a role of HNF4α in progenitor cells as well as in ZCs. HNF4α directly occupies the Xbp1 promoter locus in mouse stomach, and forced HNF4α expression increased abundance of XBP1 mRNA in human gastric cancer cells. Finally, as expected, loss of HNF4α caused decreased Xbp1 and Mist1 expression in mouse stomachs. We show that HNF4α regulates homeostatic proliferation in the gastric epithelium and is both necessary and sufficient for the upstream regulation of the Xbp1→Mist1 axis in maintenance of ZC secretory architecture. PMID:27340127

  14. Either main or accessory olfactory system signaling can mediate the rewarding effects of estrous female chemosignals in sexually naive male mice.

    PubMed

    Korzan, Wayne J; Freamat, Mihael; Johnson, Adam G; Cherry, James A; Baum, Michael J

    2013-10-01

    A long-held view has been that interest of male mice in female body odors reflects an activation of reward circuits in the male brain following their detection by the vomeronasal organ (VNO) and processing via the accessory olfactory system. We found that adult, sexually naive male mice acquired a conditioned place preference (CPP) after repeatedly receiving estrous female urine on the nose and being placed in an initially nonpreferred chamber with soiled estrous bedding on the floor. CPP was not acquired in control mice that received saline on the nose before being placed in a nonpreferred chamber with clean bedding. Robust acquisition of a CPP using estrous female odors as the reward persisted in separate groups of mice in which VNO-accessory olfactory function was disrupted by bilateral lesioning of the accessory olfactory bulb (AOB) or in which main olfactory function was disrupted by zinc sulfate lesions of the main olfactory epithelium (MOE). By contrast, no CPP was acquired for estrous odors in males that received combined AOB and MOE lesions. Either the main or the accessory olfactory system suffices to mediate the rewarding effects of estrous female odors in the male mouse, even in the absence of prior mating experience. The main olfactory system is part of the circuitry that responds to chemosignals involved in motivated behavior, a role that may be particularly important for humans who lack a functional accessory olfactory system. PMID:23978150

  15. Tumorigenic Potential of Olfactory Bulb-Derived Human Adult Neural Stem Cells Associates with Activation of TERT and NOTCH1

    PubMed Central

    Ricci-Vitiani, Lucia; Cenciarelli, Carlo; Petrucci, Giovanna; Milazzo, Luisa; Montano, Nicola; Tabolacci, Elisabetta; Maira, Giulio; Larocca, Luigi M.; Pallini, Roberto

    2009-01-01

    Background Multipotent neural stem cells (NSCs) have been isolated from neurogenic regions of the adult brain. Reportedly, these cells can be expanded in vitro under prolonged mitogen stimulation without propensity to transform. However, the constitutive activation of the cellular machinery required to bypass apoptosis and senescence places these cells at risk for malignant transformation. Methodology/Principal Findings Using serum-free medium supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), we established clonally derived NS/progenitor cell (NS/PC) cultures from the olfactory bulb (OB) of five adult patients. The NS/PC cultures obtained from one OB specimen lost growth factor dependence and neuronal differentiation at early passage. These cells developed glioblastoma tumors upon xenografting in immunosuppressed mice. The remaining NS/PC cultures were propagated either as floating neurospheres or as adherent monolayers with mainteinance of growth factor dependence and multipotentiality at late passage. These cells were engrafted onto the CNS of immunosuppressed rodents. Overall, the grafted NS/PCs homed in the host parenchyma showing ramified morphology and neuronal marker expression. However, a group of animals transplanted with NS/PCs obtained from an adherent culture developed fast growing tumors histologically resembling neuroesthesioblastoma. Cytogenetic and molecular analyses showed that the NS/PC undergo chromosomal changes with repeated in vitro passages under mitogen stimulation, and that up-regulation of hTERT and NOTCH1 associates with in vivo tumorigenicity. Conclusions/Significance Using culturing techniques described in current literature, NS/PCs arise from the OB of adult patients which in vivo either integrate in the CNS parenchyma showing neuron-like features or initiate tumor formation. Extensive xenografting studies on each human derived NS cell line appear mandatory before any use of these cells in the

  16. The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis.

    PubMed

    Lim, Daniel A; Alvarez-Buylla, Arturo

    2016-01-01

    A large population of neural stem/precursor cells (NSCs) persists in the ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell-intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors. PMID:27048191

  17. p63 regulates olfactory stem cell self-renewal and differentiation

    PubMed Central

    Fletcher, Russell B.; Prasol, Melanie S.; Estrada, Jose; Baudhuin, Ariane; Vranizan, Karen; Choi, Yoon-Gi; Ngai, John

    2011-01-01

    Summary The olfactory epithelium is a sensory neuroepithelium that supports adult neurogenesis and tissue regeneration following injury, making it an excellent model for investigating neural stem cell regulation in vivo. Previous studies have identified the horizontal basal cell (HBC) as the neural stem cell of the postnatal olfactory epithelium. The molecules and pathways regulating HBC self-renewal and differentiation are unknown, however. In the present study we demonstrate that the transcription factor p63, a member of the p53 tumor suppressor gene family known to regulate stem cell dynamics in other epithelia, is highly enriched in HBCs. We show that p63 is required cell-autonomously for olfactory stem cell renewal and further demonstrate that p63 functions to repress HBC differentiation. These results provide critical insight into the genetic regulation of the olfactory stem cell in vivo, and more generally provide an entrée toward understanding the coordination of stem cell self-renewal and differentiation. PMID:22153372

  18. Goα expression in the vomeronasal organ and olfactory bulb of the tammar wallaby.

    PubMed

    Schneider, Nanette Y; Fletcher, Terrence P; Shaw, Geoff; Renfree, Marilyn B

    2012-07-01

    The vomeronasal organ (VNO) detects pheromones via 2 large families of receptors: vomeronasal receptor 1, associated with the protein Giα2, and vomeronasal receptor 2, associated with Goα. We investigated the distribution of Goα in the developing and adult VNO and adult olfactory bulb of a marsupial, the tammar wallaby. Some cells expressed Goα as early as day 5 postpartum, but by day 30, Goα expressing cells were distributed throughout the receptor epithelium of the VNO. In the adult tammar, Goα appeared to be expressed in sensory neurons whose nuclei were mostly basally located in the vomeronasal receptor epithelium. Goα expressing vomeronasal receptor cells led to all areas of the accessory olfactory bulb (AOB). The lack of regionally restricted projection of the vomeronasal receptor cell type 2 in the tammar was similar to the uniform type, with the crucial difference that the uniform type only shows expression of Giα2 and no expression of Goα. The observed Goα staining pattern suggests that the tammar may have a third accessory olfactory type that could be intermediate to the segregated and uniform types already described. PMID:22383629

  19. Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in mice.

    PubMed

    Barrios, Arthur W; Núñez, Gonzalo; Sánchez Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    The four regions of the murine nasal cavity featuring olfactory neurons were studied anatomically and by labeling with lectins and relevant antibodies with a view to establishing criteria for the identification of olfactory subsystems that are readily applicable to other mammals. In the main olfactory epithelium and the septal organ the olfactory sensory neurons (OSNs) are embedded in quasi-stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium lining the medial interior wall of the vomeronasal duct and do not make contact with the mucosa of the main nasal cavity; and in Grüneberg's ganglion a small isolated population of OSNs lies adjacent to, but not within, the epithelium. With the exception of Grüneberg's ganglion, all the tissues expressing olfactory marker protein (OMP) (the above four nasal territories, the vomeronasal and main olfactory nerves, and the main and accessory olfactory bulbs) are also labeled by Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all and only tissues expressing Gαi2 (the apical sensory neurons of the vomeronasal organ, their axons, and their glomerular destinations in the anterior accessory olfactory bulb). These staining patterns of UEA-I and LEA may facilitate the characterization of olfactory anatomy in other species. A 710-section atlas of the anatomy of the murine nasal cavity has been made available on line. PMID:25071468

  20. Profiling of olfactory receptor gene expression in whole human olfactory mucosa.

    PubMed

    Verbeurgt, Christophe; Wilkin, Françoise; Tarabichi, Maxime; Gregoire, Françoise; Dumont, Jacques E; Chatelain, Pierre

    2014-01-01

    Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the

  1. Profiling of Olfactory Receptor Gene Expression in Whole Human Olfactory Mucosa

    PubMed Central

    Tarabichi, Maxime; Gregoire, Françoise; Dumont, Jacques E.; Chatelain, Pierre

    2014-01-01

    Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the

  2. Gene Expression Profile of Adult Human Olfactory Bulb and Embryonic Neural Stem Cell Suggests Distinct Signaling Pathways and Epigenetic Control

    PubMed Central

    Marei, Hany E. S.; Ahmed, Abd-Elmaksoud; Michetti, Fabrizio; Pescatori, Mario; Pallini, Roberto; Casalbore, Patricia; Cenciarelli, Carlo; Elhadidy, Mohamed

    2012-01-01

    Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults. PMID:22485144

  3. Distribution and function of splash, an achaete-scute homolog in the adult olfactory organ of the Caribbean spiny lobster Panulirus argus.

    PubMed

    Tadesse, Tizeta; Schmidt, Manfred; Walthall, William W; Tai, Phang C; Derby, Charles D

    2011-04-01

    achaete-scute complex (ASC) genes, which encode basic helix-loop-helix transcription factors, regulate embryonic and adult neurogenesis in many animals. In adult arthropods, including crustaceans, ASC homologs have been identified but rarely functionally characterized. We took advantage of the recently identified crustacean homolog, splash (spiny lobster achaete scute homolog), in the olfactory organ of the Caribbean spiny lobster Panulirus argus to examine its role in adult neurogenesis. We tested the hypothesis that splash is associated with but not restricted to sensory neuron formation in the olfactory organ, the antennular lateral flagellum (LF), of adult spiny lobsters. We demonstrated splash labeling in epithelial cells across LF developmental zones (i.e., proliferation and mature zones), in auxiliary cells surrounding dendrites of olfactory receptor neurons (ORNs), and in immature and mature ORNs, but not in granulocytes or chromatophores. Since ORN proliferation varies with molt stage, we examined splash expression across molt stages and found that molt stage affected splash expression in the ORN mature zone but not in the proliferation zone. In vivo incorporation of bromodeoxyuridine (BrdU) showed no correlation in the cellular pattern of splash expression and BrdU labeling. The intensity of splash labeling was dramatically enhanced in the proliferation zones following LF damage, suggesting enhanced splash expression during repair and/or regeneration. We conclude that splash is not closely associated with the formation of sensory neurons under normal physiological conditions, and we propose that splash is involved in repair and regeneration. We also propose that splash has additional roles other than neurogenesis in adult crustaceans. PMID:21394934

  4. Spatiotemporal Alterations in Primary Odorant Representations in Olfactory Marker Protein Knockout Mice

    PubMed Central

    Kass, Marley D.; Moberly, Andrew H.; McGann, John P.

    2013-01-01

    Olfactory marker protein (OMP) is highly and selectively expressed in primary olfactory sensory neurons (OSNs) across species, but its physiological function remains unclear. Previous studies in the olfactory epithelium suggest that it accelerates the neural response to odorants and may modulate the odorant-selectivity of OSNs. Here we used a line of gene-targeted mice that express the fluorescent exocytosis indicator synaptopHluorin in place of OMP to compare spatiotemporal patterns of odorant-evoked neurotransmitter release from OSNs in adult mice that were heterozygous for OMP or OMP-null. We found that these patterns, which constitute the primary neural representation of each odorant, developed more slowly during the odorant presentation in OMP knockout mice but eventually reached the same magnitude as in heterozygous mice. In the olfactory bulb, each glomerulus receives synaptic input from a subpopulation of OSNs that all express the same odor receptor and thus typically respond to a specific subset of odorants. We observed that in OMP knockout mice, OSNs innervating a given glomerulus typically responded to a broader range of odorants than in OMP heterozygous mice and thus each odorant evoked synaptic input to a larger number of glomeruli. In an olfactory habituation task, OMP knockout mice behaved differently than wild-type mice, exhibiting a delay in their onset to investigate an odor stimulus during its first presentation and less habituation to that stimulus over repeated presentations. These results suggest that the actions of OMP in olfactory transduction carry through to the primary sensory representations of olfactory stimuli in adult mice in vivo. PMID:23630588

  5. Follistatin-like 5 is expressed in restricted areas of the adult mouse brain: Implications for its function in the olfactory system.

    PubMed

    Masuda, Tomoyuki; Sakuma, Chie; Nagaoka, Atsuko; Yamagishi, Toshiyuki; Ueda, Shuichi; Nagase, Takahiro; Yaginuma, Hiroyuki

    2014-02-01

    Follistatin-like 5 (Fstl5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous studies revealed that other members of this family including Fstl1 and Fstl3 play an essential role in development, homeostasis, and congenital disorders. However, the in vivo function of Fstl5 is poorly understood. To gain insight into the function of Fstl5 in the mouse central nervous system, we examined the Fstl5 expression pattern in the adult mouse brain. The results of in situ hybridization analysis showed a highly restricted pattern of Fstl5, namely, with localization in the olfactory system, hippocampal CA3 area and granular cell layer of the cerebellum. Restricted expression in the olfactory system suggests a possible role for Fstl5 in maintaining odor perception. PMID:24588779

  6. Cross-adaptation to odor stimulation of olfactory receptor cells in the box turtle, Terrapene carolina.

    PubMed

    Tonosaki, K

    1993-01-01

    Electrical recording from small twigs of olfactory nerve and electro-olfactogram (EOG) from olfactory epithelium in a turtle shows that olfactory receptors in the nose are responsive to various odors. I have used the effects of cross-adaptation to odor stimulation on the olfactory receptors to investigate the stimulus-specific components of these responses and to provide information about the responsiveness of cells. The results of the cross-adaptation experiments strongly support the hypothesis that different categories of receptor cells exist in the olfactory epithelium. PMID:8386588

  7. Adult depression-like behavior, amygdala and olfactory cortex functions are restored by odor previously paired with shock during infant's sensitive period attachment learning

    PubMed Central

    Sevelinges, Yannick; Mouly, Anne-Marie; Raineki, Charlis; Moriceau, Stéphanie; Forest, Christina; Sullivan, Regina M.

    2010-01-01

    Maltreatment from the caregiver induces vulnerability to later life psychopathologies, yet attraction and comfort is sometimes provided by cues associated with early life maltreatment. We used a rat model of early life maltreatment with odor-0.5mA shock conditioning to produce depressive-like behaviors and questioned whether stimuli associated with maltreatment would restore emotional neurobehavioral function to control levels. Pups received daily novel odor-0.5mA shock conditioning from postnatal day 8 to 12. This procedure produces a new maternal odor that controls pups' attachment behaviors. In adulthood, either with or without the infant odor, animals received a Forced Swim Test, Sucrose Preference Test or assessment of amygdala and olfactory system functioning using field potential signal evoked by olfactory bulb paired-pulse electrical stimulation. Following neonatal odor-shock pairings, but not unpaired controls, adults without the odor present showed increased depression-like behavior in the Forced Swim Test and Sucrose Preference Test and a deficit in paired-pulse inhibition in amygdala and piriform (olfactory) cortex. All effects were brought to control levels when the infant conditioned odor was presented during behavioral and neural tests. The ability of cues associated with early life maltreatment to normalize behavior and amygdala activity suggests these cues provide adaptive value in adulthood. PMID:21037982

  8. Paraneoplastic syndromes in olfactory neuroblastoma

    PubMed Central

    Gabrych, Anna; Czapiewski, Piotr; Sworczak, Krzysztof

    2015-01-01

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature. PMID:26199564

  9. FUNCTIONAL DEFICITS PRODUCED BY 3-METHYLINDOLE-INDUCED OLFACTORY MUCOSAL DAMAGE REVEALED BY A SIMPLE OLFACTORY LEARNING TASK

    EPA Science Inventory

    Methods for assessing functional consequences of olfactory mucosal damage were examined in rats exposed to 3-methylindole (3-MI). Treatment with 3-MI (400 mg/kg) induced severe degeneration of olfactory sensory epithelium followed by regeneration, fibrous adhesions and osseous re...

  10. Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence☆

    PubMed Central

    Dorà, Natalie J.; Hill, Robert E.; Collinson, J. Martin; West, John D.

    2015-01-01

    The limbal epithelial stem cell (LESC) hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC) hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks. PMID:26554513

  11. Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model

    PubMed Central

    Jung, Yong Gi; Lane, Andrew P.

    2016-01-01

    Objective To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (Etanercept) on an inducible olfactory inflammation (IOI) mouse model Study Design An in vivo study using a transgenic mouse model Setting Research laboratory Subjects and Methods To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis (CRS)-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally-controlled fashion specifically within the olfactory epithelium. In one group of mice (n=4), Etanercept was injected intraperitoneally (100 µg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n=2) underwent induction of TNF-α expression for 8 weeks, with Etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with equal number of control group. Results Compared to non-treated IOI mice, Etanercept -treated IOI mice showed significantly improved EOG responses after 2 weeks (p<0.001). After 8 weeks of induced inflammation, there was massive loss of olfactory epithelium and no EOG response in non-treated IOI mice. However, in Etanercept - treated mice, regeneration of olfactory epithelium was observed. Conclusion Concomitant administration of Etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that Etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models. PMID:26932943

  12. Olfactory and solitary chemosensory cells: two different chemosensory systems in the nasal cavity of the American alligator, Alligator mississippiensis

    PubMed Central

    Hansen, Anne

    2007-01-01

    Background The nasal cavity of all vertebrates houses multiple chemosensors, either innervated by the Ist (olfactory) or the Vth (trigeminal) cranial nerve. Various types of receptor cells are present, either segregated in different compartments (e.g. in rodents) or mingled in one epithelium (e.g. fish). In addition, solitary chemosensory cells have been reported for several species. Alligators which seek their prey both above and under water have only one nasal compartment. Information about their olfactory epithelium is limited. Since alligators seem to detect both volatile and water-soluble odour cues, I tested whether different sensory cell types are present in the olfactory epithelium. Results Electron microscopy and immunocytochemistry were used to examine the sensory epithelium of the nasal cavity of the American alligator. Almost the entire nasal cavity is lined with olfactory (sensory) epithelium. Two types of olfactory sensory neurons are present. Both types bear cilia as well as microvilli at their apical endings and express the typical markers for olfactory neurons. The density of these olfactory neurons varies along the nasal cavity. In addition, solitary chemosensory cells innervated by trigeminal nerve fibres, are intermingled with olfactory sensory neurons. Solitary chemosensory cells express components of the PLC-transduction cascade found in solitary chemosensory cells in rodents. Conclusion The nasal cavity of the American alligator contains two different chemosensory systems incorporated in the same sensory epithelium: the olfactory system proper and solitary chemosensory cells. The olfactory system contains two morphological distinct types of ciliated olfactory receptor neurons. PMID:17683564

  13. Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli.

    PubMed

    Corfield, Jeremy R; Eisthen, Heather L; Iwaniuk, Andrew N; Parsons, Stuart

    2014-01-01

    The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche. PMID:25376305

  14. Olfactory-mediated stream-finding behavior of migratory adult sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Vrieze, L.A.; Bergstedt, R.A.; Sorensen, P.W.

    2011-01-01

    Stream-finding behavior of adult sea lamprey (Petromyzon marinus), an anadromous fish that relies on pheromones to locate spawning streams, was documented in the vicinity of an important spawning river in the Great Lakes. Untreated and anosmic migrating sea lampreys were implanted with acoustic transmitters and then released outside the Ocqueoc River. Lampreys swam only at night and then actively. When outside of the river plume, lampreys pursued relatively straight bearings parallel to the shoreline while making frequent vertical excursions. In contrast, when within the plume, lampreys made large turns and exhibited a weak bias towards the river mouth, which one-third of them entered. The behavior of anosmic lampreys resembled that of untreated lampreys outside of the plume, except they pursued a more northerly compass bearing. To locate streams, sea lampreys appear to employ a three-phase odor-mediated strategy that involves an initial search along shorelines while casting vertically, followed by river-water-induced turning that brings them close to the river's mouth, which they then enter using rheotaxis. This novel strategy differs from that of salmonids and appears to offer this poor swimmer adaptive flexibility and suggests ways that pheromonal odors might be used to manage this invasive species.

  15. The Generation of Olfactory Epithelial Neurospheres in vitro Predicts Engraftment Capacity following Transplantation in vivo

    PubMed Central

    Krolewski, Richard C.; Jang, Woochan; Schwob, James E.

    2011-01-01

    The stem and progenitor cells of the olfactory epithelium maintain the tissue throughout life and effectuate epithelial reconstitution after injury. We have utilized free-floating olfactory neurosphere cultures to study factors influencing proliferation, differentiation, and transplantation potency of sphere-grown cells as a first step toward using them for therapeutic purposes. Olfactory neurospheres form best and expand most when grown from neonatal epithelium, although methyl bromide-injured or normal adult material is weakly spherogenic. The spheres contain the full range of epithelial cell types as marked by cytokeratins, neuron-specific antigens, E-cadherin, Sox2, and Sox9. Globose basal cells are also prominent constituents. Media conditioned by growth of phorbol ester-stimulated, immortalized lamina propria-derived cells (LPImm) significantly increases the percentage of Neurog1eGFP (+) progenitors and immature neurons in spheres. Sphere-forming capacity resides within selected populations; FACS-purified, Neurog1eGFP (+) cells were poorly spherogenic, while preparations from ΔSox2eGFP transgenic mice that are enriched for Sox2(+) basal cells formed spheres very efficiently. Finally, we compared the potency following transplantation of cells grown in spheres vs. cells derived from adherent cultures. The sphere-derived cells engrafted and produced colonies with multiple cell types that incorporated into and resembled host epithelium; cells from adherent cultures did not. Furthermore, cells from spheres grown in conditioned media from the phorbol ester-activated LPImm line gave rise to significantly more neurons after transplantation as compared with control. The current findings demonstrate that sphere formation serves as a biomarker for engraftment capacity and multipotency of olfactory progenitors, which are requirements for their eventual translational use. PMID:21376038

  16. Immunohistochemical demonstration of salmon olfactory glutathione S-transferase class pi (N24) in the olfactory system of lacustrine sockeye salmon during ontogenesis and cell proliferation.

    PubMed

    Yanagi, S; Kudo, H; Doi, Y; Yamauchi, K; Ueda, H

    2004-06-01

    In mammals, glutathione S-transferase (GST) in the olfactory epithelium is involved in assistance of the olfactory reception by the xenobiotic metabolism. We previously reported the protein and gene expressions of salmon olfactory GST class pi (soGST) in the olfactory receptor cells (ORCs) of the salmonid fish. However, the chronological appearances of soGST in ORCs during ontogeny and cell proliferation are still unknown in this species. In this study, we performed immunohistochemistry of soGST using an antibody specific to soGST in the olfactory system (olfactory placode, olfactory pit, olfactory epithelium, olfactory nerve and olfactory bulb) of lacustrine sockeye salmon ( Oncorhynchus nerka) embryos and 5-bromo-2'-deoxyuridine (BrdU) experimental fish. The projection of olfactory nerve bundles from the olfactory pit to the presumptive olfactory bulb was identified at embryonic day 28 after fertilization. The olfactory cilia were first detected on the apical surface of ORCs at day 43. soGST-immunoreactivity was first detected within the olfactory pit cells at day 55. At 58 day, the number of soGST-immunoreactive cells increased markedly in the olfactory epithelia, and soGST-immunoreactive fibers were observed in the olfactory nerves and olfactory bulbs. By in vivo uptake of BrdU in 1-year-old fish, we observed for the first time at day 7 after labeling that the olfactory epithelia showed ORCs in which both soGST-immunoreactivity and BrdU coexisted. These results indicate that soGST is synthesized in the mature ORCs of lacustrine sockeye salmon after cell formation and differentiation. PMID:15156400

  17. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  18. Olfactory Receptor Neuron Dysfunction in Schizophrenia

    PubMed Central

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2012-01-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  19. Olfactory receptor neuron dysfunction in schizophrenia.

    PubMed

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2009-02-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  20. Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb.

    PubMed

    Liang, Yajie; Li, Kaizhen; Riecken, Kristoffer; Maslyukov, Anatoliy; Gomez-Nicola, Diego; Kovalchuk, Yury; Fehse, Boris; Garaschuk, Olga

    2016-07-01

    The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate. PMID:27174051

  1. Human Neural Cells Transiently Express Reelin during Olfactory Placode Development

    PubMed Central

    Antal, M. Cristina; Samama, Brigitte; Ghandour, M. Said; Boehm, Nelly

    2015-01-01

    Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

  2. Human Neural Cells Transiently Express Reelin during Olfactory Placode Development.

    PubMed

    Antal, M Cristina; Samama, Brigitte; Ghandour, M Said; Boehm, Nelly

    2015-01-01

    Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

  3. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    NASA Astrophysics Data System (ADS)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  4. Slc15a1 is involved in the transport of synthetic F5-peptide into the seminiferous epithelium in adult rat testes

    PubMed Central

    Su, Linlin; Zhang, Yufei; Cheng, Yan C.; Lee, Will M.; Ye, Keping; Hu, Dahai

    2015-01-01

    Spermiation and BTB restructuring, two critical cellular events that occur across seminiferous epithelium in mammalian testis during spermatogenesis, are tightly coordinated by biologically active peptides released from laminin chains. Our earlier study reported that F5-peptide, synthesized based on a stretch of 50 amino acids within laminin-γ3 domain IV, could reversibly induce the impairment of spermatogenesis, disruption of BTB integrity, and germ cell loss, and thus is a promising male contraceptive. However, how F5-peptide when administered intratesticularly enters seminiferous tubules and exerts effects beyond BTB is currently unknown. Here we demonstrated that Slc15a1, a peptide transporter also known as Pept1, was predominantly present in peritubular myoid cells, interstitial Leydig cells, vascular endothelial cells and germ cells, while absent in Sertoli cells or BTB site. The steady-state protein level of Slc15a1 in adult rat testis was not affected by F5-peptide treatment. Knockdown of Slc15a1 by in vivo RNAi in rat testis was shown to prevent F5-peptide induced disruptive effects on spermatogenesis. This study suggests that Slc15a1 is involved in the transport of synthetic F5-peptide into seminiferous epithelium, and thus Slc15a1 is a novel target in testis that could be genetically modified to improve the bioavailability of F5-peptide as a prospective male contraceptive. PMID:26537751

  5. Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

    PubMed Central

    Schmidt, Manfred; Derby, Charles D.

    2013-01-01

    New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast’s microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. PMID:21523781

  6. Investigation of olfactory function in a Panx1 knock out mouse model.

    PubMed

    Kurtenbach, Stefan; Whyte-Fagundes, Paige; Gelis, Lian; Kurtenbach, Sarah; Brazil, Emerson; Zoidl, Christiane; Hatt, Hanns; Shestopalov, Valery I; Zoidl, Georg

    2014-01-01

    Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1(-/-) mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1(-/-) mice. Further, functional analysis of Panx1(-/-) animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1(-/-) mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1(-/-) mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system. PMID:25309319

  7. Investigation of olfactory function in a Panx1 knock out mouse model

    PubMed Central

    Kurtenbach, Stefan; Whyte-Fagundes, Paige; Gelis, Lian; Kurtenbach, Sarah; Brazil, Émerson; Zoidl, Christiane; Hatt, Hanns; Shestopalov, Valery I.; Zoidl, Georg

    2014-01-01

    Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1−/− mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1−/− mice. Further, functional analysis of Panx1−/− animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1−/− mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1−/− mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system. PMID:25309319

  8. Phylogenic studies on the olfactory system in vertebrates.

    PubMed

    Taniguchi, Kazuyuki; Taniguchi, Kazumi

    2014-06-01

    The olfactory receptor organs and their primary centers are classified into several types. The receptor organs are divided into fish-type olfactory epithelium (OE), mammal-type OE, middle chamber epithelium (MCE), lower chamber epithelium (LCE), recess epithelium, septal olfactory organ of Masera (SO), mammal-type vomeronasal organ (VNO) and snake-type VNO. The fish-type OE is observed in flatfish and lungfish, while the mammal-type OE is observed in amphibians, reptiles, birds and mammals. The MCE and LCE are unique to Xenopus and turtles, respectively. The recess epithelium is unique to lungfish. The SO is observed only in mammals. The mammal-type VNO is widely observed in amphibians, lizards and mammals, while the snake-type VNO is unique to snakes. The VNO itself is absent in turtles and birds. The mammal-type OE, MCE, LCE and recess epithelium seem to be descendants of the fish-type OE that is derived from the putative primitive OE. The VNO may be derived from the recess epithelium or fish-type OE and differentiate into the mammal-type VNO and snake-type VNO. The primary olfactory centers are divided into mammal-type main olfactory bulbs (MOB), fish-type MOB and mammal-type accessory olfactory bulbs (AOB). The mammal-type MOB first appears in amphibians and succeeds to reptiles, birds and mammals. The fish-type MOB, which is unique to fish, may be the ancestor of the mammal-type MOB. The mammal-type AOB is observed in amphibians, lizards, snakes and mammals and may be the remnant of the fish-type MOB. PMID:24531771

  9. Phylogenic Studies on the Olfactory System in Vertebrates

    PubMed Central

    TANIGUCHI, Kazuyuki; TANIGUCHI, Kazumi

    2014-01-01

    ABSTRACT The olfactory receptor organs and their primary centers are classified into several types. The receptor organs are divided into fish-type olfactory epithelium (OE), mammal-type OE, middle chamber epithelium (MCE), lower chamber epithelium (LCE), recess epithelium, septal olfactory organ of Masera (SO), mammal-type vomeronasal organ (VNO) and snake-type VNO. The fish-type OE is observed in flatfish and lungfish, while the mammal-type OE is observed in amphibians, reptiles, birds and mammals. The MCE and LCE are unique to Xenopus and turtles, respectively. The recess epithelium is unique to lungfish. The SO is observed only in mammals. The mammal-type VNO is widely observed in amphibians, lizards and mammals, while the snake-type VNO is unique to snakes. The VNO itself is absent in turtles and birds. The mammal-type OE, MCE, LCE and recess epithelium seem to be descendants of the fish-type OE that is derived from the putative primitive OE. The VNO may be derived from the recess epithelium or fish-type OE and differentiate into the mammal-type VNO and snake-type VNO. The primary olfactory centers are divided into mammal-type main olfactory bulbs (MOB), fish-type MOB and mammal-type accessory olfactory bulbs (AOB). The mammal-type MOB first appears in amphibians and succeeds to reptiles, birds and mammals. The fish-type MOB, which is unique to fish, may be the ancestor of the mammal-type MOB. The mammal-type AOB is observed in amphibians, lizards, snakes and mammals and may be the remnant of the fish-type MOB. PMID:24531771

  10. Developmental, tract-tracing and immunohistochemical study of the peripheral olfactory system in a basal vertebrate: insights on Pax6 neurons migrating along the olfactory nerve.

    PubMed

    Quintana-Urzainqui, Idoia; Rodríguez-Moldes, Isabel; Candal, Eva

    2014-01-01

    The olfactory system represents an excellent model for studying different aspects of the development of the nervous system ranging from neurogenesis to mechanisms of axon growth and guidance. Important findings in this field come from comparative studies. We have analyzed key events in the development of the olfactory system of the shark Scyliorhinus canicula by combining immunohistochemical and tract-tracing methods. We describe for the first time in a cartilaginous fish an early population of pioneer HuC/D-immunoreactive (ir) neurons that seemed to delaminate from the olfactory pit epithelium and migrate toward the telencephalon before the olfactory nerve was identifiable. A distinct, transient cell population, namely the migratory mass, courses later on in apposition to the developing olfactory nerve. It contains olfactory ensheathing glial (GFAP-ir) cells and HuC/D-ir neurons, some of which course toward an extrabulbar region. We also demonstrate that Pax6-ir cells coursing along the developing olfactory pathways in S. canicula are young migrating (HuC/D and DCX-ir) neurons of the migratory mass that do not form part of the terminal nerve pathway. Evidences that these Pax6 neurons originate in the olfactory epithelium are also reported. As Pax6 neurons in the olfactory epithelium show characteristics of olfactory receptor neurons, and migrating Pax6-ir neurons formed transient corridors along the course of olfactory axons at the entrance of the olfactory bulb, we propose that these neurons could play a role as guideposts for axons of olfactory receptor neurons growing toward the olfactory bulb. PMID:23224251

  11. Pax6 Is Essential for the Maintenance and Multi-Lineage Differentiation of Neural Stem Cells, and for Neuronal Incorporation into the Adult Olfactory Bulb

    PubMed Central

    Curto, Gloria G.; Nieto-Estévez, Vanesa; Hurtado-Chong, Anahí; Valero, Jorge; Gómez, Carmela; Alonso, José R.; Weruaga, Eduardo

    2014-01-01

    The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/SeyDey mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin+-cell proliferation in vivo, as well as self-renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/SeyDey progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population. PMID:25117830

  12. Olfactory Signal Transduction in the Mouse Septal Organ

    PubMed Central

    Ma, Minghong; Grosmaitre, Xavier; Iwema, Carrie L.; Baker, Harriet; Greer, Charles A.; Shepherd, Gordon M.

    2008-01-01

    The septal organ, a distinct chemosensory organ observed in the mammalian nose, is essentially a small island of olfactory neuroepithelium located bilaterally at the ventral base of the nasal septum. Virtually nothing is known about its physiological properties and function. To understand the nature of the sensory neurons in this area, we studied the mechanisms underlying olfactory signal transduction in these neurons. The majority of the sensory neurons in the septal organ express olfactory-specific G-protein and adenylyl cyclase type III, suggesting that the cAMP signaling pathway plays a critical role in the septal organ as in the main olfactory epithelium (MOE). This is further supported by patch-clamp recordings from individual dendritic knobs of the sensory neurons in the septal organ. Odorant responses can be mimicked by an adenylyl cyclase activator and a phosphodiesterase inhibitor, and these responses can be blocked by an adenylyl cyclase inhibitor. There is a small subset of cells in the septal organ expressing a cGMP-stimulated phosphodiesterase (phosphodiesterase 2), a marker for the guanylyl cyclase-D subtype sensory neurons identified in the MOE. The results indicate that the septal organ resembles the MOE in major olfactory signal transduction pathways, odorant response properties, and projection to the main olfactory bulb. Molecular and functional analysis of the septal organ, which constitutes ~1% of the olfactory epithelium, will provide new insights into the organization of the mammalian olfactory system and the unique function this enigmatic organ may serve. PMID:12514230

  13. 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. PMID:25995474

  14. Targeted Overexpression of TGF-α in the Corneal Epithelium of Adult Transgenic Mice Induces Changes in Anterior Segment Morphology and Activates Noncanonical Wnt Signaling

    PubMed Central

    Yuan, Yong; Yeh, Lung-Kun; Liu, Hongshan; Yamanaka, Osamu; Hardie, William D.; Kao, Winston W.-Y.; Liu, Chia-Yang

    2013-01-01

    Purpose. Transforming growth factor-alpha (TGF-α) transduces its signal through the epidermal growth factor receptor and is essential for corneal epithelial homeostasis. Previous studies have demonstrated that overexpression of TGF-α in the developing eye leads to anterior segment dysgenesis. However, the underlying mechanisms remain unclear. Here we examined the effects of TGF-α overexpression on adult ocular surface homeostasis. Methods. Binary Tet-On transgenic Krt12rtTA/tet-O-TGF-α mice were subjected to doxycycline (Dox) induction to overexpress TGF-α in the corneal epithelium. Intraocular pressure (IOP) was measured by noninvasive tonometry. The enucleated eyes of the experimental mice were subjected to histopathology, immunohistochemistry, and biochemistry examination. Results. Histologic and immunofluorescent examination showed that double-transgenic mice overexpressing TGF-α manifested peripheral anterior synechiae. Elevation of IOP, activation of glial cells, and loss of retinal ganglion cells were also observed. Quantitative real-time PCR revealed that the expressions of genes (RXRα, PITX2, and FOXC1) related to anterior segment dysgenesis were downregulated. Canonical Wnt signaling was suppressed, whereas noncanonical Wnt ligands (Wnt4 and Wnt5a) were upregulated. Increased myosin light chain phosphorylation suggested that noncanonical Wnt signaling is activated in affected eyes. Conclusions. Overexpression of TGF-α in the corneal epithelium induces changes in anterior segment morphology. Corneal endothelial abnormalities are associated with the activation of the noncanonical Wnt and RhoA/ROCK signaling axis, indicating a potential application of RhoA/ROCK inhibitors as a therapeutic strategy for certain types of secondary angle-closure glaucoma. PMID:23412089

  15. The lack of protective effects of tea supplementation on liver and jejunal epithelium in adult rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-11-01

    Adult rats at the age of 12 weeks were divided into the control group and groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. The diet (except that for the control) was mixed with 7 mg Cd/kg and 50 mg Pb/kg. The experiment lasted 12 weeks. Basal haematology and plasma biochemical parameters as well as the histomorphometrical parameters of jejunal epithelium and liver were determined. The lowest body mass was found in the RT and WT groups. Some functional (increased plasma ALT and AST, and the de Ritis coefficient) and structural changes in the liver (slight fatty degenerative changes, an increase in the intercellular space) were evident irrespective of the type of tea in the Cd and Pb poisoned rats. This toxic effect was visible especially in rats drinking black or red tea. However, the rats had no elevated LDH and ALT activities. The highest content of Cd and Pb in the liver and blood plasma was found in rats drinking red tea. Based on the results obtained, it is clear that long-term exposure of adult rats with a mature intestinal barrier to Cd and Pb contamination, under higher exposure conditions than the current estimates of weekly exposure of the general population to Cd and Pb through diet, causes a toxic effect, especially in the liver, and can change the structure of intestinal mucosa, irrespective of tea administration. PMID:26410089

  16. 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

  17. Mini-review: Making scent of the presence and local translation of odorant receptor mRNAs in olfactory axons

    PubMed Central

    Dubacq, Caroline; Fouquet, Coralie; Trembleau, Alain

    2016-01-01

    Rodents contain in their genome more than 1,000 functional odorant receptor genes, which are specifically expressed by the olfactory sensory neurons projecting from the olfactory epithelium to the olfactory bulb. Strong evidence for the presence and local translation of odorant receptor mRNAs in the axon of olfactory sensory neurons was obtained, but no function has been assigned to these axonal mRNAs yet. The aim of this review is to discuss the evidence for the presence and local translation of odorant receptor mRNAs in olfactory sensory axons, and to speculate on their possible function in the wiring of the mouse olfactory sensory projections. PMID:23959692

  18. Calcium-binding protein parvalbumin-immunoreactive neurons in the rat olfactory bulb. 1. Distribution and structural features in adult rat.

    PubMed

    Kosaka, K; Heizmann, C W; Kosaka, T

    1994-01-01

    The laminar distribution and morphological features of parvalbumin-immunoreactive [PV(+)] neurons, one of the subpopulations of GABAergic neurons, were studied in the rat olfactory bulb at a light microscopic level. In the main olfactory bulb of adult rats, PV(+) neurons were mainly located in the external plexiform layer (EPL), and a few were scattered in the glomerular layer (GL), mitral cell layer (ML), and granule cell layer (GRL); whereas PV(+) neurons were rarely seen in the accessory olfactory bulb. The inner and outer sublayers of the EPL (ISL and OSL) appeared to be somewhat different in the distribution of PV(+) somata and features of PV(+) processes. PV(+) somata were located throughout the OSL, and PV(+) processes intermingled with one another, making a dense meshwork in the OSL; whereas, in the ISL, PV(+) somata were mainly located near the inner border of the EPL, and PV(+) processes made a sparser meshwork than that in the OSL. PV(+) neurons in the EPL were apparently heterogeneous in their structural features and appeared to be classifiable into several groups. Among them there appeared five distinctive types of PV(+) neurons. The most prominent group of PV(+) neurons in the OSL were superficial short-axon cells, located in the superficial portion of this sublayer and giving rise to relatively thick processes, in horizontal or oblique directions, which usually bore spines and varicosities. Another prominent group of PV(+) neurons extended several short, branched dendrites with spines and varicosities, which appeared to intermingle with one another, making a relatively small, spherical or ovoid dendritic field around the cell bodies; most of them resembled Van Gehuchten cells reported in previous Golgi studies. A third distinctive and most numerous group of PV(+) neurons were of the multipolar type; their somata and processes were located throughout the EPL. Their relatively smooth processes with frequent varicosities and a few spines were extended

  19. Direct transport of inhaled xylene and its metabolites from the olfactory mucosa to the glomeruli of the olfactory bulbs

    SciTech Connect

    Lewis, J.L.; Dahl, A.R.; Kracko, D.A.

    1994-11-01

    The olfactory epithelium is a unique tissue in that single receptor neurons have dendrites in contact with the external environment at the nasal airway, and axon terminals that penetrate the cribriform plate and synapse in the olfactory bulb. The Central Nervous System (CNS) is protected from systematically circulating toxicants by a blood-brain barrier primarily composed of tight junctions between endothelial cells in cerebral vessels and a high metabolic capacity within these cells. No such barrier has yet been defined to protect the CNS from inhaled toxicants. Because all inhalants do not seem to access the CNS directly, a nose-brain barrier seems plausible. The purpose of the work described here is to determine whether or not a nose-brain barrier exists and to define its components. Although such a barrier is likely to be multi-faceted, the present work focuses only on the importance of gross histologic and metabolic characteristics of the olfactory epithelium in olfactory transport.

  20. Development of the olfactory system in a wallaby (Macropus eugenii).

    PubMed

    Ashwell, K W S; Marotte, L R; Cheng, Gang

    2008-01-01

    We used carbocyanine dye tracing techniques in conjunction with hematoxylin and eosin staining, immunohistochemistry for GAP-43, and tritiated thymidine autoradiography to examine the development of the olfactory pathways in early pouch young tammar wallabies (Macropus eugenii). The overarching aim was to test the hypothesis that the olfactory system of newborn tammars is sufficiently mature at birth to contribute to the guidance of the pouch young to the nipple. Although GAP-43 immunoreactive fibers emerge from the olfactory epithelium and enter the olfactory bulb at birth, all other components of the olfactory pathway in newborn tammars are very immature at birth, postnatal day (P0). In particular, maturation of the vomeronasal organ and its projections to the accessory olfactory bulb appears to be delayed until P5 and the olfactory bulb is poorly differentiated until P12, with glomerular formation delayed until P25. The lateral olfactory tract is also very immature at birth with pioneer axons having penetrated only the most rostral portion of the piriform lobe. Interestingly, there were some early (P0) projections from the olfactory epithelium to the medial septal region and lamina terminalis (by the terminal nerve) and to olfactory tubercle and basal forebrain. The former of these is presumably serving the transfer of LHRH(+) neurons to the forebrain, as seen in eutherians, but neither of these very early pathways is sufficiently robust or connected to the more caudal neuraxis to play a role in nipple finding. Tritiated thymidine autoradiography confirmed that most piriform cortex pyramidal neurons are generated in the first week of life and are unlikely to be able to contribute to circuitry guiding the climb to the pouch. Our findings lead us to reject the hypothesis that olfactory projections contribute to guidance of the newborn tammar to the pouch and nipple. It appears far more likely that the trigeminal pathways play a significant role in this behavior

  1. Morphological and electrophysiological examination of olfactory sensory neurons during the early developmental prolarval stage of the sea lamprey Petromyzon marinus L

    USGS Publications Warehouse

    Zielinski, B.S.; Fredricks, Keith; McDonald, R.; Zaidi, A.U.

    2005-01-01

    This study examined olfactory sensory neuron morphology and physiological responsiveness in newly hatched sea lamprey, Petromyzon marinus L. These prolarvae hatch shortly after neural tube formation, and stay within nests for approximately 18 days, before moving downstream to silty areas where they burrow, feed and pass to the larval stage. To explore the possibility that the olfactory system is functioning during this prolarval stage, morphological and physiological development of olfactory sensory neurons was examined. The nasal cavity contained an olfactory epithelium with ciliated olfactory sensory neurons. Axons formed aggregates in the basal portion of the olfactory epithelium and spanned the narrow distance between the olfactory epithelium and the brain. The presence of asymmetric synapses with agranular vesicles within fibers in the brain, adjacent to the olfactory epithelium suggests that there was synaptic connectivity between olfactory sensory axons and the brain. Neural recordings from the surface of the olfactory epithelium showed responses following the application of L-arginine, taurocholic acid, petromyzonol sulfate (a lamprey migratory pheromone), and water conditioned by conspecifics. These results suggest that lampreys may respond to olfactory sensory input during the prolarval stage. ?? 2006 Springer Science + Business Media, LLC.

  2. Odorant Metabolism Catalyzed by Olfactory Mucosal Enzymes Influences Peripheral Olfactory Responses in Rats

    PubMed Central

    Thiebaud, Nicolas; Veloso Da Silva, Stéphanie; Jakob, Ingrid; Sicard, Gilles; Chevalier, Joëlle; Ménétrier, Franck; Berdeaux, Olivier; Artur, Yves; Heydel, Jean-Marie; Le Bon, Anne-Marie

    2013-01-01

    A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat OM and assessed the impact of this metabolism on peripheral olfactory responses. Rat OM was found to efficiently metabolize quinoline, coumarin and isoamyl acetate. Quinoline and coumarin are metabolized by CYPs whereas isoamyl acetate is hydrolyzed by carboxylesterases. Electro-olfactogram (EOG) recordings revealed that the hydroxylated metabolites derived from these odorants elicited lower olfactory response amplitudes than the parent molecules. We also observed that glucurono-conjugated derivatives induced no olfactory signal. Furthermore, we demonstrated that the local application of a CYP inhibitor on rat olfactory epithelium increased EOG responses elicited by quinoline and coumarin. Similarly, the application of a carboxylesterase inhibitor increased the EOG response elicited by isoamyl acetate. This increase in EOG amplitude provoked by XME inhibitors is likely due to enhanced olfactory sensory neuron activation in response to odorant accumulation. Taken together, these findings strongly suggest that biotransformation of odorant molecules by enzymes localized to the olfactory mucosa may change the odorant’s stimulating properties and may facilitate the clearance of odorants to avoid receptor saturation. PMID:23555703

  3. Adiponectin enhances the responsiveness of the olfactory system.

    PubMed

    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

  4. 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

  5. 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. PMID:27059760

  6. Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons.

    PubMed

    McLean, J H; Shipley, M T

    1988-10-01

    The developmental expression of tyrosine hydroxylase (TOH) was studied in a large, specific population of dopaminergic (DA) neurons in the main olfactory bulb (MOB) of the rat. These DA neurons comprise an anatomically distinctive population that has been well characterized in the adult hamster (Davis and Macrides, 1983) and rat (Halasz et al., 1981; Baker et al., 1983, 1984). We addressed a basic question in developmental neurobiology: What factors regulate the expression of neuronal transmitter phenotype during development? Olfactory bulb DA neurons are born in the ventricular and subependymal zones and migrate through all intervening layers to the most superficial layer in the bulb (Altman, 1969; Bayer, 1983). The time of TOH expression in these neurons was determined using immunohistochemistry and light microscopic image-analysis techniques. The results indicate that TOH phenotype is not expressed when the cells are born in the subependymal zone nor during their migration to the periglomerular region but only after they reached their final destination, the glomerular layer. This suggests that epigenetic factors associated with the glomeruli initiate the expression of the key transmitter synthesizing enzyme in these neurons. Primary olfactory neurons in the nasal epithelium project exclusively to glomeruli of the MOB; removal of this input in adult rats (Kawano and Margolis, 1982; Baker et al., 1983, 1984), mice (Nadi et al., 1981; Baker et al., 1983), dogs (Nadi et al., 1981), and hamsters (Kream et al., 1984) appears to down-regulate the expression of the TOH in periglomerular cells. The present results suggested that the input from the primary olfactory nerve is also necessary for the initial expression of the TOH phenotype. In support of this notion, we found that lesions of the olfactory nerve during the first postnatal week caused a significant reduction in the number of TOH-positive juxtaglomerular neurons in the following weeks. Thus, the olfactory nerve

  7. Olfactory neuroblastoma

    SciTech Connect

    O'Connor, T.A.; McLean, P.; Juillard, G.J.; Parker, R.G.

    1989-06-15

    Fifteen patients with olfactory neuroblastoma were treated during the 17-year period of 1969 to 1986. Data was analyzed with respect to age at presentation, sex, presenting signs and symptoms, stage, and results of treatment. Age ranged from 4 to 67 years with the median age being 27 years. Median follow-up was 8 years. Local control was achieved in nine of nine patients or 100% with successful surgical resection, i.e., minimal residual disease, followed by postoperative radiation therapy (45 to 65 Gy) was employed. There were no distant failures when the primary site was controlled. Regional lymph node metastases were infrequent: only 13% (two of 15 patients) presented with positive nodes. Three of four patients treated initially with surgery alone had a local recurrence, two of which were successfully salvaged by combined therapy. There were four patients treated with radiation therapy alone: three had persistent disease after radiation therapy, and one patient was controlled with 65 Gy. Olfactory neuroblastoma has a propensity to recur locally when treated with surgery alone. The authors' experience suggests excellent local control can be achieved with surgery immediately followed by radiation therapy. Thus the authors recommend planned combined treatment for all resectable lesions.

  8. Impaired sense of smell and altered olfactory system in RAG-1−∕− immunodeficient mice

    PubMed Central

    Rattazzi, Lorenza; Cariboni, Anna; Poojara, Ridhika; Shoenfeld, Yehuda; D'Acquisto, Fulvio

    2015-01-01

    Immune deficiencies are often associated with a number of physical manifestations including loss of sense of smell and an increased level of anxiety. We have previously shown that T and B cell-deficient recombinase activating gene (RAG-1)−∕− knockout mice have an increased level of anxiety-like behavior and altered gene expression involved in olfaction. In this study, we expanded these findings by testing the structure and functional development of the olfactory system in RAG-1−∕− mice. Our results show that these mice have a reduced engagement in different types of odors and this phenotype is associated with disorganized architecture of glomerular tissue and atrophy of the main olfactory epithelium. Most intriguingly this defect manifests specifically in adult age and is not due to impairment in the patterning of the olfactory neuron staining at the embryo stage. Together these findings provide a formerly unreported biological evidence for an altered function of the olfactory system in RAG-1−∕− mice. PMID:26441494

  9. Histochemical study of the olfactory mucosae of the horse.

    PubMed

    Lee, Kwang-Hyup; Park, Changnam; Bang, Hyojin; Ahn, Meejung; Moon, Changjong; Kim, Seungjoon; Shin, Taekyun

    2016-05-01

    The olfactory mucosae of the horse were examined by using histology and lectin histochemistry to characterize the carbohydrate sugar residues therein. Histological findings revealed that olfactory epithelium (OE) consisted of both olfactory marker protein (OMP)- and protein gene product (PGP) 9.5-positive receptor cells, supporting cells and basal cells with intervening secretory ducts from Bowman's glands. Mucus histochemistry showed that Bowman's gland acini contain periodic acid-Schiff (PAS) reagent-positive neutral mucins and alcian blue pH 2.5-positive mucosubstances. Lectin histochemistry revealed that a variety of carbohydrate sugar residues, including N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, fucose and complex type N-glycan groups, are present in the various cell types in the olfactory mucosa at varying levels. Collectively, this is the first descriptive study of horse olfactory mucosa to characterize carbohydrate sugar residues in the OE and Bowman's glands. PMID:27040092

  10. Protein kinase C sensitizes olfactory adenylate cyclase.

    PubMed

    Frings, S

    1993-02-01

    Effects of neurotransmitters on cAMP-mediated signal transduction in frog olfactory receptor cells (ORCs) were studied using in situ spike recordings and radioimmunoassays. Carbachol, applied to the mucosal side of olfactory epithelium, amplified the electrical response of ORCs to cAMP-generating odorants, but did not affect unstimulated cells. A similar augmentation of odorant response was observed in the presence of phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC). The electrical response to forskolin, an activator of adenylate cyclase (AC), was also enhanced by PDBu, and it was attenuated by the PKC inhibitor Goe 6983. Forskolin-induced accumulation of cAMP in olfactory tissue was potentiated by carbachol, serotonin, and PDBu to a similar extent. Potentiation was completely suppressed by the PKC inhibitors Goe 6983, staurosporine, and polymyxin B, suggesting that the sensitivity of olfactory AC to stimulation by odorants and forskolin was increased by PKC. Experiments with deciliated olfactory tissue indicated that sensitization of AC was restricted to sensory cilia of ORCs. To study the effects of cell Ca2+ on these mechanisms, the intracellular Ca2+ concentration of olfactory tissue was either increased by ionomycin or decreased by BAPTA/AM. Increasing cell Ca2+ had two effects on cAMP production: (a) the basal cAMP production was enhanced by a mechanism sensitive to inhibitors of calmodulin; and (b) similar to phorbol ester, cell Ca2+ caused sensitization of AC to stimulation by forskolin, an effect sensitive to Goe 6983. Decreasing cell Ca2+ below basal levels rendered AC unresponsive to stimulation by forskolin. These data suggest that a crosstalk mechanism is functional in frog ORCs, linking the sensitivity of AC to the activity of PKC. At increased activity of PKC, olfactory AC becomes more responsive to stimulation by odorants, forskolin, and cell Ca2+. Neurotransmitters appear to use this crosstalk mechanism to regulate olfactory

  11. Magnetite-Based Magnetoreceptor Cells in the Olfactory Organ of Rainbow Trout and Zebrafish

    NASA Astrophysics Data System (ADS)

    Kirschvink, J. L.; Cadiou, H.; Dixson, A. D.; Eder, S.; Kobayashi, A.; McNaughton, P. A.; Muhamad, A. N.; Raub, T. D.; Walker, M. M.; Winklhofer, M.; Yuen, B. B.

    2011-12-01

    Many vertebrate and invertebrate animals have a geomagnetic sensory system, but the biophysics and anatomy of how magnetic stimuli are transduced to the nervous system is a challenging problem. Previous work in our laboratories identified single-domain magnetite chains in olfactory epithelium in cells proximal to the ros V nerve, which, in rainbow trout, responds to magnetic fields. Our objectives are to characterize these magnetite-containing cells and determine whether they form part of the mechanism of magnetic field transduction in teleost fishes, as a model for other Vertebrates. Using a combination of reflection mode confocal microscopy and a Prussian Blue technique modified to stain specifically for magnetite, our Auckland group estimated that both juvenile rainbow trout (ca. 7 cm total length) olfactory rosettes have ~200 magnetite-containing cells. The magnetite present in two types of cells within the olfactory epithelium appears to be arranged in intracellular chains. All of our groups (Munich, Auckland, Cambridge and Caltech) have obtained different types of structural evidence that magnetite chains closely associate with the plasma membrane in the cells, even in disaggregated tissues. In addition, our Cambridge group used Ca2+ imaging to demonstrate a clear response by individual magnetite-containing cells to a step change in the intensity of the external magnetic field and a slow change in Ca2+ activity when the external magnetic field was cancelled. In the teleost, zebrafish (Danio rerio), a small (~4 cm adult length in captivity) genetic and developmental biology model organism, our Caltech group detected ferromagnetic material throughout the body, but concentrated in the rostral trunk, using NRM and IRM scans of whole adults. Our analysis suggests greater than one million, 80-100 nm crystals, with Lowrie-Fuller curves strongly consistent with single-domain magnetite in 100-100,000 magnetocytes. Ferromagentic resonance (FMR) spectra show crystals

  12. Identification of G protein α subunits in the main olfactory system and vomeronasal system of the Japanese Striped snake, Elaphe quadrivirgata.

    PubMed

    Kondoh, Daisuke; Koshi, Katsuo; Ono, Hisaya K; Sasaki, Kuniaki; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2013-01-01

    In the olfactory system, G proteins couple to the olfactory receptors, and G proteins expressed in the main olfactory system and vomeronasal system vary according to animal species. In this study, G protein α subunits expressed in the main olfactory system and vomeronasal system of the snake were identified by immunohistochemistry. In the olfactory epithelium, only anti-Gαolf/s antibody labeled the cilia of the receptor cells. In the vomeronasal epithelium, only anti-Gαo antibody labeled the microvilli of the receptor cells. In the accessory olfactory bulb, anti-Gαo antibody stained the whole glomerular layer. These results suggest that the main olfactory system and the vomeronasal system of the snake express Gαolf and Gαo as G proteins coupling to the olfactory receptors, respectively. PMID:23090693

  13. Over-Expression of hNGF in Adult Human Olfactory Bulb Neural Stem Cells Promotes Cell Growth and Oligodendrocytic Differentiation

    PubMed Central

    Marei, Hany E. S.; Althani, Asmaa; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Bernardini, Camilla; Michetti, Fabrizio; Barba, Marta; Pescatori, Mario; Maira, Giulio; Paldino, Emanuela; Manni, Luigi; Casalbore, Patrizia; Cenciarelli, Carlo

    2013-01-01

    The adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, however effective delivery of NGF into the CNS parenchyma is still challenging due mainly to its limited ability to cross the blood–brain barrier, and intolerable side effects if administered into the brain ventricular system. An effective method to ensure delivery of NGF into the parenchyma of CNS is the genetic modification of NSC to overexpress NGF gene. Overexpression of NGF in adult human OBNSC is expected to alter their proliferation and differentiation nature, and thus might enhance their therapeutic potential. In this study, we genetically modified adult human OBNS/PC to overexpress human NGF (hNGF) and green fluorescent protein (GFP) genes to provide insight about the effects of hNGF and GFP genes overexpression in adult human OBNS/PC on their in vitro multipotentiality using DNA microarray, immunophenotyping, and Western blot (WB) protocols. Our analysis revealed that OBNS/PC-GFP and OBNS/PC-GFP-hNGF differentiation is a multifaceted process involving changes in major biological processes as reflected in alteration of the gene expression levels of crucial markers such as cell cycle and survival markers, stemness markers, and differentiation markers. The differentiation of both cell classes was also associated with modulations of key signaling pathways such MAPK signaling pathway, ErbB signaling pathway, and neuroactive ligand-receptor interaction pathway for OBNS/PC-GFP, and axon guidance, calcium channel, voltage-dependent, gamma subunit 7 for OBNS/PC-GFP-hNGF as revealed by GO and KEGG. Differentiated OBNS/PC-GFP-hNGF displayed extensively branched cytoplasmic processes, a significant faster growth rate and up modulated the expression of oligodendroglia precursor cells

  14. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system

    PubMed Central

    Garaffo, Giulia; Conte, Daniele; Provero, Paolo; Tomaiuolo, Daniela; Luo, Zheng; Pinciroli, Patrizia; Peano, Clelia; D'Atri, Ilaria; Gitton, Yorick; Etzion, Talya; Gothilf, Yoav; Gays, Dafne; Santoro, Massimo M.; Merlo, Giorgio R.

    2015-01-01

    During neuronal development and maturation, microRNAs (miRs) play diverse functions ranging from early patterning, proliferation and commitment to differentiation, survival, homeostasis, activity and plasticity of more mature and adult neurons. The role of miRs in the differentiation of olfactory receptor neurons (ORNs) is emerging from the conditional inactivation of Dicer in immature ORN, and the depletion of all mature miRs in this system. Here, we identify specific miRs involved in olfactory development, by focusing on mice null for Dlx5, a homeogene essential for both ORN differentiation and axon guidance and connectivity. Analysis of miR expression in Dlx5−/− olfactory epithelium pointed to reduced levels of miR-9, miR-376a and four miRs of the -200 class in the absence of Dlx5. To functionally examine the role of these miRs, we depleted miR-9 and miR-200 class in reporter zebrafish embryos and observed delayed ORN differentiation, altered axonal trajectory/targeting, and altered genesis and position of olfactory-associated GnRH neurons, i.e. a phenotype known as Kallmann syndrome in humans. miR-9 and miR-200-class negatively control Foxg1 mRNA, a fork-head transcription factor essential for development of the olfactory epithelium and of the forebrain, known to maintain progenitors in a stem state. Increased levels of z-foxg1 mRNA resulted in delayed ORN differentiation and altered axon trajectory, in zebrafish embryos. This work describes for the first time the role of specific miR (-9 and -200) in olfactory/GnRH development, and uncovers a Dlx5–Foxg1 regulation whose alteration affects receptor neuron differentiation, axonal targeting, GnRH neuron development, the hallmarks of the Kallmann syndrome. PMID:25937343

  15. Kappe neurons, a novel population of olfactory sensory neurons

    PubMed Central

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system. PMID:24509431

  16. Kappe neurons, a novel population of olfactory sensory neurons

    NASA Astrophysics Data System (ADS)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  17. Transduction proteins of olfactory receptor cells: identification of guanine nucleotide binding proteins and protein kinase C

    SciTech Connect

    Anholt, R.R.H.; Mumby, S.M.; Stoffers, D.A.; Girard, P.R.; Kuo, J.F.; Snyder, S.H.

    1987-02-10

    The authors have analyzed guanine nucleotide binding proteins (G-proteins) in the olfactory epithelium of Rana catesbeiana using subunit-specific antisera. The olfactory epithelium contained the ..cap alpha.. subunits of three G-proteins, migrating on polyacrylamide gels in SDS with apparent molecular weights of 45,000, 42,000, and 40,000, corresponding to G/sub s/, G/sub i/, and G/sub o/, respectively. A single ..beta.. subunit with an apparent molecular weight of 36,000 was detected. An antiserum against the ..cap alpha.. subunit of retinal transducin failed to detect immunoreactive proteins in olfactory cilia detached from the epithelium. The olfactory cilia appeared to be enriched in immunoreactive G/sub s..cap alpha../ relative to G/sub ichemically bond/ and G/sub ochemically bond/ when compared to membranes prepared from the olfactory epithelium after detachment of the cilia. Bound antibody was detected by autoradiography after incubation with (/sup 125/I)protein. Immunohistochemical studies using an antiserum against the ..beta.. subunit of G-proteins revealed intense staining of the ciliary surface of the olfactory epithelium and of the axon bundles in the lamina propria. In contrast, an antiserum against a common sequence of the ..cap alpha.. subunits preferentially stained the cell membranes of the olfactory receptor cells and the acinar cells of Bowman's glands and the deep submucosal glands. In addition to G-proteins, they have identified protein kinase C in olfactory cilia via a protein kinase C specific antiserum and via phorbol ester binding. However, in contrast to the G-proteins, protein kinase C occurred also in cilia isolated from respiratory epithelium.

  18. Intracellular trafficking of a tagged and functional mammalian olfactory receptor.

    PubMed

    Ivic, Lidija; Zhang, Cen; Zhang, Xinmin; Yoon, Sung Ok; Firestein, Stuart

    2002-01-01

    Tagged G-protein-coupled receptors (GPCRs) have been used to facilitate intracellular visualization of these receptors. We have used a combination of adenoviral vector gene transfer and tagged olfactory receptors to help visualize mammalian olfactory receptor proteins in the normal olfactory epithelium of rats, and in cell culture. Three recombinant adenoviral vectors were generated carrying variously tagged versions of rat olfactory receptor I7. The constructs include an N-terminal Flag epitope tag (Flag:I7), enhanced green fluorescent protein (EGFP) fusion protein (EGFP:I7), and a C-terminal EGFP fusion (I7:EGFP). These receptor constructs were assayed in rat olfactory sensory neurons (OSNs) and in a heterologous system (HEK 293 cell line) for protein localization and functional expression. Functional expression of the tagged receptor proteins was tested by electroolfactogram (EOG) recordings in the infected rat olfactory epithelium, and by calcium imaging in single cells. Our results demonstrate that the I7:EGFP fusion protein and Flag:I7 are functionally expressed in OSNs while the EGFP:I7 fusion is not, probably due to inappropriate processing of the protein in the cells. These data suggest that a small epitope tag (Flag) at the N-terminus, or EGFP located at the C-terminus of the receptor, does not affect ligand binding or downstream signaling. In addition, both functional fusion proteins (Flag:I7 and I7:EGFP) are properly targeted to the plasma membrane of HEK 293 cells. PMID:11748633

  19. Engineering Airway Epithelium

    PubMed Central

    Soleas, John P.; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium. PMID:22523471

  20. The development of the olfactory organs in newly hatched monotremes and neonate marsupials

    PubMed Central

    Schneider, Nanette Yvette

    2011-01-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  1. The development of the olfactory organs in newly hatched monotremes and neonate marsupials.

    PubMed

    Schneider, Nanette Yvette

    2011-08-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  2. Monoclonal antibodies reveal cell-type-specific antigens in the sexually dimorphic olfactory system of Manduca sexta. II. Expression of antigens during postembryonic development.

    PubMed

    Hishinuma, A; Hockfield, S; McKay, R; Hildebrand, J G

    1988-01-01

    Two classes of monoclonal antibodies specific to the olfactory system of Manduca sexta have been isolated: the olfactory-specific antibody (OSA), which specifically recognizes many or all olfactory receptor cells (ORCs) in both males and females, and the male olfactory-specific antibody (MOSA), which stains male-specific receptor cells (principally or exclusively sex-pheromone receptors present only in antennae of males; Hishinuma et al., 1988). In the investigation reported here, we examined the expression of the antigens during postembryonic development in order to correlate the presence of particular antigens with the status of differentiation of the ORCs or with their acquisition of particular functions. As assessed immunocytochemically, the OSA recognizes certain epithelial cells in the antennal imaginal disk of the fifth-instar larva. Later, during the first 70 hr of adult development, when differentiative cell divisions are occurring in the antennal epithelium to generate ORCs and the other cells that make up olfactory sensilla, no cells are stained. Immediately after this period of mitoses, the OSA immunoreactivity reappears exclusively in the ORCs, which begin to elaborate axons as an early event in their differentiation. On immunoblots, the OSA recognizes specific sets of molecules (distinguished on the basis of their apparent molecular weights): 53,000 and 59,000 Da antigens in the disk epithelial cells in the last-instar larva; 53,000, 59,000, and 66,000 Da antigens in the ORCs from 15 to 60% of metamorphic adult development; and 42,000, 59,000, and 66,000 Da antigens in the ORCs from 60 to 100% of adult development. The MOSA also recognizes a subset of the epithelial cells in the antennal disks in male and female larvae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3339412

  3. Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium.

    PubMed

    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 (Ca(2+))-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca(2+), and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca(2+) 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

  4. 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

  5. Photoperiod Mediated Changes in Olfactory Bulb Neurogenesis and Olfactory Behavior in Male White-Footed Mice (Peromyscus leucopus)

    PubMed Central

    Weil, Zachary M.; Nelson, Randy J.

    2012-01-01

    Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus. PMID:22912730

  6. The Pig Olfactory Brain: A Primer.

    PubMed

    Brunjes, Peter C; Feldman, Sanford; Osterberg, Stephen K

    2016-06-01

    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

  7. 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

  8. Seasonal increase in olfactory receptor neurons of the Japanese toad, Bufo japonicus, is paralleled by an increase in olfactory sensitivity to isoamyl acetate.

    PubMed

    Nakazawa, Hideo; Ichikawa, Masumi; Nagai, Takatoshi

    2009-10-01

    Japanese toads (Bufo japonicus) migrate to and from breeding sites in the early spring, possibly guided by olfactory cues. We previously showed that the electrical activity of olfactory receptor neurons (ORNs) in the toads was enhanced in the breeding period. We undertook morphological and physiological studies of the olfactory epithelium to determine whether any cellular substrate of the epithelium underlies the enhanced electrical activity of ORNs. The ORNs of the toads were labeled by antiserum to olfactory marker protein (OMP), and the morphology of the labeled cells and their distribution in the epithelium were examined throughout the year. The OMP-positive cells, distributed mainly in the basal and intermediate layers of the epithelium, were most numerous in the early breeding period. Cell proliferation in the epithelium detected by 5-bromo-2'-deoxyuridine labeling was most elevated in this period. The electrical activity of ORNs was examined by recording the electroolfactogram (EOG) in the toads throughout the year. Statistical analysis showed a positive correlation between the density of OMP-positive cells in the epithelium and the amplitude of the EOG responses. A greater number of ORNs in the breeding period possibly aids the toads in migrating to their breeding sites. PMID:19643818

  9. Pattern of olfactory bulb innervation returns after recovery from reversible peripheral deafferentation.

    PubMed

    Cummings, D M; Emge, D K; Small, S L; Margolis, F L

    2000-06-01

    The olfactory epithelium (OE) is unusual in its ability to regenerate and reinnervate its target, the olfactory bulb (OB), after deafferentation. To address the question of whether olfactory receptor neuron (ORN) axons preserve their topographic organization when they reestablish synaptic contact with the OB, the authors examined the pattern of ORN axon reinnervation into the bulb of adult H-OMP-lacZ-6 transgenic mice during and after recovery from chemical deafferentation. In the H-OMP-lacZ-6 mouse strain, lacZ expression is limited to a subset of ORNs that are distributed bilaterally in the OE and project primarily to a few glomeruli in the ventromedial region of the OB. The OE was lesioned by intranasal irrigation with Triton X-100, and the distribution of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal)-stained cells was examined in the OE along with beta-galactosidase-immunoreactive (beta-gal-ir) axonal processes in the OB after short (1 week), intermediate (3 week), and long (6-7 weeks) recovery times. One week after the lesion, immunostaining for beta-gal and olfactory marker protein was virtually eliminated in the bulb. After 3 weeks of recovery, beta-gal-containing axons appeared to target many of the same locations innervated in bulbs of unlesioned mice. The region that received the highest density of axonal innervation in controls, however, contained only a few processes at that time. After 6-7 week recovery periods, the pattern of X-gal staining in the OE and beta-gal-ir axons in the OB closely resembled that of unlesioned mice. These results demonstrate that the topographic distribution of ORNs in the OE and the pattern of axon innervation in the OB can be reconstituted after chemical deafferentation. PMID:10813792

  10. Neuronal organization of olfactory bulb circuits

    PubMed Central

    Nagayama, Shin; Homma, Ryota; Imamura, Fumiaki

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit. PMID:25232305

  11. The loss of scents: do defects in olfactory sensory neuron development underlie human disease?

    PubMed

    Whitlock, Kathleen E

    2015-06-01

    The olfactory system is a fascinating and beguiling sensory system: olfactory sensory neurons detect odors underlying behaviors essential for mate choice, food selection, and escape from predators, among others. These sensory neurons are unique in that they have dendrites contacting the outside world, yet their first synapse lies in the central nervous system. The information entering the central nervous system is used to create odor memories that play a profound role in recognition of individuals, places, and appropriate foods. Here, the structure of the olfactory epithelium is given as an overview to discuss the origin of the olfactory placode, the plasticity of the olfactory sensory neurons, and finally the origins of the gonadotropin-releasing hormone neuroendocrine cells. For the purposes of this review, the development of the peripheral sensory system will be analyzed, incorporating recently published studies highlighting the potential novelties in development mechanisms. Specifically, an emerging model where the olfactory epithelium and olfactory bulb develop simultaneously from a continuous neurectoderm patterned at the end of gastrulation, and the multiple origins of the gonadotropin-releasing hormone neuroendocrine cells associated with the olfactory sensory system development will be presented. Advances in the understanding of the basic mechanisms underlying olfactory sensory system development allows for a more thorough understanding of the potential causes of human disease. PMID:26111003

  12. Nonoccupational environmental exposure to manganese is linked to deficits in peripheral and central olfactory function.

    PubMed

    Guarneros, Marco; Ortiz-Romo, Nahum; Alcaraz-Zubeldia, Mireya; Drucker-Colín, René; Hudson, Robyn

    2013-11-01

    Manganese is of growing concern as a toxic air pollutant. It is readily transported from the olfactory epithelium to the olfactory bulb, and unlike other metals, it is transported transynaptically to structures deep within the brain. However, little is known regarding the possible effect of nonoccupational exposure to manganese on olfactory function. Using the Sniffin' Sticks test battery, we compared the olfactory performance of subjects from a manganese mining district living <1 km from a manganese processing plant, with nonexposed subjects living 50 km from the closest source of exposure (N = 30/group). Groups were matched for age, sex, and schooling, and none had ever worked in mining-related activities. Concentrations of manganese in hair were measured as a biomarker of exposure; exposed subjects had significantly higher concentrations than nonexposed subjects. They were also significantly outperformed by the nonexposed subjects on all olfactory measures (threshold, discrimination, and identification), indicating adverse effects of manganese exposure on a range of olfactory functions, including those involving higher order cognitive processes. This contrasts with previous findings showing adverse peripheral but not central effects on olfactory function of big city air pollution, which mostly consists of toxicants known to affect the olfactory epithelium but with lower transynaptic transport capacity compared with manganese. We conclude that nonoccupational exposure to airborne manganese is associated with decrements in both peripheral and central olfactory function. PMID:24097266

  13. From the Cover: Odor maps in the olfactory cortex

    NASA Astrophysics Data System (ADS)

    Zou, Zhihua; Li, Fusheng; Buck, Linda B.

    2005-05-01

    In the olfactory system, environmental chemicals are deconstructed into neural signals and then reconstructed to form odor perceptions. Much has been learned about odor coding in the olfactory epithelium and bulb, but little is known about how odors are subsequently encoded in the cortex to yield diverse perceptions. Here, we report that the representation of odors by fixed glomeruli in the olfactory bulb is transformed in the cortex into highly distributed and multiplexed odor maps. In the mouse olfactory cortex, individual odorants are represented by subsets of sparsely distributed neurons. Different odorants elicit distinct, but partially overlapping, patterns that are strikingly similar among individuals. With increases in odorant concentration, the representations expand spatially and include additional cortical neurons. Structurally related odorants have highly related representations, suggesting an underlying logic to the mapping of odor identities in the cortex. odorant receptor | smell

  14. Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report.

    PubMed

    Leon-Soriano, Elena; Alfonso, Carolina; Yebenes, Laura; Garcia-Polo, Julio; Lassaletta, Luis; Gavilan, Javier

    2016-01-01

    BACKGROUND Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant head and neck cancer thought to originate from the olfactory epithelium. It typically invades contiguous structures at presentation. We report a very rare case of multifocal and ectopic ONB. CASE REPORT A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses. Histopathological diagnosis after endoscopic resection established bilateral olfactory neuroblastoma of the ethmoid sinuses. The patient received postoperative radiotherapy. He remains free of disease 4 years after treatment. CONCLUSIONS To the best of our knowledge this is the second documented case of multifocal ectopic olfactory neuroblastoma. Clinicians should consider ONB in the differential diagnosis of bilateral synchronous nasal and paranasal masses to avoid delayed diagnosis. Endoscopic resection of ONB could be an option in selected cases. PMID:27097989

  15. Expression patterns of nicotinic subunits α2, α7, α8, and β1 affect the kinetics and pharmacology of ACh-induced currents in adult bee olfactory neuropiles.

    PubMed

    Dupuis, Julien Pierre; Gauthier, Monique; Raymond-Delpech, Valérie

    2011-10-01

    Acetylcholine (ACh) is the main excitatory neurotransmitter of the insect brain, where nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission. In the honeybee Apis mellifera, nAChRs are expressed in diverse structures including the primary olfactory centers of the brain, the antennal lobes (ALs) and the mushroom bodies (MBs), where they participate in olfactory information processing. To understand the nature and properties of the nAChRs involved in these processes, we performed a pharmacological and molecular characterization of nAChRs on cultured Kenyon cells of the MBs, using whole cell patch-clamp recordings combined with single-cell RT-PCR. In all cells, applications of ACh as well as nicotinic agonists such as nicotine and imidacloprid induced inward currents with fast desensitization. These currents were fully blocked by saturating doses of the antagonists α-bungarotoxin (α-BGT), dihydroxy-β-erythroidine (DHE), and methyllycaconitine (MLA) (MLA ≥ α-BGT ≥ DHE). Molecular analysis of ACh-responding cells revealed that of the 11 nicotinic receptor subunits encoded within the honeybee genome, α2, α8, and β1 subunits were expressed in adult Kenyon cells. Comparison with the expression pattern of adult AL cells revealed the supplementary presence of subunit α7, which could be responsible for the kinetic and pharmacological differences observed when comparing ACh-induced currents from AL and Kenyon cells. Together, our data demonstrate the existence of functional nAChRs on adult MB Kenyon cells that differ from nAChRs on AL cells in both their molecular composition and pharmacological properties, suggesting that changing receptor subsets could mediate different processing functions depending on the brain structure within the olfactory pathway. PMID:21734106

  16. Histochemical and ultrastructural analyses of the lubrication systems in the olfactory organs of soft-shelled turtle

    PubMed Central

    NAKAMUTA, Shoko; YOKOSUKA, Makoto; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; NAKAMUTA, Nobuaki

    2016-01-01

    In general, the nasal cavity of turtles is divided into two chambers: the upper chamber, lined with the olfactory epithelium containing ciliated olfactory receptor cells, and the lower chamber, lined with the vomeronasal epithelium containing microvillous receptor cells. In the nasal cavity of soft-shelled turtles, however, differences between the upper and lower chamber epithelia are unclear due to the presence of ciliated receptor cells in both epithelia. In the olfactory organ of vertebrates, the surface of sensory epithelium is covered with secretory products of associated glands and supporting cells, playing important roles in the olfaction by dissolving odorants and transporting them to the olfactory receptors. Here, the associated glands and supporting cells in the olfactory organ of soft-shelled turtles were analyzed histochemically and ultrastructurally. The upper chamber epithelium possessed associated glands, constituted by cells containing serous secretory granules; whereas, the lower chamber epithelium did not. In the upper chamber epithelium, secretory granules filled the supranuclear region of supporting cells, while most of the granules were distributed near the free border of supporting cells in the lower chamber epithelium. The secretory granules in the supporting cells of both epithelia were seromucous, but alcian blue stained them differently from each other. In addition, distinct expression of carbohydrates was suggested by the differences in lectin binding. These data indicate the quantitative and qualitative differences in the secretory properties between the upper and lower chamber epithelia, suggesting their distinct roles in the olfaction. PMID:26782135

  17. Histochemical and ultrastructural analyses of the lubrication systems in the olfactory organs of soft-shelled turtle.

    PubMed

    Nakamuta, Shoko; Yokosuka, Makoto; Taniguchi, Kazumi; Yamamoto, Yoshio; Nakamuta, Nobuaki

    2016-06-01

    In general, the nasal cavity of turtles is divided into two chambers: the upper chamber, lined with the olfactory epithelium containing ciliated olfactory receptor cells, and the lower chamber, lined with the vomeronasal epithelium containing microvillous receptor cells. In the nasal cavity of soft-shelled turtles, however, differences between the upper and lower chamber epithelia are unclear due to the presence of ciliated receptor cells in both epithelia. In the olfactory organ of vertebrates, the surface of sensory epithelium is covered with secretory products of associated glands and supporting cells, playing important roles in the olfaction by dissolving odorants and transporting them to the olfactory receptors. Here, the associated glands and supporting cells in the olfactory organ of soft-shelled turtles were analyzed histochemically and ultrastructurally. The upper chamber epithelium possessed associated glands, constituted by cells containing serous secretory granules; whereas, the lower chamber epithelium did not. In the upper chamber epithelium, secretory granules filled the supranuclear region of supporting cells, while most of the granules were distributed near the free border of supporting cells in the lower chamber epithelium. The secretory granules in the supporting cells of both epithelia were seromucous, but alcian blue stained them differently from each other. In addition, distinct expression of carbohydrates was suggested by the differences in lectin binding. These data indicate the quantitative and qualitative differences in the secretory properties between the upper and lower chamber epithelia, suggesting their distinct roles in the olfaction. PMID:26782135

  18. Nasal toxicity, carcinogenicity, and olfactory uptake of metals.

    PubMed

    Sunderman, F W

    2001-01-01

    Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved. PMID:11314863

  19. Nasal Administration of Cholera Toxin as a Mucosal Adjuvant Damages the Olfactory System in Mice

    PubMed Central

    Fukuyama, Yoshiko; Okada, Kazunari; Yamaguchi, Masahiro; Kiyono, Hiroshi; Mori, Kensaku; Yuki, Yoshikazu

    2015-01-01

    Cholera toxin (CT) induces severe diarrhea in humans but acts as an adjuvant to enhance immune responses to vaccines when administered orally. Nasally administered CT also acts as an adjuvant, but CT and CT derivatives, including the B subunit of CT (CTB), are taken up from the olfactory epithelium and transported to the olfactory bulbs and therefore may be toxic to the central nervous system. To assess the toxicity, we investigated whether nasally administered CT or CT derivatives impair the olfactory system. In mice, nasal administration of CT, but not CTB or a non-toxic CT derivative, reduced the expression of olfactory marker protein (OMP) in the olfactory epithelium and olfactory bulbs and impaired odor responses, as determined with behavioral tests and optical imaging. Thus, nasally administered CT, like orally administered CT, is toxic and damages the olfactory system in mice. However, CTB and a non-toxic CT derivative, do not damage the olfactory system. The optical imaging we used here will be useful for assessing the safety of nasal vaccines and adjuvants during their development for human use and CT can be used as a positive control in this test. PMID:26422280

  20. Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2

    PubMed Central

    Pifferi, Simone; Dibattista, Michele; Sagheddu, Claudia; Boccaccio, Anna; Al Qteishat, Ahmed; Ghirardi, Filippo; Tirindelli, Roberto; Menini, Anna

    2009-01-01

    Olfactory sensory neurons use a chloride-based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca2+ into the cilia. Ca2+ activates a Cl− current that produces an efflux of Cl− ions and amplifies the depolarization. The molecular identity of Ca2+-activated Cl− channels is still elusive, although some bestrophins have been shown to function as Ca2+-activated Cl− channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin-2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca2+-activated Cl− channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca2+-activated Cl− currents in wild-type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca2+-activated Cl− currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons. PMID:19622610

  1. The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo

    PubMed Central

    Hassenklöver, Thomas; Manzini, Ivan

    2014-01-01

    The olfactory system has the unusual capacity to generate new neurons throughout the lifetime of an organism. Olfactory stem cells in the basal portion of the olfactory epithelium continuously give rise to new sensory neurons that extend their axons into the olfactory bulb, where they face the challenge to integrate into existing circuitry. Because of this particular feature, the olfactory system represents a unique opportunity to monitor axonal wiring and guidance, and to investigate synapse formation. Here we describe a procedure for in vivo labeling of sensory neurons and subsequent visualization of axons in the olfactory system of larvae of the amphibian Xenopus laevis. To stain sensory neurons in the olfactory organ we adopt the electroporation technique. In vivo electroporation is an established technique for delivering fluorophore-coupled dextrans or other macromolecules into living cells. Stained sensory neurons and their axonal processes can then be monitored in the living animal either using confocal laser-scanning or multiphoton microscopy. By reducing the number of labeled cells to few or single cells per animal, single axons can be tracked into the olfactory bulb and their morphological changes can be monitored over weeks by conducting series of in vivo time lapse imaging experiments. While the described protocol exemplifies the labeling and monitoring of olfactory sensory neurons, it can also be adopted to other cell types within the olfactory and other systems. PMID:25406975

  2. ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.

    PubMed

    Jia, C; Cussen, A R; Hegg, C C

    2011-03-17

    Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium (OE); however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxal-phosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development. PMID:21187124

  3. ATP differentially upregulates growth factors FGF2 and TGFα in neonatal and adult mice: Effect on neuroproliferation

    PubMed Central

    Jia, Cuihong; Cussen, Amber R.; Hegg, Colleen Cosgrove

    2011-01-01

    Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium; however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development. PMID:21187124

  4. Cellular Basis for the Olfactory Response to Nicotine

    PubMed Central

    2010-01-01

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (RoseJ. E., et al. (1993) Pharmacol., Biochem. Behav.1 (3), 891−9008469698). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (MombaertsP. (1999) Annu. Rev. Neurosci.1, 487−50910202546), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (GomezG., et al. (2000) J. Neurosci. Res.1 (3), 737−74911104513), and rat olfactory neurons. Rat and human OSNs responded to S(−)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  5. Cellular basis for the olfactory response to nicotine.

    PubMed

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  6. Expression of CD36 by Olfactory Receptor Cells and Its Abundance on the Epithelial Surface in Mice

    PubMed Central

    Tsuzuki, Satoshi; Matsumura, Shigenobu; Inoue, Kazuo; Iwanaga, Toshihiko; Masuda, Daisaku; Yamashita, Shizuya; Fushiki, Tohru

    2015-01-01

    CD36 is a transmembrane protein that is involved in the recognition of certain amphiphilic molecules such as polar lipids in various tissues and body fluids. So far, CD36 homologues in insects have been demonstrated to be present on the surface of olfactory dendrites and to participate in the perception of exogenous compounds. However, little is known about the relationship between CD36 and mammalian olfaction. Indeed, the detection of only CD36 mRNA in the mouse olfactory epithelium has been reported to date. In the present study, to provide potential pieces of evidence for the involvement of CD36 in mammalian olfactory perception, we extensively investigated the localisation of this protein in the mouse olfactory mucosa. In situ hybridisation analysis using antisense oligonucleotides to CD36 mRNA detected aggregated signals within the deeper epithelial layer of olfactory mucosa. The mRNA signals were also detected consistently in the superficial layer of the olfactory epithelium, which is occupied by supporting cells. Immunostaining with an anti-CD36 polyclonal antibody revealed that CD36 localises in the somata and dendrites of distinct olfactory receptor cells and that it occurs abundantly on the olfactory epithelial surface. However, immunoreactive CD36 was rarely detectable in the nerve bundles running in the lamina propria of olfactory mucosa, the axons forming the olfactory nerve layer in the outermost layer of the bulb and axon terminals in the glomeruli. We also obtained electron microscopic evidence for the association of CD36 protein with olfactory cilia. Altogether, we suggest that CD36 plays a role in the mammalian olfaction. In addition, signals for CD36 protein were also detected on or around the microvilli of olfactory supporting cells and the cilia of nasal respiratory epithelium, suggesting a role for this protein other than olfaction in the nasal cavity. PMID:26186589

  7. Histological and lectin histochemical studies on the olfactory and respiratory mucosae of the sheep.

    PubMed

    Ibrahim, Dalia; Nakamuta, Nobuaki; Taniguchi, Kazumi; Yamamoto, Yoshio; Taniguchi, Kazuyuki

    2014-03-01

    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

  8. Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion.

    PubMed

    He, Xu; Deng, Feng-Jun; Ge, Jin-Wen; Yan, Xiao-Xin; Pan, Ai-Hua; Li, Zhi-Yuan

    2015-09-01

    The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total saponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of doublecortin (DCX)(+) neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX(+) neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX(+) cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein. PMID:26604906

  9. The influence of nasal airflow on respiratory and olfactory epithelial distribution in felids.

    PubMed

    Pang, Benison; Yee, Karen K; Lischka, Fritz W; Rawson, Nancy E; Haskins, Mark E; Wysocki, Charles J; Craven, Brent A; Van Valkenburgh, Blaire

    2016-06-15

    The surface area of the maxilloturbinals and fronto-ethmoturbinals is commonly used as an osteological proxy for the respiratory and the olfactory epithelium, respectively. However, this assumption does not fully account for animals with short snouts in which these two turbinal structures significantly overlap, potentially placing fronto-ethmoturbinals in the path of respiratory airflow. In these species, it is possible that anterior fronto-ethmoturbinals are covered with non-sensory (respiratory) epithelium instead of olfactory epithelium. In this study, we analyzed the distribution of olfactory and non-sensory, respiratory epithelia on the turbinals of two domestic cats (Felis catus) and a bobcat (Lynx rufus). We also conducted a computational fluid dynamics simulation of nasal airflow in the bobcat to explore the relationship between epithelial distribution and airflow patterns. The results showed that a substantial amount of respiratory airflow passes over the anterior fronto-ethmoturbinals, and that contrary to what has been observed in caniform carnivorans, much of the anterior ethmoturbinals are covered by non-sensory epithelium. This confirms that in short-snouted felids, portions of the fronto-ethmoturbinals have been recruited for respiration, and that estimates of olfactory epithelial coverage based purely on fronto-ethmoturbinal surface area will be exaggerated. The correlation between the shape of the anterior fronto-ethmoturbinals and the direction of respiratory airflow suggests that in short-snouted species, CT data alone are useful in assessing airflow patterns and epithelium distribution on the turbinals. PMID:27045093

  10. Adenovirus-mediated WGA gene delivery for transsynaptic labeling of mouse olfactory pathways.

    PubMed

    Kinoshita, Nanako; Mizuno, Takeo; Yoshihara, Yoshihiro

    2002-03-01

    Detailed knowledge of neuronal connectivity patterns is indispensable for studies of various aspects of brain functions. We previously established a genetic strategy for visualization of multisynaptic neural pathways by expressing wheat germ agglutinin (WGA) transgene under the control of neuron type-specific promoter elements in transgenic mice and Drosophila. In this paper, we have developed a WGA-expressing recombinant adenoviral vector system and applied it for analysis of the olfactory system. When the WGA-expressing adenovirus was infused into a mouse nostril, various types of cells throughout the olfactory epithelium were infected and expressed WGA protein robustly. WGA transgene products in the olfactory sensory neurons were anterogradely transported along their axons to the olfactory bulb and transsynaptically transferred in glomeruli to dendrites of the second-order neurons, mitral and tufted cells. WGA protein was further conveyed via the lateral olfactory tract to the olfactory cortical areas including the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral entorhinal cortex. In addition, transsynaptic retrograde labeling was observed in cholinergic neurons in the horizontal limb of diagonal band, serotonergic neurons in the median raphe nucleus, and noradrenergic neurons in the locus coeruleus, all of which project centrifugal fibers to the olfactory bulb. Thus, the WGA-expressing adenovirus is a useful and powerful tool for tracing neural pathways and could be used in animals that are not amenable to the transgenic technology. PMID:11923184

  11. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population. PMID:26441369

  12. A Screen for Genes Expressed in the Olfactory Organs of Drosophila melanogaster Identifies Genes Involved in Olfactory Behaviour

    PubMed Central

    Tunstall, Narelle E.; Herr, Anabel; de Bruyne, Marien; Warr, Coral G.

    2012-01-01

    Background For insects the sense of smell and associated olfactory-driven behaviours are essential for survival. Insects detect odorants with families of olfactory receptor proteins that are very different to those of mammals, and there are likely to be other unique genes and genetic pathways involved in the function and development of the insect olfactory system. Methodology/Principal Findings We have performed a genetic screen of a set of 505 Drosophila melanogaster gene trap insertion lines to identify novel genes expressed in the adult olfactory organs. We identified 16 lines with expression in the olfactory organs, many of which exhibited expression of the trapped genes in olfactory receptor neurons. Phenotypic analysis showed that six of the lines have decreased olfactory responses in a behavioural assay, and for one of these we showed that precise excision of the P element reverts the phenotype to wild type, confirming a role for the trapped gene in olfaction. To confirm the identity of the genes trapped in the lines we performed molecular analysis of some of the insertion sites. While for many lines the reported insertion sites were correct, we also demonstrated that for a number of lines the reported location of the element was incorrect, and in three lines there were in fact two pGT element insertions. Conclusions/Significance We identified 16 new genes expressed in the Drosophila olfactory organs, the majority in neurons, and for several of the gene trap lines demonstrated a defect in olfactory-driven behaviour. Further characterisation of these genes and their roles in olfactory system function and development will increase our understanding of how the insect olfactory system has evolved to perform the same essential function to that of mammals, but using very different molecular genetic mechanisms. PMID:22530061

  13. Electrophysiological evidence for the broad distribution of specific odorant receptor molecules across the olfactory organ of the channel catfish.

    PubMed

    Chang, Q; Caprio, J

    1996-10-01

    To determine if there is a spatial segregation of responsiveness to odorants within the olfactory epithelium, microelectrode recordings were obtained from small populations of olfactory receptor neurons located across different lamellar sensory regions of the olfactory organ of the channel catfish, lctalurus punctatus. Stimuli included L-alanine, L-methionine, L-arginine hydrochloride, L-glutamic acid, ATP and a mixture of bile salts-odorants previously reported to stimulate independent receptor sites in aquatic species. The peak integrated olfactory receptor responses at each recording site were standardized to the response to L-alanine. The relative stimulatory effectiveness of the stimuli was preserved across the 10 olfactory lamellae recording sites. These data support previous molecular biological results of a broad distribution of receptor neurons that express specific receptor genes across the olfactory organ of the channel catfish. PMID:8902281

  14. Analyzing responses of mouse olfactory sensory neurons using the air-phase electroolfactogram recording.

    PubMed

    Cygnar, Katherine D; Stephan, Aaron B; Zhao, Haiqing

    2010-01-01

    Animals depend on olfaction for many critical behaviors, such as finding food sources, avoiding predators, and identifying conspecifics for mating and other social interactions. The electroolfactogram (EOG) recording is an informative, easy to conduct, and reliable method to assay olfactory function at the level of the olfactory epithelium. Since the 1956 description of the EOG by Ottoson in frogs, the EOG recording has been applied in many vertebrates including salamanders, rabbits, rats, mice, and humans (reviewed by Scott and Scott-Johnson, 2002, ref. 2). The recent advances in genetic modification in mice have rekindled interest in recording the EOG for physiological characterization of olfactory function in knock-out and knock-in mice. EOG recordings have been successfully applied to demonstrate the central role of olfactory signal transduction components, and more recently to characterize the contribution of certain regulatory mechanisms to OSN responses. Odorant detection occurs at the surface of the olfactory epithelium on the cilia of OSNs, where a signal transduction cascade leads to opening of ion channels, generating a current that flows into the cilia and depolarizes the membrane. The EOG is the negative potential recorded extracellularly at the surface of the olfactory epithelium upon odorant stimulation, resulting from a summation of the potential changes caused by individual responsive OSNs in the recording field. Comparison of the amplitude and kinetics of the EOG thus provide valuable information about how genetic modification and other experimental manipulations influence the molecular signaling underlying the OSN response to odor. Here we describe an air-phase EOG recording on a preparation of mouse olfactory turbinates. Briefly, after sacrificing the mouse, the olfactory turbinates are exposed by bisecting the head along the midline and removing the septum. The turbinate preparation is then placed in the recording setup, and a recording

  15. Analyzing Responses of Mouse Olfactory Sensory Neurons Using the Air-phase Electroolfactogram Recording

    PubMed Central

    Cygnar, Katherine D.; Stephan, Aaron B.; Zhao, Haiqing

    2010-01-01

    Animals depend on olfaction for many critical behaviors, such as finding food sources, avoiding predators, and identifying conspecifics for mating and other social interactions. The electroolfactogram (EOG) recording is an informative, easy to conduct, and reliable method to assay olfactory function at the level of the olfactory epithelium. Since the 1956 description of the EOG by Ottoson in frogs1, the EOG recording has been applied in many vertebrates including salamanders, rabbits, rats, mice, and humans (reviewed by Scott and Scott-Johnson, 2002, ref. 2). The recent advances in genetic modification in mice have rekindled interest in recording the EOG for physiological characterization of olfactory function in knock-out and knock-in mice. EOG recordings have been successfully applied to demonstrate the central role of olfactory signal transduction components3-8, and more recently to characterize the contribution of certain regulatory mechanisms to OSN responses9-12. Odorant detection occurs at the surface of the olfactory epithelium on the cilia of OSNs, where a signal transduction cascade leads to opening of ion channels, generating a current that flows into the cilia and depolarizes the membrane13. The EOG is the negative potential recorded extracellularly at the surface of the olfactory epithelium upon odorant stimulation, resulting from a summation of the potential changes caused by individual responsive OSNs in the recording field2. Comparison of the amplitude and kinetics of the EOG thus provide valuable information about how genetic modification and other experimental manipulations influence the molecular signaling underlying the OSN response to odor. Here we describe an air-phase EOG recording on a preparation of mouse olfactory turbinates. Briefly, after sacrificing the mouse, the olfactory turbinates are exposed by bisecting the head along the midline and removing the septum. The turbinate preparation is then placed in the recording setup, and a

  16. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception.

    PubMed

    Watanabe, Satoshi; Takanashi, Fumihito; Ishida, Kohei; Kobayashi, Suguru; Kitamura, Yoshiichiro; Hamasaki, Yuuta; Saito, Minoru

    2015-01-01

    Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID:26360020

  17. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception

    PubMed Central

    Kobayashi, Suguru; Kitamura, Yoshiichiro; Hamasaki, Yuuta; Saito, Minoru

    2015-01-01

    Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID:26360020

  18. Ionotropic Crustacean Olfactory Receptors

    PubMed Central

    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. PMID:23573266

  19. 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. PMID:23573266

  20. Application of the European Test of Olfactory Capabilities in patients with olfactory impairment.

    PubMed

    Joussain, P; Bessy, M; Faure, F; Bellil, D; Landis, B N; Hugentobler, M; Tuorila, H; Mustonen, S; Vento, S I; Delphin-Combe, F; Krolak-Salmon, P; Rouby, C; Bensafi, M

    2016-02-01

    A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings. PMID:25711735

  1. Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report

    PubMed Central

    Leon-Soriano, Elena; Alfonso, Carolina; Yebenes, Laura; Garcia-Polo, Julio; Lassaletta, Luis; Gavilan, Javier

    2016-01-01

    Patient: Male, 41 Final Diagnosis: Olfactory neuroblastoma Symptoms: Left nasal obstruction • occasional left epistaxis • headache Medication: None Clinical Procedure: Nasal endoscopic examination • neck palpation • CT • bilateral endoscopic resection • MRI • PET-CT • postoperative radiotherapy Specialty: Otolaryngology Objective: Unusual clinical course Background: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant head and neck cancer thought to originate from the olfactory epithelium. It typically invades contiguous structures at presentation. We report a very rare case of multifocal and ectopic ONB. Case Report: A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses. Histopathological diagnosis after endoscopic resection established bilateral olfactory neuroblastoma of the ethmoid sinuses. The patient received postoperative radiotherapy. He remains free of disease 4 years after treatment. Conclusions: To the best of our knowledge this is the second documented case of multifocal ectopic olfactory neuroblastoma. Clinicians should consider ONB in the differential diagnosis of bilateral synchronous nasal and paranasal masses to avoid delayed diagnosis. Endoscopic resection of ONB could be an option in selected cases. PMID:27097989

  2. 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

  3. Neurotrophins are not required for normal embryonic development of olfactory neurons.

    PubMed

    Nef, S; Lush, M E; Shipman, T E; Parada, L F

    2001-06-01

    Neurons of the vertebrate olfactory epithelium (OE) regenerate continuously throughout life. The capacity of these neurons to regenerate and make new and precise synaptic connections in the olfactory bulb provides a useful model to study factors that may control or mediate neuronal regeneration. Expression and in vitro studies have suggested potential roles for the neurotrophins in the olfactory system. To directly examine whether neurotrophins are required for olfactory neuron development, we characterized in vivo the role of the neurotrophins in the primary olfactory system. For this, we generated mutant mice for TrkA, TrkB, TrkC, and also for BDNF and NT3 together with P2-IRES-tau-LacZ trangenic mice. Histochemical staining for beta-galactosidase at birth allowed in vivo analysis of the P2 subpopulation of olfactory neurons as well as their projections to the olfactory bulb. Our data indicate that Trk signaling is not required for normal embryonic development of the olfactory system. PMID:11356021

  4. Functional Rehabilitation of Cadmium-Induced Neurotoxicity Despite Persistent Peripheral Pathophysiology in the Olfactory System

    PubMed Central

    Czarnecki, Lindsey A.; Moberly, Andrew H.; Turkel, Daniel J.; Rubinstein, Tom; Pottackal, Joseph; Rosenthal, Michelle C.; McCandlish, Elizabeth F. K.; Buckley, Brian; McGann, John P.

    2012-01-01

    Intranasal exposure to the heavy metal cadmium has been linked to olfactory dysfunction and neurotoxicity. Here, we combine optical imaging of in vivo neurophysiology, genetically defined anatomical tract tracing, mass spectrometry, and behavioral psychophysical methods to evaluate the persistent harmful effects of acute intranasal exposure to cadmium in a mouse model and to investigate the functional consequences of sensory rehabilitation training. We find that an acute intranasal instillation of cadmium chloride leads to an accumulation of cadmium in the brain's olfactory bulb that persists for at least 4 weeks. This is accompanied by persistent severe pathophysiology of the olfactory nerve, a gradual reduction in axonal projections from the olfactory epithelium, and complete impairment on an olfactory detection task. Remarkably, 2 weeks of odorant-guided operant conditioning training proved sufficient to restore olfactory detection performance to control levels in cadmium-exposed mice. Optical imaging from rehabilitated mice showed that this training did not cause any detectable restoration of olfactory nerve function, suggesting that the recovery of function was mediated by central neuroplasticity in which the brain learned to interpret the degraded sensory input. These data demonstrate that sensory learning can mask even severe damage from neurotoxicants and suggest that explicit sensory training may be useful in rehabilitation of olfactory dysfunction. PMID:22287023

  5. Ultrastructural and histochemical properties of the olfactory system in the japanese jungle crow, Corvus macrorhynchos.

    PubMed

    Kondoh, Daisuke; Nashimoto, Mai; Kanayama, Shunsaku; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2011-08-01

    Although it has been commonly believed that birds are more dependent on the vision and audition than the olfaction, recent studies indicate that the olfaction of birds is related to the reproductive, homing, and predatory behaviors. In an attempt to reveal the dependence on the olfactory system in crows, we examined the olfactory system of the Japanese jungle crow (Corvus macrorhynchos) by histological, ultrastructural, and lectin histochemical methods. The olfactory epithelium (OE) of the crow occupied remarkably a small area of the nasal cavity (NC) and had the histological and ultrastructural features like other birds. The olfactory bulb (OB) of the crow was remarkably small and did not possess the olfactory ventricle. The left and right halves of the OB were fused in many cases. In the lectin histochemistry, soybean agglutinin (SBA) and Vicia villosa agglutinin (VVA) stained a small number of the receptor cells (RCs) in the OE and the olfactory nerve layer (ONL) and glomerular layer (GL) on the dorsocaudal region of the OB. Phaseolus vulgaris agglutinin-E (PHA-E) stained several RCs in the OE and the ONL and GL on the ventral region of the OB. These results suggest that 1) the crow has less-developed olfactory system than other birds, and 2) the dedicated olfactory receptor cells project their axons to the specific regions of the OB in the crow. PMID:21478653

  6. Effects of Odor Stimulation on Antidromic Spikes in Olfactory Sensory Neurons

    PubMed Central

    Scott, John W.; Sherrill, Lisa

    2008-01-01

    Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very

  7. Effects of odor stimulation on antidromic spikes in olfactory sensory neurons.

    PubMed

    Scott, John W; Sherrill, Lisa

    2008-12-01

    Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very

  8. 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…

  9. Changes in Olfactory Receptor Expression Are Correlated With Odor Exposure During Early Development in the zebrafish (Danio rerio).

    PubMed

    Calfún, Cristian; Domínguez, Calixto; Pérez-Acle, Tomás; Whitlock, Kathleen E

    2016-05-01

    We have previously shown that exposure to phenyl ethyl alcohol (PEA) causes an increase in the expression of the transcription factor otx2 in the olfactory epithelium (OE) of juvenile zebrafish, and this change is correlated with the formation of an odor memory of PEA. Here, we show that the changes in otx2 expression are specific to βPEA: exposure to αPEA did not affect otx2 expression. We identified 34 olfactory receptors (ORs) representing 16 families on 4 different chromosomes as candidates for direct regulation of OR expression via Otx2. Subsequent in silico analysis uncovered Hnf3b binding sites closely associated with Otx2 binding sites in the regions flanking the ORs. Analysis by quantitative polymerase chain reaction and RNA-seq of OR expression in developing zebrafish exposed to different isoforms of PEA showed that a subset of ORs containing both Otx2/Hnf3b binding sites were downregulated only in βPEA-exposed juveniles and this change persisted through adult life. Localization of OR expression by in situ hybridization indicates the downregulation occurs at the level of RNA and not the number of cells expressing a given receptor. Finally, analysis of immediate early gene expression in the OE did not reveal changes in c-fos expression in response to either αPEA or βPEA. PMID:26892307

  10. Prenatal Stress Inhibits Hippocampal Neurogenesis but Spares Olfactory Bulb Neurogenesis

    PubMed Central

    Belnoue, Laure; Grosjean, Noelle; Ladevèze, Elodie

    2013-01-01

    The dentate gyrus (DG) and the olfactory bulb (OB) are two regions of the adult brain in which new neurons are integrated daily in the existing networks. It is clearly established that these newborn neurons are implicated in specific functions sustained by these regions and that different factors can influence neurogenesis in both structures. Among these, life events, particularly occurring during early life, were shown to profoundly affect adult hippocampal neurogenesis and its associated functions like spatial learning, but data regarding their impact on adult bulbar neurogenesis are lacking. We hypothesized that prenatal stress could interfere with the development of the olfactory system, which takes place during the prenatal period, leading to alterations in adult bulbar neurogenesis and in olfactory capacities. To test this hypothesis we exposed pregnant C57Bl/6J mice to gestational restraint stress and evaluated behavioral and anatomic consequences in adult male offspring. We report that prenatal stress has no impact on adult bulbar neurogenesis, and does not alter olfactory functions in adult male mice. However, it decreases cell proliferation and neurogenesis in the DG of the hippocampus, thus confirming previous reports on rats. Altogether our data support a selective and cross-species long-term impact of prenatal stress on neurogenesis. PMID:24009723

  11. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  12. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  13. Evidence for a Notch1-mediated transition during olfactory ensheathing cell development.

    PubMed

    Miller, Sophie R; Perera, Surangi N; Benito, Cristina; Stott, Simon R W; Baker, Clare V H

    2016-09-01

    Olfactory ensheathing cells (OECs) are a unique glial population found in both the peripheral and central nervous system: they ensheath bundles of unmyelinated olfactory axons from their peripheral origin in the olfactory epithelium to their central synaptic targets in the glomerular layer of the olfactory bulb. Like all other peripheral glia (Schwann cells, satellite glia, enteric glia), OECs are derived from the embryonic neural crest. However, in contrast to Schwann cells, whose development has been extensively characterised, relatively little is known about their normal development in vivo. In the Schwann cell lineage, the transition from multipotent Schwann cell precursor to immature Schwann cell is promoted by canonical Notch signalling. Here, in situ hybridisation and immunohistochemistry data from chicken, mouse and human embryos are presented that suggest a canonical Notch-mediated transition also occurs during OEC development. PMID:27271278

  14. Olfactory transduction in ciliated receptor neurons of the Cabinza grunt, Isacia conceptionis (Teleostei: Haemulidae).

    PubMed

    Schmachtenberg, Oliver; Bacigalupo, Juan

    2004-12-01

    The ciliated receptor neurons of fish olfactory organs are thought to transduce amino acids through a cAMP-dependent transduction pathway, but direct physiological evidence for this hypothesis remains scarce and is confined to catfish and trout. We investigated olfactory transduction in a marine fish, the Cabinza grunt Isacia conceptionis (Perciformes, Teleostei). The olfactory epithelium was characterized using light and electron microscopy, and isolated ciliated receptor neurons were recorded with the perforated patch-clamp technique. Cells were stimulated with puffer pipettes containing amino acid odourants, IBMX plus forskolin or 8 bromo-cAMP. All three stimuli triggered transient inward currents at a holding potential of -70 mV and responses with outward-rectifying current-voltage relationships. The characteristics of the transduction currents induced by each stimulus were similar across cells and indistinguishable within the same cell, supporting the hypothesis of a cAMP pathway mediating transduction of amino acids in ciliated olfactory receptor neurons. PMID:15610170

  15. Smoking-associated squamous metaplasia in olfactory mucosa of patients with chronic rhinosinusitis.

    PubMed

    Yee, Karen K; Pribitkin, Edmund A; Cowart, Beverly J; Vainius, Aldona A; Klock, Christopher T; Rosen, David; Hahn, Chang-Gyu; Rawson, Nancy E

    2009-08-01

    Few studies have examined the induction of squamous metaplasia in human olfactory nasal tissue caused by tobacco use and the implications it may have for olfaction, particularly when there are pre-existing insults, such as chronic rhinosinusitis (CRS). Quantitative histopathological analyses were performed on Alcian blue- and H&E-stained sections of nasal biopsies taken from the upper aspect of the middle turbinate of CRS patients. Chronic rhinosinusitis patients who were current smokers had a predominance of squamous metaplasia in the olfactory sensory epithelium, whereas CRS patients who were nonsmokers and were not exposed to secondhand cigarette smoke had a prevalence of goblet cell hyperplasia. In spite of this difference, the groups did not differ significantly in olfactory threshold sensitivity. The impact of primary cigarette smoke on olfaction and a possible role of squamous metaplasia in preserving olfactory neurogenesis are discussed. PMID:19487255

  16. Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo

    PubMed Central

    Cao, Luxiang; Schrank, Benjamin R.; Rodriguez, Steve; Benz, Eric G.; Moulia, Thomas W.; Rickenbacher, Gregory T.; Gomez, Alexis C.; Levites, Yona; Edwards, Sarah R.; Golde, Todd E.; Hyman, Bradley T.; Barnea, Gilad; Albers, Mark W.

    2012-01-01

    The Aβ peptide aggregates into amyloid plaques at presymptomatic stages of Alzheimer's disease, but the temporal relationship between plaque formation and neuronal dysfunction is poorly understood. Here, we demonstrate that the connectivity of the peripheral olfactory neural circuit is perturbed in mice overexpressing human APPsw (Swedish mutation) prior to the onset of plaques. Expression of hAPPsw exclusively in olfactory sensory neurons (OSNs) also perturbs connectivity with associated reductions in odor-evoked gene expression and olfactory acuity. By contrast, OSN axons project correctly in mice overexpressing wild type human APP throughout the brain and in mice overexpressing human APPmv, a missense mutation that reduces Aβ production, exclusively in OSNs. Furthermore, expression of Aβ40 or Aβ42 solely in the olfactory epithelium disrupts OSN axon targeting. Our data indicate that altering the structural connectivity and function of highly plastic neural circuits is one of the pleiotropic actions of soluble human Aβ. PMID:22910355

  17. Existence of Gαi2-expressing axon terminals in the goat main olfactory bulb.

    PubMed

    Ohara, Hiromi; Okamura, Hiroaki; Ichikawa, Masumi; Mori, Yuji; Hagino-Yamagishi, Kimiko

    2013-01-31

    In rodents, Gα(i2)-expressing sensory neurons (SNs) that co-express vomeronasal receptor type 1 (V1R) are specifically found in the vomeronasal organ (VNO) and project their axons to the accessory olfactory bulb (AOB). In goats, however, Gα(i2)/V1R-expressing SNs exist in both the VNO and the olfactory epithelium. Thus, we examined whether the Gα(i2)-expressing axons functionally project to the main olfactory bulb (MOB). We analyzed the expression of Gα(i2) in the olfactory bulb and found small Gα(i2)-immunoreactive clusters in the MOB. The Gα(i2)-immunoreactive axons in these clusters made synaptic contacts with second-order neurons in the MOB. These results suggest that some Gα(i2)-expressing SNs functionally project their axons to the MOB in goats. PMID:22878538

  18. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    PubMed Central

    Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2013-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. PMID:19440736

  19. Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing.

    PubMed

    Oettl, Lars-Lennart; Ravi, Namasivayam; Schneider, Miriam; Scheller, Max F; Schneider, Peggy; Mitre, Mariela; da Silva Gouveia, Miriam; Froemke, Robert C; Chao, Moses V; Young, W Scott; Meyer-Lindenberg, Andreas; Grinevich, Valery; Shusterman, Roman; Kelsch, Wolfgang

    2016-05-01

    Oxytocin promotes social interactions and recognition of conspecifics that rely on olfaction in most species. The circuit mechanisms through which oxytocin modifies olfactory processing are incompletely understood. Here, we observed that optogenetically induced oxytocin release enhanced olfactory exploration and same-sex recognition of adult rats. Consistent with oxytocin's function in the anterior olfactory cortex, particularly in social cue processing, region-selective receptor deletion impaired social recognition but left odor discrimination and recognition intact outside a social context. Oxytocin transiently increased the drive of the anterior olfactory cortex projecting to olfactory bulb interneurons. Cortical top-down recruitment of interneurons dynamically enhanced the inhibitory input to olfactory bulb projection neurons and increased the signal-to-noise of their output. In summary, oxytocin generates states for optimized information extraction in an early cortical top-down network that is required for social interactions with potential implications for sensory processing deficits in autism spectrum disorders. PMID:27112498

  20. Role of a ubiquitously expressed receptor in the vertebrate olfactory system.

    PubMed

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

    2013-09-18

    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

  1. Axon fasciculation in the developing olfactory nerve

    PubMed Central

    2010-01-01

    Olfactory sensory neuron (OSN) axons exit the olfactory epithelium (OE) and extend toward the olfactory bulb (OB) where they coalesce into glomeruli. Each OSN expresses only 1 of approximately 1,200 odor receptors (ORs). OSNs expressing the same OR are distributed in restricted zones of the OE. However, within a zone, the OSNs expressing a specific OR are not contiguous - distribution appears stochastic. Upon reaching the OB the OSN axons expressing the same OR reproducibly coalesce into two to three glomeruli. While ORs appear necessary for appropriate convergence of axons, a variety of adhesion associated molecules and activity-dependent mechanisms are also implicated. Recent data suggest pre-target OSN axon sorting may influence glomerular convergence. Here, using regional and OR-specific markers, we addressed the spatio-temporal properties associated with the onset of homotypic fasciculation in embryonic mice and assessed the degree to which subpopulations of axons remain segregated as they extend toward the nascent OB. We show that immediately upon crossing the basal lamina, axons uniformly turn sharply, usually at an approximately 90° angle toward the OB. Molecularly defined subpopulations of axons show evidence of spatial segregation within the nascent nerve by embryonic day 12, within 48 hours of the first OSN axons crossing the basal lamina, but at least 72 hours before synapse formation in the developing OB. Homotypic fasciculation of OSN axons expressing the same OR appears to be a hierarchical process. While regional segregation occurs in the mesenchyme, the final convergence of OR-specific subpopulations does not occur until the axons reach the inner nerve layer of the OB. PMID:20723208

  2. The Mouse Olfactory Peduncle

    PubMed Central

    Brunjes, Peter C; Kay, Rachel B; Arrivillaga, J. P

    2012-01-01

    The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention. The present work includes studies that provide an overview of the region in the mouse. An analysis of cell soma size in pars principalis (pP) of the anterior olfactory nucleus (AON) revealed considerable differences in tissue organization between mice and rats. An unbiased stereological study of neuron number in the cell-dense regions of pars externa (pE) and pP of the AON of 3, 12 and 24 month-old mice indicated that pE has about 16,500 cells in 0.043 mm3and pP about 58,300 cells in 0.307 mm3. Quantitative Golgi studies of pyramidal neurons in pP suggested that mouse neurons are similar though smaller to those of the rat. An immunohistochemical analysis demonstrated that all peduncular regions (pE, pP, the dorsal peduncular cortex, ventral tenia tecta, and anterior olfactory tubercle and piriform cortex) have cells that express either calbindin, calretinin, parvalbumin, somatostatin, vasoactive intestinal polypeptide, neuropeptide Y or cholecystokinin (antigens commonly co-expressed by subspecies of GABAergic neurons), though the relative numbers of each cell type differs between zones. Finally, an electron microscopic comparison of the organization of myelinated fibers in lateral olfactory tract in the anterior and posterior peduncle indicated that the region is less orderly in mice than in the rat. The results provide a caveat for investigators who generalize data between species as both similarities and differences between the laboratory mouse and rat were observed. PMID:21618219

  3. 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

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

    PubMed

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

    2011-01-01

    The olfactory system 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

  5. Properties and mechanisms of olfactory learning and memory

    PubMed Central

    Tong, Michelle T.; Peace, Shane T.; Cleland, Thomas A.

    2014-01-01

    Memories are dynamic physical phenomena with psychometric forms as well as characteristic timescales. Most of our understanding of the cellular mechanisms underlying the neurophysiology of memory, however, derives from one-trial learning paradigms that, while powerful, do not fully embody the gradual, representational, and statistical aspects of cumulative learning. The early olfactory system—particularly olfactory bulb—comprises a reasonably well-understood and experimentally accessible neuronal network with intrinsic plasticity that underlies both one-trial (adult aversive, neonatal) and cumulative (adult appetitive) odor learning. These olfactory circuits employ many of the same molecular and structural mechanisms of memory as, for example, hippocampal circuits following inhibitory avoidance conditioning, but the temporal sequences of post-conditioning molecular events are likely to differ owing to the need to incorporate new information from ongoing learning events into the evolving memory trace. Moreover, the shapes of acquired odor representations, and their gradual transformation over the course of cumulative learning, also can be directly measured, adding an additional representational dimension to the traditional metrics of memory strength and persistence. In this review, we describe some established molecular and structural mechanisms of memory with a focus on the timecourses of post-conditioning molecular processes. We describe the properties of odor learning intrinsic to the olfactory bulb and review the utility of the olfactory system of adult rodents as a memory system in which to study the cellular mechanisms of cumulative learning. PMID:25071492

  6. Ca2+-Activated Cl− Channels of the ClCa Family Express in the Cilia of a Subset of Rat Olfactory Sensory Neurons

    PubMed Central

    Gonzalez-Silva, Carolina; Vera, Jorge; Bono, María Rosa; González-Billault, Christian; Baxter, Brooke; Hansen, Anne; Lopez, Robert; Gibson, Emily A.

    2013-01-01

    The Ca2+-activated Cl− channel is considered a key constituent of odor transduction. Odorant binding to a specific receptor in the cilia of olfactory sensory neurons (OSNs) triggers a cAMP cascade that mediates the opening of a cationic cyclic nucleotide-gated channel (CNG), allowing Ca2+ influx. Ca2+ ions activate Cl− channels, generating a significant Cl− efflux, with a large contribution to the receptor potential. The Anoctamin 2 channel (ANO2) is a major constituent of the Cl− conductance, but its knock-out has no impairment of behavior and only slightly reduces field potential odorant responses of the olfactory epithelium. Likely, an additional Ca2+-activated Cl− channel of unknown molecular identity is also involved. In addition to ANO2, we detected two members of the ClCa family of Ca2+-activated Cl− channels in the rat olfactory epithelium, ClCa4l and ClCa2. These channels, also expressed in the central nervous system, may correspond to odorant transduction channels. Whole Sprague Dawley olfactory epithelium nested RT-PCR and single OSNs established that the mRNAs of both channels are expressed in OSNs. Real time RT-PCR and full length sequencing of amplified ClCa expressed in rat olfactory epithelium indicated that ClCa4l is the most abundant. Immunoblotting with an antibody recognizing both channels revealed immunoreactivity in the ciliary membrane. Immunochemistry of olfactory epithelium and OSNs confirmed their ciliary presence in a subset of olfactory sensory neurons. The evidence suggests that ClCa4l and ClCa2 might play a role in odorant transduction in rat olfactory cilia. PMID:23874937

  7. Neuropeptide receptors provide a signalling pathway for trigeminal modulation of olfactory transduction.

    PubMed

    Daiber, Philipp; Genovese, Federica; Schriever, Valentin A; Hummel, Thomas; Möhrlen, Frank; Frings, Stephan

    2013-02-01

    The mammalian olfactory epithelium contains olfactory receptor neurons and trigeminal sensory endings. The former mediate odor detection, the latter the detection of irritants. The two apparently parallel chemosensory systems are in reality interdependent in various well-documented ways. Psychophysical studies have shown that virtually all odorants can act as irritants, and that most irritants have an odor. Thus, the sensory perception of odorants and irritants is based on simultaneous input from the two systems. Moreover, functional interactions between the olfactory system and the trigeminal system exist on both peripheral and central levels. Here we examine the impact of trigeminal stimulation on the odor response of olfactory receptor neurons. Using an odorant with low trigeminal potency (phenylethyl alcohol) and a non-odorous irritant (CO(2) ), we have explored this interaction in psychophysical experiments with human subjects and in electroolfactogram (EOG) recordings from rats. We have demonstrated that simultaneous activation of the trigeminal system attenuates the perception of odor intensity and distorts the EOG response. On the molecular level, we have identified a route for this cross-modal interaction. The neuropeptide calcitonin-gene related peptide (CGRP), which is released from trigeminal sensory fibres upon irritant stimulation, inhibits the odor response of olfactory receptor neurons. CGRP receptors expressed by these neurons mediate this neuromodulatory effect. This study demonstrates a site of trigeminal-olfactory interaction in the periphery. It reveals a pathway for trigeminal impact on olfactory signal processing that influences odor perception. PMID:23205840

  8. Immunohistochemical and lectin histochemical studies on the developing olfactory organs of fetal camel.

    PubMed

    Ibrahim, Dalia; Taniguchi, Kazumi; Yamamoto, Yoshio; Taniguchi, Kazuyuki; Nakamuta, Nobuaki

    2015-07-01

    Little is known about the development of the olfactory organs of camel. In this study, prenatal development and neuronal differentiation of the vomeronasal organ (VNO) and the olfactory epithelium (OE) of the one-humped camel were studied by immunohistochemistry and lectin histochemistry. A neuronal marker, protein gene product (PGP) 9.5, but not a marker of fully differentiated olfactory receptor cells, olfactory marker protein, intensely labeled the olfactory receptor cells of the VNO and OE at 395 mm, 510 mm, and 530 mm fetal ages, indicating that the olfactory receptor cells are differentiated, but not fully matured both in the VNO and the OE. In 187 mm and 190 mm fetuses, PGP 9.5 yielded faint immunoreactive signals in the VNO, but not in the OE, although the presence of olfactory receptor cells were demonstrated in both tissues by intense WGA and LEL stainings. We conclude that the camel VNO and OE bear differentiated, but still immature receptor cells; in addition, the onset of neuronal differentiation seems to be somewhat earlier in the VNO than in the OE till half of the prenatal life. PMID:25950169

  9. Olfactory receptor response to CO2 in bullfrogs.

    PubMed

    Coates, E L; Ballam, G O

    1990-05-01

    In vivo electrophysiological recordings of olfactory receptor cells of the bullfrog (Rana catesbeiana) exhibit a receptor response to CO2 concentrations as low as 0.5%. The amplitude of the electroolfactogram (EOG) increased with an increase in the CO2 concentration delivered to the olfactory epithelium. Likewise, there was a significant increase in the decay time (time from 90 to 10% peak EOG amplitude) with an increase in CO2. The EOG rise time (time from 10 to 90% peak EOG amplitude) and the EOG response latency (time from beginning of CO2 pulse to beginning of EOG response) significantly decreased, whereas the plateau time (time from 90% rising phase to 90% falling phase of the peak EOG amplitude) was not significantly altered by an increase in CO2. These results indicate that low concentrations of CO2, below normal end expiratory CO2 concentrations, stimulate olfactory receptor cells. These results support our proposal that the ventilatory depression observed in response to upper airway CO2 in reptiles and amphibians is mediated by CO2-sensitive olfactory receptor cells. PMID:2110785

  10. 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

  11. Olfactory deficits cause anxiety-like behaviors in mice

    PubMed Central

    Glinka, Meredith E.; Samuels, Benjamin A.; Diodato, Assunta; Teillon, Jérémie; Mei, Dan Feng; Shykind, Benjamin M.; Hen, René; Fleischmann, Alexander

    2012-01-01

    Anxiety disorders are characterized by persistent fear in the absence of immediate threat and represent the most common psychiatric diseases, with an estimated 28% lifetime prevalence worldwide (R. C. Kessler et al., 2010). While symptoms of anxiety are typically evoked by sensory stimuli, it is unknown whether sensory deficits contribute to the development of anxiety disorders. Here we examine the effect of defined genetic mutations that compromise the function of the olfactory system on the development of anxiety-like behaviors in mice. We show that the functional inactivation of the main olfactory epithelium, but not the vomeronasal organ, causes elevated levels of anxiety. Anxiety-like behaviors are also observed in mice with a “monoclonal nose”, that are able to detect and discriminate odors but in which the patterns of odor-evoked neural activity are perturbed. In these mice, plasma corticosterone levels are elevated, suggesting that olfactory deficits can lead to chronic stress. These results demonstrate a central role for olfactory sensory cues in modulating anxiety in mice. PMID:22573694

  12. Olfactory deficits cause anxiety-like behaviors in mice.

    PubMed

    Glinka, Meredith E; Samuels, Benjamin A; Diodato, Assunta; Teillon, Jérémie; Feng Mei, Dan; Shykind, Benjamin M; Hen, René; Fleischmann, Alexander

    2012-05-01

    Anxiety disorders are characterized by persistent fear in the absence of immediate threat and represent the most common psychiatric diseases, with an estimated 28% lifetime prevalence worldwide (Kessler et al., 2010). While symptoms of anxiety are typically evoked by sensory stimuli, it is unknown whether sensory deficits contribute to the development of anxiety disorders. Here we examine the effect of defined genetic mutations that compromise the function of the olfactory system on the development of anxiety-like behaviors in mice. We show that the functional inactivation of the main olfactory epithelium, but not the vomeronasal organ, causes elevated levels of anxiety. Anxiety-like behaviors are also observed in mice with a monoclonal nose, that are able to detect and discriminate odors but in which the patterns of odor-evoked neural activity are perturbed. In these mice, plasma corticosterone levels are elevated, suggesting that olfactory deficits can lead to chronic stress. These results demonstrate a central role for olfactory sensory cues in modulating anxiety in mice. PMID:22573694

  13. Odor Memory Stability after Reinnervation of the Olfactory Bulb

    PubMed Central

    Blanco-Hernández, Eduardo; Valle-Leija, Pablo; Zomosa-Signoret, Viviana; Drucker-Colín, René; Vidaltamayo, Román

    2012-01-01

    The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain. PMID:23071557

  14. Short-Term Effects of Repeated Olfactory Administration of Homeopathic Sulphur or Pulsatilla on Electroencephalographic Alpha Power in Healthy Young Adults

    PubMed Central

    Bell, Iris R.; Brooks, Audrey J.; Howerter, Amy; Jackson, Nicholas; Schwartz, Gary E.

    2011-01-01

    Introduction Homeopathic pathogenetic trials usually rely on symptom self report measures. Adding objective biomarkers could enhance detection of subtle initial remedy effects. The present feasibility study examined electroencephalographic (EEG) effects of repeated olfactory administration of two polycrest remedies. Methods College student volunteers (ages 18–30, both sexes) from an introductory psychology course were screened for good health and relatively elevated Sulphur OR Pulsatilla symptom scores on the Homeopathic Constitutional Type Questionnaire. Subjects underwent a series of 3 once-weekly double-blind sessions during which they repeatedly sniffed the remedy matched to their CTQ type and solvent controls. Each remedy was given in a 6c, 12c, and 30c potency, one potency per week, in randomly assigned order. Solvent controls included both plain distilled water and a water-ethanol (95%) solution. All sniff test solutions were further diluted just prior to laboratory sessions (0.5 ml test solution in 150 ml distilled water). Within a session, remedies and control solvents were administered via 2-second sniffs (8 sniffs of each of 4 different succussion levels for the potency in randomized order). Primary outcome variable was relative EEG power (alpha 1 8–10 hertz; alpha 2 10–12 hertz) averaged over 19 electrode sites, including all succussions for a given potency. Results Mixed-effect models revealed significant main effects for remedy type (Sulphur>Pulsatilla) in both alpha bands, controlling for gender, baseline resting EEG alpha, and solvent control responses. Additional analyses showed significant non-linear interactions between dilution and time (weekly session) in alpha 2 for both remedies and alpha 1 for Sulphur. Conclusion EEG alpha offers an objective biomarker of remedy effects for future studies and potential method for distinguishing time-dependent effects of specific remedies and remedy potencies from one another. PMID:21962194

  15. Genetic architecture of olfactory behavior in Drosophila melanogaster: differences and similarities across development

    PubMed Central

    Lavagnino, N.J.; Arya, G.H.; Korovaichuk, A.; Fanara, J.J.

    2013-01-01

    In the holometabolous insect Drosophila melanogaster, genetic, physiological and anatomical aspects of olfaction are well known in the adult stage, while larval stages olfactory behavior has received some attention it has been less studied than its adult counterpart. Most of these studies focus on olfactory receptors (Or) genes that produce peripheral odor recognition. In this paper, through a loss-of-function screen using P-element inserted lines and also by means of expression analyses of larval olfaction candidate genes, we extended the uncovering of the genetic underpinnings of D. melanogaster larval olfactory behavior by demonstrating that larval olfactory behavior is, in addition to Or genes, orchestrated by numerous genes with diverse functions. Also, our results points out that the genetic architecture of olfactory behavior in D. melanogaster presents a dynamic and changing organization across environments and ontogeny. PMID:23563598

  16. Olfactory mucosa ultrastructure in the short-tailed shrews, Blarina brevicauda and Blarina carolinensis.

    PubMed

    Byrum, L J; Carson, K A; Rose, R K

    2001-12-01

    The olfactory mucosae of the northern short-tailed shrew, Blarina brevicauda, and the southern short-tailed shrew, Blarina carolinensis, were examined by light and electron microscopy. A well-developed olfactory epithelium was observed that included all of the cells necessary to provide for a sensitive olfactory system, suggesting that olfaction plays a major role in the behavior of these animals. There were no significant differences between the olfactory mucosae of these two species. The general features of the olfactory epithelium in these shrews were similar to those reported for several other macrosmatic mammals. A new type of supporting cell, called the light supporting cell, was observed in these shrews. The light supporting cell cytoplasm exhibited very little staining by light microscopy and had low electron density by transmission electron microscopy compared to that of the more common dark supporting cell. The light supporting cell had a convex apical surface with microvilli and lacked the large amounts of smooth endoplasmic reticulum (SER) typical of the apical cytoplasm of the dark supporting cell. In the lamina propria of the mucosa, the Bowman's glands consisted of two cell types, one with electron-lucent, alcian blue-positive granules, and the other with electron-dense PAS-positive granules. The cell with electron-lucent granules contained large amounts of SER and small clumps of rough ER. The cells with electron-dense granules had large amounts of RER and little SER. PMID:12221510

  17. Acetylcholine and Olfactory Perceptual Learning

    PubMed Central

    Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

    2007-01-01

    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 cortex. These changes include enhanced representation of the molecular features of familiar odors by mitral cells in the olfactory bulb, and synthetic coding of multiple coincident odorant features into odor objects by cortical neurons. In this paper, data are reviewed that show the critical role of acetylcholine (Ach) in olfactory system function and plasticity, and cholinergic modulation of olfactory perceptual learning at both the behavioral and cortical level. PMID:14747514

  18. Development of the olfactory pathways in platypus and echidna.

    PubMed

    Ashwell, Ken W S

    2012-01-01

    The two groups of living monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum für Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching. PMID:22156550

  19. Olfactory perceptual stability and discrimination.

    PubMed

    Barnes, Dylan C; Hofacer, Rylon D; Zaman, Ashiq R; Rennaker, Robert L; Wilson, Donald A

    2008-12-01

    No two roses smell exactly alike, but our brain accurately bundles these variations into a single percept 'rose'. We found that ensembles of rat olfactory bulb neurons decorrelate complex mixtures that vary by as little as a single missing component, whereas olfactory (piriform) cortical neural ensembles perform pattern completion in response to an absent component, essentially filling in the missing information and allowing perceptual stability. This piriform cortical ensemble activity predicts olfactory perception. PMID:18978781

  20. Attention and olfactory consciousness.

    PubMed

    Keller, Andreas

    2011-01-01

    Understanding the relation between attention and consciousness is an important part of our understanding of consciousness. Attention, unlike consciousness, can be systematically manipulated in psychophysical experiments and a law-like relation between attention and consciousness is waiting to be discovered. Most attempts to discover the nature of this relation are focused on a special type of attention: spatial visual attention. In this review I want to introduce another type of attention to the discussion: attention to the olfactory modality. I will first clarify the position of attention to smells in a general taxonomy of attention. I will then review the mechanisms and neuroanatomy of attention and consciousness in the olfactory system before using the newly introduced system to provide evidence that attention is necessary for consciousness. PMID:22203813

  1. Recent Trend in Development of Olfactory Displays

    NASA Astrophysics Data System (ADS)

    Yanagida, Yasuyuki

    An olfactory display is a device that generates scented air with desired concentration of aroma, and delivers it to the user's olfactory organ. In this article, the nature of olfaction is briefly described from the view point of how to configure olfactory displays. Next, component technologies to compose olfactory displays, i.e., making scents and delivering scents, are categorized. Several existing olfactory display systems are introduced to show the current status of research and development of olfactory displays.

  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. PMID:18777568

  3. The spatiotemporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.

    PubMed

    Vastagh, Csaba; Schwirtlich, Marija; Kwakowsky, Andrea; Erdélyi, Ferenc; Margolis, Frank L; Yanagawa, Yuchio; Katarova, Zoya; Szabó, Gábor

    2015-03-01

    Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. PMID:25125027

  4. Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

    PubMed

    Ohm, T G; Braak, E; Probst, A; Weindl, A

    1988-06-01

    Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells. PMID:3251589

  5. Enhanced trapping of stable flies via olfactory and visual cues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult stable flies are highly attracted to the so-called Alsynite cylinder trap; however this trap is expensive. Here we report the development of a cheaper and better white panel trap with options of adding visual and olfactory stimuli for enhanced stable fly trapping. The white panel trap attracte...

  6. Both olfactory epithelial and vomeronasal inputs are essential for activation of the medial amygdala and preoptic neurons of male rats.

    PubMed

    Dhungel, S; Masaoka, M; Rai, D; Kondo, Y; Sakuma, Y

    2011-12-29

    Chemosensory inputs signaling volatile and nonvolatile molecules play a pivotal role in sexual and social behavior in rodents. We have demonstrated that olfactory preference in male rats, that is, attraction to receptive female odors, is regulated by the medial amygdala (MeA), the cortical amygdala (CoA), and the preoptic area (POA). In this paper, we investigated the involvement of two chemosensory organs, the olfactory epithelium (OE) and the vomeronasal organ (VNO), in olfactory preference and copulatory behavior in male rats. We found that olfactory preferences were impaired by zinc sulfate lesion of the OE but not surgical removal of the VNO. Copulatory behaviors, especially intromission frequency and ejaculation, were also suppressed by zinc sulfate treatment. Neuronal activation in the accessory olfactory bulb (AOB), the MeA, the CoA, and the POA was analyzed after stimulation by airborne odors or soiled bedding of estrous females using cFos immunohistochemistry. Although the OE and VNO belong to different neural systems, the main and accessory olfactory systems, respectively, both OE lesion and VNO removal almost equally suppressed the number of cFos-immunoreactive cells in those areas that regulate olfactory preference. These results suggest that signals received by the OE and VNO interact and converge in the early stage of olfactory processing, in the AOB and its targets, although they have distinct roles in the regulation of social behaviors. PMID:21983295

  7. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  8. Olfactory Stimuli Increase Presence in Virtual Environments

    PubMed Central

    Munyan, Benson G.; Neer, Sandra M.; Beidel, Deborah C.; Jentsch, Florian

    2016-01-01

    Background Exposure therapy (EXP) is the most empirically supported treatment for anxiety and trauma-related disorders. EXP consists of repeated exposure to a feared object or situation in the absence of the feared outcome in order to extinguish associated anxiety. Key to the success of EXP is the need to present the feared object/event/situation in as much detail and utilizing as many sensory modalities as possible, in order to augment the sense of presence during exposure sessions. Various technologies used to augment the exposure therapy process by presenting multi-sensory cues (e.g., sights, smells, sounds). Studies have shown that scents can elicit emotionally charged memories, but no prior research has examined the effect of olfactory stimuli upon the patient’s sense of presence during simulated exposure tasks. Methods 60 adult participants navigated a mildly anxiety-producing virtual environment (VE) similar to those used in the treatment of anxiety disorders. Participants had no autobiographical memory associated with the VE. State anxiety, Presence ratings, and electrodermal (EDA) activity were collected throughout the experiment. Results Utilizing a Bonferroni corrected Linear Mixed Model, our results showed statistically significant relationships between olfactory stimuli and presence as assessed by both the Igroup Presence Questionnaire (IPQ: R2 = 0.85, (F(3,52) = 6.625, p = 0.0007) and a single item visual-analogue scale (R2 = 0.85, (F(3,52) = 5.382, p = 0.0027). State anxiety was unaffected by the presence or absence of olfactory cues. EDA was unaffected by experimental condition. Conclusion Olfactory stimuli increase presence in virtual environments that approximate those typical in exposure therapy, but did not increase EDA. Additionally, once administered, the removal of scents resulted in a disproportionate decrease in presence. Implications for incorporating the use of scents to increase the efficacy of exposure therapy is discussed. PMID

  9. Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

    PubMed Central

    Lin, Weihong; Margolskee, Robert; Donnert, Gerald; Hell, Stefan W.; Restrepo, Diego

    2007-01-01

    Olfactory sensory neurons (OSNs) in the main olfactory epithelium respond to environmental odorants. Recent studies reveal that these OSNs also respond to semiochemicals such as pheromones and that main olfactory input modulates animal reproduction, but the transduction mechanism for these chemosignals is not fully understood. Previously, we determined that responses to putative pheromones in the main olfactory system were reduced but not eliminated in mice defective for the canonical cAMP transduction pathway, and we suggested, on the basis of pharmacology, an involvement of phospholipase C. In the present study, we find that a downstream signaling component of the phospholipase C pathway, the transient receptor potential channel M5 (TRPM5), is coexpressed with the cyclic nucleotide-gated channel subunit A2 in a subset of mature OSNs. These neurons project axons primarily to the ventral olfactory bulb, where information from urine and other socially relevant signals is processed. We find that these chemosignals activate a subset of glomeruli targeted by TRPM5-expressing OSNs. Our data indicate that TRPM5-expressing OSNs that project axons to glomeruli in the ventral area of the main olfactory bulb are involved in processing of information from semiochemicals. PMID:17267604

  10. Once and again: retinoic acid signaling in the developing and regenerating olfactory pathway.

    PubMed

    Rawson, N E; LaMantia, A-S

    2006-06-01

    Retinoic acid (RA), a member of the steroid/thyroid superfamily of signaling molecules, is an essential regulator of morphogenesis, differentiation, and regeneration in the mammalian olfactory pathway. RA-mediated teratogenesis dramatically alters olfactory pathway development, presumably by disrupting retinoid-mediated inductive signaling that influences initial olfactory epithelium (OE) and bulb (OB) morphogenesis. Subsequently, RA modulates the genesis, growth, or stability of subsets of OE cells and OB interneurons. RA receptors, cofactors, and synthetic enzymes are expressed in the OE, OB, and anterior subventricular zone (SVZ), the site of neural precursors that generate new OB interneurons throughout adulthood. Their expression apparently accommodates RA signaling in OE cells, OB interneurons, and slowly dividing SVZ neural precursors. Deficiency of vitamin A, the dietary metabolic RA precursor, leads to cytological changes in the OE, as well as olfactory sensory deficits. Vitamin A therapy in animals with olfactory system damage can accelerate functional recovery. RA-related pathology as well as its potential therapeutic activity may reflect endogenous retinoid regulation of neuronal differentiation, stability, or regeneration in the olfactory pathway from embryogenesis through adulthood. These influences may be in register with retinoid effects on immune responses, metabolism, and modulation of food intake. PMID:16688760

  11. Otx2 expression and implications for olfactory imprinting in the anemonefish, Amphiprion percula.

    PubMed

    Veilleux, Heather D; Van Herwerden, Lynne; Cole, Nicholas J; Don, Emily K; De Santis, Christian; Dixson, Danielle L; Wenger, Amelia S; Munday, Philip L

    2013-01-01

    The otx2 gene encodes a transcription factor (OTX2) essential in the formation of the brain and sensory systems. Specifically, OTX2-positive cells are associated with axons in the olfactory system of mice and otx2 is upregulated in odour-exposed zebrafish, indicating a possible role in olfactory imprinting. In this study, otx2 was used as a candidate gene to investigate the molecular mechanisms of olfactory imprinting to settlement cues in the coral reef anemonefish, Amphiprion percula. The A. percula otx2 (Ap-otx2) gene was elucidated, validated, and its expression tested in settlement-stage A. percula by exposing them to behaviourally relevant olfactory settlement cues in the first 24 hours post-hatching, or daily throughout the larval phase. In-situ hybridisation revealed expression of Ap-otx2 throughout the olfactory epithelium with increased transcript staining in odour-exposed settlement-stage larval fish compared to no-odour controls, in all scenarios. This suggests that Ap-otx2 may be involved in olfactory imprinting to behaviourally relevant settlement odours in A. percula. PMID:24143277

  12. Otx2 expression and implications for olfactory imprinting in the anemonefish, Amphiprion percula

    PubMed Central

    Veilleux, Heather D.; Van Herwerden, Lynne; Cole, Nicholas J.; Don, Emily K.; De Santis, Christian; Dixson, Danielle L.; Wenger, Amelia S.; Munday, Philip L.

    2013-01-01

    Summary The otx2 gene encodes a transcription factor (OTX2) essential in the formation of the brain and sensory systems. Specifically, OTX2-positive cells are associated with axons in the olfactory system of mice and otx2 is upregulated in odour-exposed zebrafish, indicating a possible role in olfactory imprinting. In this study, otx2 was used as a candidate gene to investigate the molecular mechanisms of olfactory imprinting to settlement cues in the coral reef anemonefish, Amphiprion percula. The A. percula otx2 (Ap-otx2) gene was elucidated, validated, and its expression tested in settlement-stage A. percula by exposing them to behaviourally relevant olfactory settlement cues in the first 24 hours post-hatching, or daily throughout the larval phase. In-situ hybridisation revealed expression of Ap-otx2 throughout the olfactory epithelium with increased transcript staining in odour-exposed settlement-stage larval fish compared to no-odour controls, in all scenarios. This suggests that Ap-otx2 may be involved in olfactory imprinting to behaviourally relevant settlement odours in A. percula. PMID:24143277

  13. Calcium and olfactory transduction.

    PubMed

    Winegar, B D; Rosick, E R; Schafer, R

    1988-01-01

    1. Inorganic cations, organic calcium antagonists, and calmodulin antagonists were applied to olfactory epithelia of frogs (Rana pipiens) while recording electroolfactogram (EOG) responses. 2. Inorganic cations inhibited EOGs in a rank order, reflecting their calcium channel blocking potency: La3+ greater than Zn2+ greater than Cd2+ greater than Al3+ greater than Ca2+ greater than Sr2+ greater than Co2+ greater than Ba2+ greater than Mg2+. Barium ion significantly enhanced EOGs immediately following application. 3. Diltiazem and verapamil produced dose-dependent EOG inhibition. 4. Calmodulin antagonists inhibited EOGs without correlation to their anti-calmodulin potency. PMID:2904344

  14. Evidence for a Peripheral Olfactory Memory in Imprinted Salmon

    NASA Astrophysics Data System (ADS)

    Nevitt, Gabrielle A.; Dittman, Andrew H.; Quinn, Thomas P.; Moody, William J., Jr.

    1994-05-01

    The remarkable homing ability of salmon relies on olfactory cues, but its cellular basis is unknown. To test the role of peripheral olfactory receptors in odorant memory retention, we imprinted coho salmon (Oncorhynchus kisutch) to micromolar concentrations of phenyl ethyl alcohol during parr-smolt transformation. The following year, we measured phenyl ethyl alcohol responses in the peripheral receptor cells using patch clamp. Cells from imprinted fish showed increased sensitivity to phenyl ethyl alcohol compared either to cells from naive fish or to sensitivity to another behaviorally important odorant (L-serine). Field experiments verified an increased behavioral preference for phenyl ethyl alcohol by imprinted salmon as adults. Thus, some component of the imprinted olfactory homestream memory appears to be retained peripherally.

  15. Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis.

    PubMed

    Sourisseau, T; Desbois, C; Debure, L; Bowtell, D D; Cato, A C; Schneikert, J; Moyse, E; Michel, D

    2001-04-01

    Normal apoptosis occurs continuously in the olfactory neuroepithelium of adult vertebrates, making it a useful model for studying neuronal apoptosis. Here we demonstrate that overexpression of the anti-apoptotic Bag-1 gene in olfactory neuronal cells confers a strong resistance to apoptosis. Conversely decreased levels of Bag-1 were found to precede a massive wave of olfactory neuronal apoptosis triggered by synaptic target ablation. We show that the decrease is brought about by ubiquitination and subsequent degradation of the Bag-1 protein. The ring finger protein Siah-2 is a likely candidate for the ubiquitination reaction since Siah-2 mRNA accumulated in lesioned olfactory neuroepithelium and overexpression of Siah-2 stimulated Bag-1 ubiquitination and degradation in transient expression assays. These results together identify destabilization of Bag-1 as a necessary step in olfactory neuronal apoptosis. PMID:11257006

  16. Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons.

    PubMed

    Berghard, Anna; Hägglund, Anna-Carin; Bohm, Staffan; Carlsson, Leif

    2012-08-01

    Inactivation of the LIM-homeodomain 2 gene (Lhx2) results in a severe defect in specification of olfactory sensory neurons (OSNs). However, the ramifications of lack of Lhx2-dependent OSN specification for formation of the primary olfactory pathway have not been addressed, since mutant mice die in utero. We have analyzed prenatal and postnatal consequences of conditionally inactivating Lhx2 selectively in OSNs. A cell-autonomous effect is that OSN axons cannot innervate their target, the olfactory bulb. Moreover, the lack of Lhx2 in OSNs causes unpredicted, non-cell-autonomous phenotypes. First, the olfactory bulb shows pronounced hypoplasia in adults, and the data suggest that innervation by correctly specified OSNs is necessary for adult bulb size and organization. Second, absence of an olfactory nerve in the conditional mutant reveals that the vomeronasal nerve is dependent on olfactory nerve formation. Third, the lack of a proper vomeronasal nerve prevents migration of gonadotropin-releasing hormone (GnRH) cells the whole distance to their final positions in the hypothalamus during embryo development. As adults, the conditional mutants do not pass puberty, and these findings support the view of an exclusive nasal origin of GnRH neurons in the mouse. Thus, Lhx2 in OSNs is required for functional development of three separate systems. PMID:22581782

  17. Cloning and olfactory expression of progestin receptors in the Chinese black sleeper Bostrichthys sinensis.

    PubMed

    Zhang, Yu Ting; Liu, Dong Teng; Zhu, Yong; Chen, Shi Xi; Hong, Wan Shu

    2016-05-01

    Our previous studies suggested that 17α,20β-dihydroxy-4-pregnen-3-one (DHP), an oocyte maturation inducing progestin, also acts as a sex pheromone in Chinese black sleeper Bostrichthys sinensis, a fish species that inhabits intertidal zones and mates and spawns inside a muddy burrow. The electro-olfactogram response to DHP increased during the breeding season. In the present study, we cloned the cDNAs of the nine progestin receptors (pgr, paqr5, 6, 7(a, b), 8, 9, pgrmc1, 2) from B. sinensis, analyzed their tissue distribution, and determined the expression in the olfactory rosette during the reproductive cycle in female and male fish. The deduced amino acid sequences of the nine progestin receptors share high sequence identities with those of other fish species and relatively lower homology with their mammalian counterparts, and phylogenetic analyses classified the nine B. sinensis progestin receptors into their respective progestin receptor groups. Tissue distribution of B. sinensis progestin receptors showed differential expression patterns, but all these nine genes were expressed in the olfactory rosette. Interestingly, paqr5 mRNA was found in the intermediate and basal parts of the olfactory epithelium but not in the central core using in situ hybridization, and its expression level was the highest in the olfactory rosette among the tissues examined. These results suggested Paqr5 may have an important role for transmitting progestin signaling in the olfactory system. The expression levels of paqr7a and paqr7b, pgr and pgrmc2 mRNA peaked around the mid meiotic stage, and that of paqr8 peaked at late meiotic stage in the olfactory rosette in males, while the olfactory expression of paqr5 decreased gradually as spermatogenesis progressed. In contrast, the expression of the progestin receptors did not change significantly during the development of the ovary in the olfactory rosette in females, except that of pgr. Interestingly, the changes of paqr8 expression in

  18. Aggressive behaviour and physiological responses to pheromones are strongly impaired in mice deficient for the olfactory G-protein -subunit G8.

    PubMed

    Montani, Giorgia; Tonelli, Simone; Sanghez, Valentina; Ferrari, Pier Francesco; Palanza, Paola; Zimmer, Andreas; Tirindelli, Roberto

    2013-08-15

    Heterotrimeric G-proteins are critical players in the transduction mechanisms underlying odorant and pheromonal signalling. In the vomeronasal organ (VNO) of the adult mouse, two different G-protein complexes have been identified. Gαoβ2γ8 is preferentially expressed in the basal neurons and coexpresses with type-2 vomeronasal pheromone receptors (V2Rs) whereas Gαi2β2γ2 is found in the apical neurons and coexpresses with type-1 vomeronasal pheromone receptors (V1Rs). V2R-expressing neurons project to the posterior accessory olfactory bulb (AOB) whereas neurons expressing V1Rs send their axon to the anterior AOB. Gγ8 is also expressed in developing olfactory neurons where this protein is probably associated with Go. Here, we generated mice with a targeted deletion of the Gγ8 gene and investigated the behavioural effects and the physiological consequences of this mutation. Gγ8(-/-) mice show a normal development of the main olfactory epithelium; moreover, they do not display major deficits in odour perception. In contrast, the VNO undergoes a slow but remarkable loss of basal neurons starting from the fourth postnatal week, with a 40% reduction of cells at 2 months and 70% at 1 year. This loss is associated with a reduced early-gene expression in the posterior AOB of mice stimulated with pheromones. More interestingly, the Gγ8 deletion specifically leads to a reduced pheromone-mediated aggressiveness in both males and females, all other socio-sexual behaviours remaining unaltered. This study defines a specific role for Gγ8 in maintenance of the neuronal population of the VNO and in the mechanisms of pheromonal signalling that involve the aggressive behaviour towards conspecifics. PMID:23836683

  19. The Olfactory Transcriptomes of Mice

    PubMed Central

    Ibarra-Soria, Ximena; Levitin, Maria O.; Saraiva, Luis R.; Logan, Darren W.

    2014-01-01

    The olfactory (OR) and vomeronasal receptor (VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery. PMID:25187969

  20. Olfactory maps, circuits and computations.

    PubMed

    Giessel, Andrew J; Datta, Sandeep Robert

    2014-02-01

    Sensory information in the visual, auditory and somatosensory systems is organized topographically, with key sensory features ordered in space across neural sheets. Despite the existence of a spatially stereotyped map of odor identity within the olfactory bulb, it is unclear whether the higher olfactory cortex uses topography to organize information about smells. Here, we review recent work on the anatomy, microcircuitry and neuromodulation of two higher-order olfactory areas: the piriform cortex and the olfactory tubercle. The piriform is an archicortical region with an extensive local associational network that constructs representations of odor identity. The olfactory tubercle is an extension of the ventral striatum that may use reward-based learning rules to encode odor valence. We argue that in contrast to brain circuits for other sensory modalities, both the piriform and the olfactory tubercle largely discard any topography present in the bulb and instead use distributive afferent connectivity, local learning rules and input from neuromodulatory centers to build behaviorally relevant representations of olfactory stimuli. PMID:24492088

  1. The olfactory transcriptomes of mice.

    PubMed

    Ibarra-Soria, Ximena; Levitin, Maria O; Saraiva, Luis R; Logan, Darren W

    2014-09-01

    The olfactory (OR) and vomeronasal receptor (VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery. PMID:25187969

  2. Gonadotropin releasing hormone (GnRH)--a novel olfactory stimulant in fish.

    PubMed

    Andersen, O; Døving, K B

    1991-08-01

    The aim of this study was to elucidate the putative role of the gonadotropin releasing hormone (GnRH or LHRH) as an olfactory stimulant in fish. We report for the first time extreme sensitivity of the olfactory organ in the rainbow trout (Oncorhynchus mykiss) to GnRH. Recordings of the electroolfactogram (EOG) showed an electrophysiological response to 10(-16) M GnRH four times the amplitude of the response to a fresh water control stimulus. By stimulating the olfactory epithelium with several GnRH analogs and fragments of the decapeptide, the biologically active region of GnRH could be partly elucidated. The response profile of GnRH differed from that of the positive control odorant L-alanine, suggesting that separate receptors or receptor cells are involved. We propose that this potent odorant may act as a reproductive pheromone in fish. PMID:1912479

  3. Viral disruption of olfactory progenitors is exacerbated in allergic mice.

    PubMed

    Ueha, R; Mukherjee, S; Ueha, S; de Almeida Nagata, D E; Sakamoto, T; Kondo, K; Yamasoba, T; Lukacs, N W; Kunkel, S L

    2014-09-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance. PMID:24998164

  4. Chemotopic Odorant Coding in a Mammalian Olfactory System

    PubMed Central

    Johnson, Brett A.; Leon, Michael

    2008-01-01

    Systematic mapping studies involving 365 odorant chemicals have shown that glomerular responses in the rat olfactory bulb are organized spatially in patterns that are related to the chemistry of the odorant stimuli. This organization involves the spatial clustering of principal responses to numerous odorants that share key aspects of chemistry such as functional groups, hydrocarbon structural elements, and/or overall molecular properties related to water solubility. In several of the clusters, responses shift progressively in position according to odorant carbon chain length. These response domains appear to be constructed from orderly projections of sensory neurons in the olfactory epithelium and may also involve chromatography across the nasal mucosa. The spatial clustering of glomerular responses may serve to “tune” the principal responses of bulbar projection neurons by way of inhibitory interneuronal networks, allowing the projection neurons to respond to a narrower range of stimuli than their associated sensory neurons. When glomerular activity patterns are viewed relative to the overall level of glomerular activation, the patterns accurately predict the perception of odor quality, thereby supporting the notion that spatial patterns of activity are the key factors underlying that aspect of the olfactory code. A critical analysis suggests that alternative coding mechanisms for odor quality, such as those based on temporal patterns of responses, enjoy little experimental support. PMID:17480025

  5. Olfactory responses to explosives associated odorants are enhanced by zinc nanoparticles.

    PubMed

    Moore, Christopher H; Pustovyy, Oleg; Dennis, John C; Moore, Timothy; Morrison, Edward E; Vodyanoy, Vitaly J

    2012-01-15

    Many odorants related to manufactured explosives have low volatilities and are barely detectable as odors. We previously reported that zinc metal nanoparticles increased rat olfactory epithelium responses, measured by electroolfactogram (EOG), to several odorants. Here, we report that nanomolar concentrations of zinc metal nanoparticles strongly enhanced olfactory responses to the explosives related odorants cyclohexanone, methyl benzoate, acetophenone, and eugenol. Rat olfactory epithelium was exposed to metal nanoparticles and odorant responses were quantified by EOG. Zinc nanoparticles added to explosive odorants strongly increased the odorant response in a dose-dependent manner. The enzymatic breakdown of the second messenger cyclic adenosine monophosphate (cAMP) was prevented by adding the membrane-permeable phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). This caused the olfactory cilia cAMP concentration to increase and generated EOG signals. The EOG responses generated by IBMX were not enhanced by zinc nanoparticles. Based on these observations, we conclude that zinc nanoparticles act at the receptor site and are involved in the initial events of olfaction. Our results suggest that zinc metal nanoparticles can be used to facilitate a canine detection of explosive odorants. PMID:22265566

  6. Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream.

    PubMed

    Gliem, Sebastian; Syed, Adnan S; Sansone, Alfredo; Kludt, Eugen; Tantalaki, Evangelia; Hassenklöver, Thomas; Korsching, Sigrun I; Manzini, Ivan

    2013-06-01

    In contrast to the single sensory surface present in teleost fishes, several spatially segregated subsystems with distinct molecular and functional characteristics define the mammalian olfactory system. However, the evolutionary steps of that transition remain unknown. Here we analyzed the olfactory system of an early diverging tetrapod, the amphibian Xenopus laevis, and report for the first time the existence of two odor-processing streams, sharply segregated in the main olfactory bulb and partially segregated in the olfactory epithelium of pre-metamorphic larvae. A lateral odor-processing stream is formed by microvillous receptor neurons and is characterized by amino acid responses and Gαo/Gαi as probable signal transducers, whereas a medial stream formed by ciliated receptor neurons is characterized by responses to alcohols, aldehydes, and ketones, and Gαolf/cAMP as probable signal transducers. To reveal candidates for the olfactory receptors underlying these two streams, the spatial distribution of 12 genes from four olfactory receptor gene families was determined. Several class II and some class I odorant receptors (ORs) mimic the spatial distribution observed for the medial stream, whereas a trace amine-associated receptor closely parallels the spatial pattern of the lateral odor-processing stream. Other olfactory receptors (some class I odorant receptors and vomeronasal type 1 receptors) and odor responses (to bile acids, amines) were not lateralized, the latter not even in the olfactory bulb, suggesting an incomplete segregation. Thus, the olfactory system of X. laevis exhibits an intermediate stage of segregation and as such appears well suited to investigate the molecular driving forces behind olfactory regionalization. PMID:23269434

  7. The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

    PubMed Central

    2007-01-01

    Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use. PMID:17903277

  8. Assessment of olfactory function.

    PubMed

    Hummel, Thomas; Welge-Lüessen, Antje

    2006-01-01

    Numerous techniques are available for the investigation of chemosensory functions in humans. They include psychophysical measures of chemosensory function, e.g. odor identification, odor discrimination, odor thresholds, odor memory, and retronasal perception of odors. In order to assess changes related to the patients' quality of life or effects of qualitative olfactory dysfunction, questionnaires are being used. Measures relying to a lesser degree on the subjects' cooperation are e.g. chemosensory event-related potentials, odor-induced changes of the EEG, the electroolfactogram, imaging techniques, or measures of respiration. In a clinical context, however, psychophysical techniques are most frequently used, e.g. tests for odor identification, and odor thresholds. Interpretation of results from these measures is frequently supported by the assessment of chemosensory event-related potentials. Other techniques await further standardization before they will become useful in a clinical context. PMID:16733334

  9. Olfactory receptor signaling.

    PubMed

    Antunes, Gabriela; Simoes de Souza, Fabio Marques

    2016-01-01

    The guanine nucleotide protein (G protein)-coupled receptors (GPCRs) superfamily represents the largest class of membrane protein in the human genome. More than a half of all GPCRs are dedicated to interact with odorants and are termed odorant-receptors (ORs). Linda Buck and Richard Axel, the Nobel Prize laureates in physiology or medicine in 2004, first cloned and characterized the gene family that encode ORs, establishing the foundations to the understanding of the molecular basis for odor recognition. In the last decades, a lot of progress has been done to unravel the functioning of the sense of smell. This chapter gives a general overview of the topic of olfactory receptor signaling and reviews recent advances in this field. PMID:26928542

  10. acj6: a gene affecting olfactory physiology and behavior in Drosophila.

    PubMed Central

    Ayer, R K; Carlson, J

    1991-01-01

    Mutations affecting olfactory behavior provide material for use in molecular studies of olfaction in Drosophila melanogaster. Using the electroantennogram (EAG), a measure of antennal physiology, we have found an adult antennal defect in the olfactory behavioral mutant abnormal chemosensory jump 6 (acj6). The acj6 EAG defect was mapped to a single locus and the same mutation was found to be responsible for both reduction in EAG amplitude and diminished behavioral response, as if reduced antennal responsiveness to odorant is responsible for abnormal chemosensory behavior in the mutant. acj6 larval olfactory behavior is also abnormal; the mutation seems to alter cellular processes necessary for olfaction at both developmental stages. The acj6 mutation exhibits specificity in that visual system function appears normal in larvae and adults. These experiments provide evidence that the acj6 gene encodes a product required for olfactory signal transduction. Images PMID:1905022

  11. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  12. Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval Xenopus laevis

    PubMed Central

    Sansone, Alfredo; Syed, Adnan S.; Tantalaki, Evangelia; Korsching, Sigrun I.; Manzini, Ivan

    2014-01-01

    Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal epithelium is first observed in amphibians. In contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. The transient receptor potential channel TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red-legged salamander (Plethodon shermani). Here we examined the localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2 gene. We show that it is expressed in both the MOE and the vomeronasal epithelium. This is the first description of a broad trpc2 expression in the MOE of a tetrapod. The expression pattern of trpc2 in the MOE is virtually undistinguishable from that of MOE-specific v2rs, indicating that they are co-expressed in the same neuronal subpopulation. PMID:24737764

  13. Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval Xenopus laevis.

    PubMed

    Sansone, Alfredo; Syed, Adnan S; Tantalaki, Evangelia; Korsching, Sigrun I; Manzini, Ivan

    2014-07-01

    Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal epithelium is first observed in amphibians. In contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. The transient receptor potential channel TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red-legged salamander (Plethodon shermani). Here we examined the localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2 gene. We show that it is expressed in both the MOE and the vomeronasal epithelium. This is the first description of a broad trpc2 expression in the MOE of a tetrapod. The expression pattern of trpc2 in the MOE is virtually undistinguishable from that of MOE-specific v2rs, indicating that they are co-expressed in the same neuronal subpopulation. PMID:24737764

  14. A TAP1 null mutation leads to an enlarged olfactory bulb and supernumerary, ectopic olfactory glomeruli

    PubMed Central

    Salcedo, Ernesto; Cruz, Nicole M.; Ly, Xuan; Welander, Beth A.; Hanson, Kyle; Kronberg, Eugene; Restrepo, Diego

    2013-01-01

    Major histocompatibility class I (MHCI) molecules are well known for their immunological role in mediating tissue graft rejection. Recently, these molecules were discovered to be expressed in distinct neuronal subclasses, dispelling the long-held tenet that the uninjured brain is immune-privileged. Here, we show that MHCI molecules are expressed in the main olfactory bulb (MOB) of adult animals. Furthermore, we find that mice with diminished levels of MHCI expression have enlarged MOBs containing an increased number of small, morphologically abnormal and ectopically located P2 glomeruli. These findings suggest that MHCI molecules may play an important role in the proper formation of glomeruli in the bulb. PMID:23697805

  15. SVZ-derived newly generated neurons populate several olfactory and limbic forebrain regions

    PubMed Central

    Shapiro, Lee A.; Ng, Kwan; Zhou, Qun-Yong; Ribak, Charles E.

    2009-01-01

    Neurogenesis persists in several regions of the adult mammalian brain. Although the hippocampus and olfactory bulb are most commonly studied in the context of adult neurogenesis, there is an increasing body of evidence in support of neurogenesis occurring outside of these two regions. The current study expands upon previous data by showing newborn neurons with a mature phenotype are located in several olfactory and limbic structures outside of the hippocampus and olfactory bulb, where we previously described DCX/BrdU immature neurons. Notably, newborn neurons with a mature neuronal phenotype are found in the olfactory tubercles, anterior olfactory nuclei, tenia tecta, islands of Calleja, amygdala and lateral entorhinal cortex. The appearance of newborn neurons with a mature phenotype in these regions suggests that these structures are destinations, and that newborn neurons are not simply passing through these structures. In light of the increasing body of evidence for neurogenesis in these, and other olfactory, limbic and striatal structures, we hypothesize that brain regions displaying adult neurogenesis are functionally linked. PMID:18849007

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

    PubMed

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

    2008-10-22

    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 gamma-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

  17. Flash Photolysis of Caged Compounds in the Cilia of Olfactory Sensory Neurons

    PubMed Central

    Boccaccio, Anna; Sagheddu, Claudia; Menini, Anna

    2011-01-01

    Photolysis of caged compounds allows the production of rapid and localized increases in the concentration of various physiologically active compounds1. Caged compounds are molecules made physiologically inactive by a chemical cage that can be broken by a flash of ultraviolet light. Here, we show how to obtain patch-clamp recordings combined with photolysis of caged compounds for the study of olfactory transduction in dissociated mouse olfactory sensory neurons. The process of olfactory transduction (Figure 1) takes place in the cilia of olfactory sensory neurons, where odorant binding to receptors leads to the increase of cAMP that opens cyclic nucleotide-gated (CNG) channels2. Ca entry through CNG channels activates Ca-activated Cl channels. We show how to dissociate neurons from the mouse olfactory epithelium3 and how to activate CNG channels or Ca-activated Cl channels by photolysis of caged cAMP4 or caged Ca5. We use a flash lamp6,7 to apply ultraviolet flashes to the ciliary region to uncage cAMP or Ca while patch-clamp recordings are taken to measure the current in the whole-cell voltage-clamp configuration8-11. PMID:22064384

  18. Vasoactive intestinal polypeptide mediates circadian rhythms in mammalian olfactory bulb and olfaction.

    PubMed

    Miller, Jae-Eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E; Herzog, Erik D

    2014-04-23

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system. PMID:24760863

  19. Vasoactive Intestinal Polypeptide Mediates Circadian Rhythms in Mammalian Olfactory Bulb and Olfaction

    PubMed Central

    Miller, Jae-eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E.

    2014-01-01

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system. PMID:24760863

  20. Processing by the main olfactory system of chemosignals that facilitate mammalian reproduction.

    PubMed

    Baum, Michael J; Cherry, James A

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". Most mammalian species possess two parallel circuits that process olfactory information. One of these circuits, the accessory system, originates with sensory neurons in the vomeronasal organ (VNO). This system has long been known to detect non-volatile pheromonal odorants from conspecifics that influence numerous aspects of social communication, including sexual attraction and mating as well as the release of luteinizing hormone from the pituitary gland. A second circuit, the main olfactory system, originates with sensory neurons in the main olfactory epithelium (MOE). This system detects a wide range of non-pheromonal odors relevant to survival (e.g., food and predator odors). Over the past decade evidence has accrued showing that the main olfactory system also detects a range of volatile odorants that function as pheromones to facilitate mate recognition and activate the hypothalamic-pituitary-gonadal neuroendocrine axis. We review early studies as well as the new literature supporting the view that the main olfactory system processes a variety of different pheromonal cues that facilitate mammalian reproduction. PMID:24929017

  1. Identification and functional analysis of olfactory receptor family reveal unusual characteristics of the olfactory system in the migratory locust.

    PubMed

    Wang, Zhifeng; Yang, Pengcheng; Chen, Dafeng; Jiang, Feng; Li, Yan; Wang, Xianhui; Kang, Le

    2015-11-01

    Locusts represent the excellent model of insect olfaction because the animals are equipped with an unusual olfactory system and display remarkable density-dependent olfactory plasticity. However, information regarding receptor molecules involved in the olfactory perception of locusts is very limited. On the basis of genome sequence and antennal transcriptome of the migratory locust, we conduct the identification and functional analysis of two olfactory receptor families: odorant receptors (ORs) and ionotropic receptors (IRs). In the migratory locust, there is an expansion of OR family (142 ORs) while distinctly lower number of IR genes (32 IRs) compared to the repertoires of other insects. The number of the locust OR genes is much less than that of glomeruli in antennal lobe, challenging the general principle of the "one glomerulus-one receptor" observed in other insects. Most OR genes are found in tandem arrays, forming two large lineage-specific subfamilies in the phylogenetic tree. The "divergent IR" subfamily displays a significant contraction, and most of the IRs belong to the "antennal IR" subfamily in the locust. Most ORs/IRs have olfactory-specific expression while some broadly- or internal-expressed members are also found. Differing from holometabolous insects, the migratory locust contains very similar expression profiles of ORs/IRs between nymph and adult stages. RNA interference and behavioral assays indicate that an OR-based signaling pathway, not IR-based, mediates the attraction of locusts to aggregation pheromones. These discoveries provide insights into the unusual olfactory system of locusts and enhance our understanding of the evolution of insect olfaction. PMID:26265180

  2. Sendai Virus Induces Persistent Olfactory Dysfunction in a Murine Model of PVOD via Effects on Apoptosis, Cell Proliferation, and Response to Odorants

    PubMed Central

    Tian, Jun; Pinto, Jayant M.; Cui, Xiaolan; Zhang, Henghui; Li, Li; Liu, Yulong; Wu, Chan; Wei, Yongxiang

    2016-01-01

    Background Viral infection is a common cause of olfactory dysfunction. The complexities of studying post-viral olfactory loss in humans have impaired further progress in understanding the underlying mechanism. Recently, evidence from clinical studies has implicated Parainfluenza virus 3 as a causal agent. An animal model of post viral olfactory disorders (PVOD) would allow better understanding of disease pathogenesis and represent a major advance in the field. Objective To develop a mouse model of PVOD by evaluating the effects of Sendai virus (SeV), the murine counterpart of Parainfluenza virus, on olfactory function and regenerative ability of the olfactory epithelium. Methods C57BL/6 mice (6–8 months old) were inoculated intranasally with SeV or ultraviolet (UV)-inactivated virus (UV-SeV). On days 3, 10, 15, 30 and 60 post-infection, olfactory epithelium was harvested and analyzed by histopathology and immunohistochemical detection of S-phase nuclei. We also measured apoptosis by TUNEL assay and viral load by real-time PCR. The buried food test (BFT) was used to measure olfactory function of mice at day 60. In parallel, cultured murine olfactory sensory neurons (OSNs) infected with SeV or UV-SeV were tested for odorant-mixture response by measuring changes in intracellular calcium concentrations indicated by fura-4 AM assay. Results Mice infected with SeV suffered from olfactory dysfunction, peaking on day 15, with no loss observed with UV-SeV. At 60 days, four out of 12 mice infected with SeV still had not recovered, with continued normal function in controls. Viral copies of SeV persisted in both the olfactory epithelium (OE) and the olfactory bulb (OB) for at least 60 days. At day 10 and after, both unit length labeling index (ULLI) of apoptosis and ULLI of proliferation in the SeV group was markedly less than the UV-SeV group. In primary cultured OSNs infected by SeV, the percentage of cells responding to mixed odors was markedly lower in the SeV group

  3. [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. PMID:21879170

  4. Integration of Visual and Olfactory Cues in Host Plant Identification by the Asian Longhorned Beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae).

    PubMed

    Yv, Fei L; Hai, Xiaoxia; Wang, Zhigang; Yan, Aihua; Liu, Bingxiang; Bi, Yongguo

    2015-01-01

    Some insects use host and mate cues, including odor, color, and shape, to locate and recognize their preferred hosts and mates. Previous research has shown that the Asian longicorn beetle, Anoplophora glabripennis (Motschulsky), uses olfactory cues to locate host plants and differentiate them from non-host plants. However, whether A. glabripennis adults use visual cues or a combination of visual and olfactory cues remains unclear. In this study, we tested the host location and recognition behavior in A. glabripennis, which infests a number of hardwood species and causes considerable economic losses in North America, Europe and Asia. We determined the relative importance of visual and olfactory cues from Acer negundo in host plant location and recognition, as well as in the discrimination of non-host plants (Sabina chinensis and Pinus bungeana), by female and male A. glabripennis. Visual and olfactory cues from the host plants (A. negundo), alone and combined, attracted significantly more females and males than equivalent cues from non-host plants (S. chinensis and P. bungeana). Furthermore, the combination of visual and olfactory cues of host plants attracted more adults than either cue alone, and visual cues alone attracted significantly more adults than olfactory cues alone. This finding suggests that adult A. glabripennis has an innate preference for the visual and/or olfactory cues of its host plants (A. negundo) over those of the non-host plant and visual cues are initially more important than olfactory cues for orientation; furthermore, this finding also suggests that adults integrate visual and olfactory cues to find their host plants. Our results indicate that different modalities of host plant cues should be considered together to understand fully the communication between host plants and Asian longhorned beetles. PMID:26556100

  5. Integration of Visual and Olfactory Cues in Host Plant Identification by the Asian Longhorned Beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae)

    PubMed Central

    L.Yv, Fei; Hai, Xiaoxia; Wang, Zhigang; Yan, Aihua; Liu, Bingxiang; Bi, Yongguo

    2015-01-01

    Some insects use host and mate cues, including odor, color, and shape, to locate and recognize their preferred hosts and mates. Previous research has shown that the Asian longicorn beetle, Anoplophora glabripennis (Motschulsky), uses olfactory cues to locate host plants and differentiate them from non-host plants. However, whether A. glabripennis adults use visual cues or a combination of visual and olfactory cues remains unclear. In this study, we tested the host location and recognition behavior in A. glabripennis, which infests a number of hardwood species and causes considerable economic losses in North America, Europe and Asia. We determined the relative importance of visual and olfactory cues from Acer negundo in host plant location and recognition, as well as in the discrimination of non-host plants (Sabina chinensis and Pinus bungeana), by female and male A. glabripennis. Visual and olfactory cues from the host plants (A. negundo), alone and combined, attracted significantly more females and males than equivalent cues from non-host plants (S. chinensis and P. bungeana). Furthermore, the combination of visual and olfactory cues of host plants attracted more adults than either cue alone, and visual cues alone attracted significantly more adults than olfactory cues alone. This finding suggests that adult A. glabripennis has an innate preference for the visual and/or olfactory cues of its host plants (A. negundo) over those of the non-host plant and visual cues are initially more important than olfactory cues for orientation; furthermore, this finding also suggests that adults integrate visual and olfactory cues to find their host plants. Our results indicate that different modalities of host plant cues should be considered together to understand fully the communication between host plants and Asian longhorned beetles. PMID:26556100

  6. Evolution of insect olfactory receptors

    PubMed Central

    Missbach, Christine; Dweck, Hany KM; Vogel, Heiko; Vilcinskas, Andreas; Stensmyr, Marcus C; Hansson, Bill S; Grosse-Wilde, Ewald

    2014-01-01

    The olfactory sense detects a plethora of behaviorally relevant odor molecules; gene families involved in olfaction exhibit high diversity in different animal phyla. Insects detect volatile molecules using olfactory (OR) or ionotropic receptors (IR) and in some cases gustatory receptors (GRs). While IRs are expressed in olfactory organs across Protostomia, ORs have been hypothesized to be an adaptation to a terrestrial insect lifestyle. We investigated the olfactory system of the primary wingless bristletail Lepismachilis y-signata (Archaeognatha), the firebrat Thermobia domestica (Zygentoma) and the neopteran leaf insect Phyllium siccifolium (Phasmatodea). ORs and the olfactory coreceptor (Orco) are with very high probability lacking in Lepismachilis; in Thermobia we have identified three Orco candidates, and in Phyllium a fully developed OR/Orco-based system. We suggest that ORs did not arise as an adaptation to a terrestrial lifestyle, but evolved later in insect evolution, with Orco being present before the appearance of ORs. DOI: http://dx.doi.org/10.7554/eLife.02115.001 PMID:24670956

  7. Somatostatin-14-like immunoreactive neurons and fibres in the human olfactory bulb.

    PubMed

    Ohm, T G; Braak, E; Probst, A

    1988-01-01

    This study describes the morphological features and the distribution pattern of neurons in the human olfactory bulb which are immunoreactive for an antiserum against the neuropeptide somatostatin-14. Immunoreactive nerve cell bodies were mainly found in the white matter surrounding the cell clusters of the anterior olfactory nucleus. Some immunoreactive neurons were also found scattered throughout the anterior olfactory nucleus and the deeper parts of the inner granule cell layer. Only a few immunoreactive neurons were localized in the glomerular layer and the outer granule cell layer. Immunoreactive fibres were found in all layers of the olfactory bulb. In addition, an impressive number of coiled and kinked immunoreactive fibres were localized within the anterior olfactory nucleus forming a dense plexus. Accumulations of twisted and coiled branches of immunoreactive fibres were rarely found either surrounding or within the olfactory glomerula. The characteristics of somatostatin-14 immunoreactive neurons as seen in the combined pigment-Nissl preparation were studied after decolourizing the chromogen and restaining the preparations with aldehydefuchsin in order to demonstrate the lipofuscin pigment and gallocyanin chrome alum for Nissl material. About 90% of the immunoreactive neurons studied in this manner turned out to be devoid of lipofuscin granules. The remaining 10% displayed different patterns of pigmentation. These findings suggest the presence of different types of somatostatin-14-like immunoreactive neurons in the olfactory bulb of the human adult. PMID:2906788

  8. Assessing olfactory performance in a New World primate, Saimiri sciureus.

    PubMed

    Laska, M; Hudson, R

    1993-01-01

    Using a task designed to simulate olfactory-guided foraging behavior, this study demonstrates for the first time that olfactory performance can be reliably assessed in squirrel monkeys. Small flip-top vials were fixed in random order to the arms of a climbing frame and equipped with odorized strips signalling either that they contained a peanut food reward (S+) or that they did not (S-), and three adult female monkeys were allowed 1 min to harvest as many baited nuts from this tree as possible. Given five 1-min trials per day, animals took between 15 and 25 days to reach the criterion of 80% correct choices, could readily transfer to new S+ or S- stimuli, and could remember the task even after a 1-month break. The precision and consistency of the monkeys' performance in tests of discrimination ability and sensitivity demonstrate the suitability of this paradigm for assessing olfactory function, and a first test of human subjects using the same cups and odorants showed that it may also be used to directly compare olfactory performance in human and nonhuman primates. PMID:8434074

  9. Olfactory morphology and physiology of elasmobranchs.

    PubMed

    Meredith, Tricia L; Kajiura, Stephen M

    2010-10-15

    Elasmobranch fishes are thought to possess greater olfactory sensitivities than teleost fishes due in part to the large amount of epithelial surface area that comprises their olfactory organs; however, direct evidence correlating the size of the olfactory organ to olfactory sensitivity is lacking. This study examined the olfactory morphology and physiology of five distantly related elasmobranch species. Specifically, we quantified the number of lamellae and lamellar surface area (as if it were a flat sheet, not considering secondary lamellae) that comprise their olfactory organs. We also calculated the olfactory thresholds and relative effectiveness of amino acid odorants for each species. The olfactory organs varied in both the number of lamellae and lamellar surface area, which may be related to their general habitat, but neither correlated with olfactory threshold. Thresholds to amino acid odorants, major olfactory stimuli of all fishes, ranged from 10⁻⁹·⁰ to 10⁻⁶·⁹ mol l⁻¹, which indicates that these elasmobranch species demonstrate comparable thresholds with teleosts. In addition, the relative effectiveness of amino acid stimuli to the olfactory organ of elasmobranchs is similar to that previously described in teleosts with neutral amino acids eliciting significantly greater responses than others. Collectively, these results indicate parallels in olfactory physiology between these two groups of fishes. PMID:20889825

  10. Olfactory dysfunction in patients with multiple sclerosis.

    PubMed

    Li, Li-Min; Yang, Li-Na; Zhang, Lin-Jie; Fu, Ying; Li, Ting; Qi, Yuan; Wang, Jing; Zhang, Da-Qi; Zhang, Ningnannan; Liu, Jingchun; Yang, Li

    2016-06-15

    Association of changes in olfactory-related structures with olfactory function in patients with multiple sclerosis (MS) is not well understood. We used a T&T olfactometer test kit to evaluate olfactory function in 26 patients with MS and 26 age- and sex-matched healthy controls (HC). Then, Brain MRI were performed and olfactory-related structures were analyzed in these subjects. Olfactory detection and recognition threshold were significantly higher in the MS group, interestingly olfactory recognition threshold positively correlated with expanded disability status scale scores in these patients. Olfactory bulb (OB) volume reduced in patients with olfactory dysfunction (ODF). At the same time, reductions in gray matter (GM) volume were observed in the parahippocampal gyrus (PCG), amygdala, piriform cortex, and inferior frontal gyrus in patients with MS compared to HC. Atrophy of the PCG was more obvious in patients with ODF than patients without ODF and the PCG volume correlated with the olfactory recognition threshold, while no difference was found in fractional anisotropy values of tract-based spatial statistics analysis in the two groups. Olfactory function in patients with MS tends to become gradually more impaired with disability aggravation. Decreases in the volume of the OB and olfactory-related GM might provide valuable information about disease status in patients with MS with olfactory impairment. PMID:27206870

  11. Sniffing and Oxytocin: Effects on Olfactory Memories.

    PubMed

    Stoop, Ron

    2016-05-01

    In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized. PMID:27151635

  12. Monoallelic Expression of Olfactory Receptors

    PubMed Central

    Monahan, Kevin; Lomvardas, Stavros

    2016-01-01

    The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron’s odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture. PMID:26359778

  13. Carnosine, nerve growth factor receptor and tyrosine hydroxylase expression during the ontogeny of the rat olfactory system.

    PubMed

    Biffo, S; Martí, E; Fasolo, A

    1992-01-01

    The localizations of carnosine, nerve growth factor (NGF) receptor and tyrosine hydroxylase (TH) were studied in the embryonic and postnatal rat olfactory bulb and epithelium by means of single- and double-immunostaining methods. Tyrosine hydroxylase ontogeny was also evaluated at the mRNA level by in situ hybridization. All these molecules were expressed in the olfactory bulb but with different developmental patterns and cellular localization: carnosine immunoreactivity is seen from embryonic day 17 in primary olfactory neurons scattered in the nasal cavity and in fibres projecting from them to the olfactory bulb. Nerve growth factor-receptor immunoreactivity associated with small glial-like cells is visible in some glomeruli starting from the second day of postnatal life. At postnatal day 10 NGF-receptor immunoreactivity is extended to all glomeruli. Periglomerular neurons expressing TH mRNA and protein are present prenatally and their number sharply increases during the early postnatal development. Double-staining methods show that TH and NGF-receptor immunoreactivity do not overlap in cell bodies and processes. In addition, NGF-receptor immunoreactivity is not colocalized with carnosine. These findings definitely exclude NGF-receptor expression in periglomerular and primary olfactory neurons, suggesting that at least part of NGF-receptor expression in the olfactory bulb is associated with glial cells. In addition, they provide the first immunohistochemical data on carnosine ontogeny and confirm at the mRNA level previous studies on the ontogeny of TH protein. PMID:1376608

  14. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    SciTech Connect

    Clewell, H.J. Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  15. A population of glomerular glutamatergic neurons controls sensory information transfer in the mouse olfactory bulb

    PubMed Central

    Tatti, Roberta; Seal, Rebecca P.; Edwards, Robert H.; Rodriguez, Ivan; Carleton, Alan

    2014-01-01

    In sensory systems, peripheral organs convey sensory inputs to relay networks where information is shaped by local microcircuits before being transmitted to cortical areas. In the olfactory system, odorants evoke specific patterns of sensory neuron activity which are transmitted to output neurons in olfactory bulb glomeruli. How sensory information is transferred and shaped at this level remains still unclear. Here we employ mouse genetics, 2-photon microscopy, electrophysiology and optogenetics, to identify a novel population of glutamatergic neurons (VGLUT3+) in the glomerular layer of the adult mouse olfactory bulb as well as several of their synaptic targets. Both peripheral and serotoninergic inputs control VGLUT3+ neurons firing. Furthermore, we show that VGLUT3+ neurons photostimulation in vivo strongly suppresses both spontaneous and odor-evoked firing of bulbar output neurons. In conclusion, we identify and characterize here a microcircuit controlling the transfer of sensory information at an early stage of the olfactory pathway. PMID:24804702

  16. Rapid and continuous activity-dependent plasticity of olfactory sensory input

    PubMed Central

    Cheetham, Claire E. J.; Park, Una; Belluscio, Leonardo

    2016-01-01

    Incorporation of new neurons enables plasticity and repair of circuits in the adult brain. Adult neurogenesis is a key feature of the mammalian olfactory system, with new olfactory sensory neurons (OSNs) wiring into highly organized olfactory bulb (OB) circuits throughout life. However, neither when new postnatally generated OSNs first form synapses nor whether OSNs retain the capacity for synaptogenesis once mature, is known. Therefore, how integration of adult-born OSNs may contribute to lifelong OB plasticity is unclear. Here, we use a combination of electron microscopy, optogenetic activation and in vivo time-lapse imaging to show that newly generated OSNs form highly dynamic synapses and are capable of eliciting robust stimulus-locked firing of neurons in the mouse OB. Furthermore, we demonstrate that mature OSN axons undergo continuous activity-dependent synaptic remodelling that persists into adulthood. OSN synaptogenesis, therefore, provides a sustained potential for OB plasticity and repair that is much faster than OSN replacement alone. PMID:26898529

  17. Primary adenocarcinoma of pigmented ciliary epithelium in a phthisical eye.

    PubMed

    Kumar, Jaya B; Proia, Alan D; Mruthyunjaya, Prithvi; Sharma, Sumit

    2016-01-01

    We report a case of adenocarcinoma of the pigmented ciliary epithelium arising in a phthisical eye. A 92-year-old man who initially presented with severe ocular pain had calcification extending from the posterior pole to ciliary body on B-scan ultrasonography to a degree not previously reported. We highlight the importance of screening for intraocular neoplasms in adults with a long-standing phthisical eye. PMID:26597037

  18. Olfactory dysfunction in Alzheimer’s disease

    PubMed Central

    Zou, Yong-ming; Lu, Da; Liu, Li-ping; Zhang, Hui-hong; Zhou, Yu-ying

    2016-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  19. Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis.

    PubMed

    Hanchate, Naresh K; Kondoh, Kunio; Lu, Zhonghua; Kuang, Donghui; Ye, Xiaolan; Qiu, Xiaojie; Pachter, Lior; Trapnell, Cole; Buck, Linda B

    2015-12-01

    The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules. PMID:26541607

  20. Ion transporter NKCC1, modulator of neurogenesis in murine olfactory neurons.

    PubMed

    Haering, Claudia; Kanageswaran, Ninthujah; Bouvain, Pascal; Scholz, Paul; Altmüller, Janine; Becker, Christian; Gisselmann, Günter; Wäring-Bischof, Janine; Hatt, Hanns

    2015-04-10

    Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. Here, we present electro-olfactogram recordings (EOG) demonstrating that NKCC1-deficient mice exhibit significant defects in perception of a complex odorant mixture (Henkel100) in both air-phase and submerged approaches. Using next generation sequencing (NGS) and RT-PCR experiments of NKCC1-deficient and wild type mouse transcriptomes, we confirmed the absence of a highly expressed ion transporter that could compensate for NKCC1. Additional histological investigations demonstrated a reduced number of cells in the olfactory epithelium (OE), resulting in a thinner neuronal layer. Therefore, we conclude that NKCC1 is an important transporter involved in chloride ion accumulation in the olfactory epithelium, but it is also involved in OSN neurogenesis. PMID:25713142

  1. Olfactory exploration: State of the art.

    PubMed

    Nguyen, D T; Rumeau, C; Gallet, P; Jankowski, R

    2016-04-01

    Olfactory disorders are fairly common in the general population. Exploration, on the other hand, is seldom performed by ENT specialists, even in reference centers. There may be three reasons for this: this particular sensory modality may seem unimportant to patients and/or physicians; available treatments may be underestimated, although admittedly much yet remains to be done; and olfactory exploration is not covered by the national health insurance scheme in France. Advances in research in recent decades have shed light on olfactory system functioning. At the same time, several techniques have been developed to allow maximally objective olfactory assessment, as olfactory disorder is sometimes the first sign of neurodegenerative pathology. Moreover, objective olfactory assessment may be needed in a medico-legal context. The present paper updates the techniques currently available for olfactory exploration. PMID:26384780

  2. Origin and endpoint of the olfactory nerve fibers: as described by Santiago Ramón y Cajal.

    PubMed

    Levine, Catherine; Marcillo, Alexander

    2008-07-01

    In the late Nineteenth Century, Santiago Ramón y Cajal was able to reproduce an exceptional illustration of the Olfactory Nerve pathway and its myriad of cells, by using the Golgi Method. Dr. Cajal focused intense study on the histology of the nervous system and published a treatise on the olfactory nerve fibers and the distinct peripheral origin and central nervous system endpoint of this unique pathway. The original title of this work is "Origen y terminación de las fibras nerviosas olfatorias" published in 1890. As the original publication is in Spanish, here we provide an English translation allowing present-day English speakers to read these writings. Cajal followed the trajectory of the olfactory nerve fibers as they transitioned between the peripheral and central nervous system and was able to assert that these fibers were not continuous from the olfactory bulb to the bipolar cells that relinquish into the olfactory epithelium, but that the olfactory system was made up of various cell types each having distinct morphologies and functions. This may very well be the first definitive description of the olfactory receptor neurons and the first illustrations of the continuity of these cells throughout the olfactory pathway. These meticulous histological preparations were created by first using Camillo Golgi's potassium dichromate and silver nitrate impregnation method known as "reazione nera" or "black reaction," where nerve cells, nerve fibers, and neuroglia could be visualized. This study exhibits the structural and functional organization of the mammalian fila olfactoria as it was investigated in centuries past. PMID:18383279

  3. The olfactory receptor family album

    PubMed Central

    Crasto, Chiquito; Singer, Michael S; Shepherd, Gordon M

    2001-01-01

    Analysis of the human genome draft sequences has revealed a more complete portrait of the olfactory receptor gene repertoire in humans than was available previously. The new information provides a basis for deeper analysis of the functions of the receptors, and promises new insights into the evolutionary history of the family. PMID:11597337

  4. Olfactory adventures of elephantine pheromones.

    PubMed

    Rasmussen, L E; Lazar, J; Greenwood, D R

    2003-02-01

    Understanding the linkage between behaviour of mammals in their natural environment and the molecular basis of their sensory modalities presents challenges to biologists. Our olfactory investigations that involve the largest extant land mammal, the elephant, offer some clues of how these events mesh in sequence. Proboscideans have developed a sophisticatedly organized society and they rank with primates and cetaceans with respect to cognitive abilities. Our studies of discrete, quantifiable pheromone-elicited behaviours demonstrate that Asian elephants utilize their olfactory senses during fundamental, life-strategy decisions, including mate choice, female bonding and male hierarchical sorting. How biologically relevant odorants traverse mucous interfaces to interact with cognate odorant receptors remains a basic question in vertebrate olfaction. We have partially tracked the molecular odour reception trail of behaviourally distinct pheromones, ( Z )-7-dodecenyl acetate and frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane), using approaches developed for insect studies and taking advantage of the extensive, highly mucoidal olfactory and vomeronasal systems that permit detailed investigations of pheromone-binding proteins. We have combined studies of quantifiable responses and behaviours with biochemical and biophysical investigations of the properties of protein-ligand complexes, their sequential pathways and associated protein-ligand fluxes. In the delineation of these sequential integrations of behavioural, biochemical and molecular events, we have discovered novel spatial and temporal adaptations in both the main olfactory and vomeronasal systems. PMID:12546671

  5. Olfactory Classical Conditioning in Neonates

    PubMed Central

    Sullivan, Regina M.; Taborsky-Barba, Suzanne; Mendoza, Raffael; Itano, Alison; Leon, Michael; Cotman, Carl W.; Payne, Terrence F.; Lott, Ira

    2007-01-01

    One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants’ training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared. PMID:2011429

  6. Olfactory assessment using the NIH Toolbox.

    PubMed

    Dalton, Pamela; Doty, Richard L; Murphy, Claire; Frank, Robert; Hoffman, Howard J; Maute, Christopher; Kallen, Michael A; Slotkin, Jerry

    2013-03-12

    The human olfactory system provides us with information about our environment that is critical to our physical and psychological well-being. Individuals can vary widely in their ability to detect, recognize, and identify odors, but still be within the range of normal function. Although several standardized tests of odor identification are available, few specifically address the issues in testing very young children, most of whom are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select among choices. Based on the format of the San Diego Odor Identification Test and the delivery system of the University of Pennsylvania Smell Identification Test, we developed 2 versions of an odor identification test using standardized odor stimuli in a scratch-and-sniff format in which participants match 5 (children) or 9 (adults) odors to pictures representing the odor source. Results from normative testing and validation showed that for most participants, the test could be completed in 5 minutes or less and that the poorer performance among the youngest children and the elderly was consistent with data from tests with larger numbers of items. Expanding on the pediatric version of the test with adult-specific and public health-relevant odors increased the ecological validity of the test and facilitated comparisons of intraindividual performance across developmental stages. PMID:23479541

  7. Olfactory assessment using the NIH Toolbox

    PubMed Central

    Doty, Richard L.; Murphy, Claire; Frank, Robert; Hoffman, Howard J.; Maute, Christopher; Kallen, Michael A.; Slotkin, Jerry

    2013-01-01

    The human olfactory system provides us with information about our environment that is critical to our physical and psychological well-being. Individuals can vary widely in their ability to detect, recognize, and identify odors, but still be within the range of normal function. Although several standardized tests of odor identification are available, few specifically address the issues in testing very young children, most of whom are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select among choices. Based on the format of the San Diego Odor Identification Test and the delivery system of the University of Pennsylvania Smell Identification Test, we developed 2 versions of an odor identification test using standardized odor stimuli in a scratch-and-sniff format in which participants match 5 (children) or 9 (adults) odors to pictures representing the odor source. Results from normative testing and validation showed that for most participants, the test could be completed in 5 minutes or less and that the poorer performance among the youngest children and the elderly was consistent with data from tests with larger numbers of items. Expanding on the pediatric version of the test with adult-specific and public health–relevant odors increased the ecological validity of the test and facilitated comparisons of intraindividual performance across developmental stages. PMID:23479541

  8. Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib

    PubMed Central

    Wang, Lizhi; Ding, Yan; Wei, Lai; Zhao, Dewei; Wang, Ruoyu; Zhang, Yuewei; Gu, Xuesong; Wang, Zhiqiang

    2016-01-01

    Abstract Olfactory neuroblastoma (ONB) is a rare cancer originating in the olfactory epithelium of the nasal vault. The recurrence rate of ONB is high, as the standard treatment of surgery followed by radiotherapy and/or chemotherapy is usually unsuccessful. The use of targeted therapy based on individual genomic variations after cancer relapse has not been reported. Here, we present the case of a 44-year-old man who was diagnosed with recurrent ONB and treated with a regimen developed using whole exome sequencing. Potential targets were first identified and then matched to appropriate drugs. Gene mutations in the genes encoding EGFR, FGFR2, KDR, and RET were discovered in the patient's tumor tissue by whole exome sequencing and the patient was treated with a combination of the targeted drugs cetuximab and sunitinib. Five days after treatment, enhancement magnetic resonance imaging showed a 65% reduction in tumor size, and the Visual analog scale headache scores went down to 2/10 from 10/10. Repeat imaging at 1 month showed a complete response. This study represents the first demonstration of an effective personalized treatment of ONB by targeted drugs, and sheds light on how precision medicine can be used to treat recurrent ONB that fails to respond to routine tumor resection, radiotherapy, and/or chemotherapy. PMID:27149458

  9. Functional morphology of the olfactory organ of the tongue sole, Cynoglossus semilaevis

    NASA Astrophysics Data System (ADS)

    Ma, Aijun; Wang, Xin'an

    2010-03-01

    The morphology and structure of the olfactory organ of Cynoglossus semilaevis Günther are described. The oval olfactory sacs on both sides differ in size and in the number of lamellae, with those on the abocular side having smaller sacs and fewer lamellae than those on the ocular side. On the ocular side, the average ratio of sac length to eye diameter is 2.1 (i.e.>1) with an average of 91 lamellae, while on the abocular side, the values were 1.7 (i.e.>1) and 69, respectively. In addition, the surface morphology varies in different parts of the lamella. The frontal part, near the anterior nostril, is a non-sensory margin with cilia-free epidermal cells. Within this is an internal ciliated sensory area, which is intercalated with ciliated receptor cells and a few ciliated non-sensory cells. Additionally, some dense ciliated non-sensory cells make up a non-sensory area, which also contains cilia-free epidermal cells distributed in patches. In the rear of the olfactory sac near the posterior nostril, the lamellae differ in morphology from those of the frontal olfactory sac but are similar in having few ciliated receptor cells. In other words, the surface of the lamellae in the rear part of the olfactory sac is mainly non-sensory. At present, four types of lamellae (I, II, III and IV) have been recognized in relation to the pattern of the sensory epithelium. In this study, the frontal and rear lamellae resembled types I and IV, respectively, but are referred to as types I' and IV' because they are slightly less developed. Data on the ratio of length of lamellae to eye diameter, number of lamellae and the type of surface pattern of the lamellae show that the development of the olfactory system of C. semilaevis facilitates prey capture.

  10. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  11. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    PubMed

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. PMID:27189720

  12. Modulation of spontaneous and odorant-evoked activity of rat olfactory sensory neurons by two anorectic peptides, insulin and leptin.

    PubMed

    Savigner, Agnès; Duchamp-Viret, Patricia; Grosmaitre, Xavier; Chaput, Michel; Garcia, Samuel; Ma, Minghong; Palouzier-Paulignan, Brigitte

    2009-06-01

    In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by approximately 25% and decreased the interspike intervals by approximately 13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status. PMID:19297511

  13. Modulation of Spontaneous and Odorant-Evoked Activity of Rat Olfactory Sensory Neurons by Two Anorectic Peptides, Insulin and Leptin

    PubMed Central

    Savigner, Agnès; Duchamp-Viret, Patricia; Grosmaitre, Xavier; Chaput, Michel; Garcia, Samuel; Ma, Minghong; Palouzier-Paulignan, Brigitte

    2009-01-01

    In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by ∼25% and decreased the interspike intervals by ∼13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status. PMID:19297511

  14. Angiotensinergic involvement in olfactory function

    SciTech Connect

    Speth, R.C.; Parker, J.L.; Wright, J.W.; Harding, J.W.

    1986-03-05

    The olfactory bulbs (OB) from Sprague-Dawley and Wistar-Kyoto rats were frozen and sectioned in a sagittal plane, 20 ..mu.. thick. Sections incubated with /sup 125/-Sar/sup 1/, Ile/sup 8/-AII indicated a high density of AII receptor binding sites in the external layers of the OB. Since the primary olfactory neurons synapse with the mitral cells in these layers, this suggests that AII may affect olfactory input to the OB. To test this hypothesis, male Sprague-Dawley rats, 9-12 weeks of age, n = 8, were administered 0.2 ml of 0.17 M ZnSO/sub 4/ into each nostril to lesion the primary olfactory neurons and their axon terminals in the OB. Rats treated with ZnSO/sub 4/ showed an impairment in their ability to find a buried food pellet, P = 0.041, Mann-Whitney test. Nine days post-treatment, the rats were sacrificed and AII receptors binding in homogenates of the OB was determined. There was a 23% increase (P < 0.05) in AII receptor density in the ZnSO/sub 4/ treated rat OB; it was correlated with the extent of the olfactory deficit, r/sub s/ = .91, Spearman Rank Order Test, P < .01. However, there was a 24% decrease in OB weight in the ZnSO/sub 4/ group, so the number of AII receptors per OB was unchanged. These data suggest that AII plays a role in olfaction. Localizing AII receptor changes within the OB by quantitative autoradiography will characterize the changes in AII receptor density caused by ZnSO/sub 4/.

  15. Evidence for functional asymmetry in the olfactory system of the Senegalese sole (Solea senegalensis).

    PubMed

    Velez, Zélia; Hubbard, Peter C; Barata, Eduardo N; Canário, Adelino V M

    2005-01-01

    The two olfactory epithelia of flatfish of the family Soleidae are essentially in contact with two distinct environments; the upper (right) side samples open water while the lower (left) side samples interstitial water. This study assessed whether there are differences in the responsiveness of the two epithelia by use of the electro-olfactogram in the Senegalese sole (Solea senegalensis). The upper epithelium was significantly more responsive to the basic amino acids (L-lysine and L-arginine), glycine, and L-threonine than the lower epithelium. The lower epithelium was significantly more responsive to aromatic amino acids (L-tryptophan, L-tyrosine, L-DOPA, and L-phenylalanine), L-leucine, and L-asparagine than the upper. Both epithelia had similar responsiveness to the sulphur-containing amino acids (L-cysteine and L-methionine), L-alanine, L-serine, and L-glutamine. Neither side was responsive to the acidic amino acids (L-aspartate and L-glutamate) or the D-isomers of any amino acid tested. The upper olfactory organ was much more responsive to conspecific-derived stimuli (bile and intestinal fluid) than the lower organ. We suggest that these differences in responsiveness may be related to different functional roles of the upper and lower epithelia in feeding and chemical communication. PMID:16059846

  16. 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

  17. Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes.

    PubMed

    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

  18. Olfactory Ensheathing Cells Express α7 Integrin to Mediate Their Migration on Laminin

    PubMed Central

    Ingram, Norianne T.; Khankan, Rana R.; Phelps, Patricia E.

    2016-01-01

    The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo. PMID:27078717

  19. Olfactory Ensheathing Cells Express α7 Integrin to Mediate Their Migration on Laminin.

    PubMed

    Ingram, Norianne T; Khankan, Rana R; Phelps, Patricia E

    2016-01-01

    The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo. PMID:27078717

  20. Is the age-related loss in olfactory sensitivity similar for light and heavy molecules?

    PubMed

    Sinding, Charlotte; Puschmann, Laura; Hummel, Thomas

    2014-06-01

    The process of aging affects olfaction quite early and can lead to a major handicap. One may ask whether olfactory loss is general or if it affects some odors more specifically? We investigated whether an age-related increase in olfactory threshold could be more or less specific to heavy or light molecules, based on the idea that these odors would bind differently to olfactory receptors. One group of 30 older subjects (50-70 years) and one group of 30 young adults (18-30 years) were tested for their threshold to 4 odors. Two odorants were light molecules (<150 g/mol) and the 2 others were heavy molecules (>150 g/mol). Both sets contained a single molecule and a binary mixture. Older subjects performed worse than young adults in an odor identification task, confirming a decline in the olfactory function. As a major result, young adults were as sensitive to light and heavy molecules; on the contrary, older subjects were less sensitive to heavy molecules (single molecule and binary mixture). The results suggest that older people present a heterogeneous olfactory loss more specific to heavier molecules. PMID:24803088

  1. Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

    SciTech Connect

    Wang, Lu; Gallagher, Evan P.

    2013-01-15

    Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

  2. Expression of G proteins in the olfactory receptor neurons of the newt Cynops pyrrhogaster: their unique projection into the olfactory bulbs.

    PubMed

    Nakada, Tomoaki; Hagino-Yamagishi, Kimiko; Nakanishi, Koki; Yokosuka, Makoto; Saito, Toru R; Toyoda, Fumiyo; Hasunuma, Itaru; Nakakura, Takashi; Kikuyama, Sakae

    2014-10-15

    We analyzed the expression of G protein α subunits and the axonal projection into the brain in the olfactory system of the semiaquatic newt Cynops pyrrhogaster by immunostaining with antibodies against Gαolf and Gαo , by in situ hybridization using probes for Gαolf , Gαo , and Gαi2 , and by neuronal tracing with DiI and DiA. The main olfactory epithelium (OE) consists of two parts, the ventral OE and dorsal OE. In the ventral OE, the Gαolf - and Gαo -expressing neurons are located in the apical and basal zone of the OE, respectively. This zonal expression was similar to that of the OE in the middle cavity of the fully aquatic toad Xenopus laevis. However, the Gαolf - and Gαo -expressing neurons in the newt ventral OE project their axons toward the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), respectively, whereas in Xenopus, the axons of both neurons project solely toward the MOB. In the dorsal OE of the newt, as in the principal cavity of Xenopus, the majority of the neurons express Gαolf and extend their axons into the MOB. In the vomeronasal organ (VNO), the neurons mostly express Gαo . These neurons and quite a few Gαolf -expressing neurons project their axons toward the AOB. This feature is similar to that in the terrestrial toad Bufo japonicus and is different from that in Xenopus, in which VNO neurons express solely Gαo , although their axons invariably project toward the AOB. We discuss the findings in the light of diversification and evolution of the vertebrate olfactory system. PMID:24771457

  3. Olfactory abnormalities in temporal lobe epilepsy.

    PubMed

    Desai, M; Agadi, J B; Karthik, N; Praveenkumar, S; Netto, A B

    2015-10-01

    We studied olfactory function in a cohort of 25 temporal lobe epilepsy (TLE) patients and 25 healthy controls. Our objectives were to measure olfactory acuity in patients with right, left or bilateral TLE and compare them with age and sex matched controls, and to correlate olfactory acuity with duration of seizure, baseline seizure control and the number of drugs used. Olfactory impairment is common in neurological disorders and dysfunction of the temporo-limbic neural substrates involved in olfactory perception is noted in TLE. We measured olfactory acuity in 25 patients with TLE, nine with right, 10 with left and six with bilateral temporal lobe seizure activity, and compared them to the controls. Odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) which is a 40 item olfactory test used to diagnose olfactory deficits. Our results showed that patients with TLE exhibited significant impairment in UPSIT performance compared to the controls. There was no significant difference in scores between the right and left TLE patients. The severity of olfactory impairment did not correlate with the duration of seizures, baseline seizure control and number of drugs used. We concluded that significant olfactory impairment is seen in both right and left TLE patients, unrelated to the duration and baseline frequency of seizures or drugs used. PMID:26149406

  4. 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

  5. Enhancement of odorant-induced responses in olfactory receptor neurons by zinc nanoparticles.

    PubMed

    Viswaprakash, Nilmini; Dennis, John C; Globa, Ludmila; Pustovyy, Oleg; Josephson, Eleanor M; Kanju, Patrick; Morrison, Edward E; Vodyanoy, Vitaly J

    2009-09-01

    Zinc metal nanoparticles in picomolar concentrations strongly enhance odorant responses of olfactory sensory neurons. One- to 2-nm metallic particles contain 40-300 zinc metal atoms, which are not in an ionic state. We exposed rat olfactory epithelium to metal nanoparticles and measured odorant responses by electroolfactogram and whole-cell patch clamp. A small amount of zinc nanoparticles added to an odorant or an extracellular/intracellular particle perfusion strongly increases the odorant response in a dose-dependent manner. Zinc nanoparticles alone produce no odor effects. Copper, gold, or silver nanoparticles do not produce effects similar to those of zinc. If zinc nanoparticles are replaced by Zn(+2) ions in the same concentration range, we observed a reduction of the olfactory receptor neuron odorant response. Based on these observations, we hypothesize that zinc nanoparticles are closely located to the interface between the guanine nucleotide-binding protein and the receptor proteins and are involved in transferring signals in the initial events of olfaction. Our results suggest that zinc metal nanoparticles can be used to enhance and sustain the initial olfactory events. PMID:19525316

  6. Evaluation of the toxicity of zinc in the rat olfactory neuronal cell line, Odora.

    PubMed

    Hsieh, H; Amlal, H; Genter, M B

    2015-03-01

    Zinc (Zn) has long been touted as a panacea for common cold. Recently, there has been some controversy over whether an intranasal (IN) zinc gluconate gel, purported to fight colds, causes anosmia, or loss of the sense of smell, in humans. Previous evidence has shown that IN zinc sulfate (ZnSO4) solutions can cause anosmia in humans as well as significant damage to the olfactory epithelium in rodents. Using an in vitro olfactory neuron model (the rat Odora cell line), we tested the hypothesis that Zn toxicity was caused by inhibition of the hydrogen voltage-gated channel 1(HVCN1), leading to acidosis and apoptotic cell death. Following studies to characterize the toxicity of zinc gluconate and ZnSO4, Odora cells were grown on coverslips and loaded with 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester to measure intracellular pH in the presence and absence of Zn salts. While we found that HVCN1 is not functional in Odora cells, we found that olfactory neurons in vitro maintain their intracellular pH through a sodium/proton exchanger, specifically the sodium proton antiporter 1. ZnSO4, at nontoxic levels, had no impact on intracellular pH after acute exposure or after 24 h of incubation with the cells. In conclusion, Zn toxicity is not mediated through an acidification of intracellular pH in olfactory neurons in vitro. PMID:24980442

  7. Innate Predator Odor Aversion Driven by Parallel Olfactory Subsystems that Converge in the Ventromedial Hypothalamus.

    PubMed

    Pérez-Gómez, Anabel; Bleymehl, Katherin; Stein, Benjamin; Pyrski, Martina; Birnbaumer, Lutz; Munger, Steven D; Leinders-Zufall, Trese; Zufall, Frank; Chamero, Pablo

    2015-05-18

    The existence of innate predator aversion evoked by predator-derived chemostimuli called kairomones offers a strong selective advantage for potential prey animals. However, it is unclear how chemically diverse kairomones can elicit similar avoidance behaviors. Using a combination of behavioral analyses and single-cell Ca(2+) imaging in wild-type and gene-targeted mice, we show that innate predator-evoked avoidance is driven by parallel, non-redundant processing of volatile and nonvolatile kairomones through the activation of multiple olfactory subsystems including the Grueneberg ganglion, the vomeronasal organ, and chemosensory neurons within the main olfactory epithelium. Perturbation of chemosensory responses in specific subsystems through disruption of genes encoding key sensory transduction proteins (Cnga3, Gnao1) or by surgical axotomy abolished avoidance behaviors and/or cellular Ca(2+) responses to different predator odors. Stimulation of these different subsystems resulted in the activation of widely distributed target regions in the olfactory bulb, as assessed by c-Fos expression. However, in each case, this c-Fos increase was observed within the same subnuclei of the medial amygdala and ventromedial hypothalamus, regions implicated in fear, anxiety, and defensive behaviors. Thus, the mammalian olfactory system has evolved multiple, parallel mechanisms for kairomone detection that converge in the brain to facilitate a common behavioral response. Our findings provide significant insights into the genetic substrates and circuit logic of predator-driven innate aversion and may serve as a valuable model for studying instinctive fear and human emotional and panic disorders. PMID:25936549

  8. Adenylate cyclase mediates olfactory transduction for a wide variety of odorants.

    PubMed Central

    Lowe, G; Nakamura, T; Gold, G H

    1989-01-01

    An odor-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] is thought to mediate olfactory transduction in vertebrates. However, it is not known whether the adenylate cyclase serves this function for all odorants or for only certain classes of odorants. To investigate this question, we have compared the abilities of 35 odorants to stimulate the adenylate cyclase and to elicit an electrophysiological response. We report a strong positive correlation between the magnitude of adenylate cyclase stimulation and the summated electrical response of the olfactory epithelium (electro-olfactogram) evoked by individual odorants. We also show that the adenylate cyclase stimulator forskolin equally attenuates the electro-olfactogram response for all odorants tested. These data provide evidence that the adenylate cyclase mediates transduction for a wide variety of odorants. PMID:2787513

  9. 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

  10. Insight of scent: experimental evidence of olfactory capabilities in the wandering albatross (Diomedea exulans).

    PubMed

    Mardon, J; Nesterova, A P; Traugott, J; Saunders, S M; Bonadonna, F

    2010-02-15

    Wandering albatrosses routinely forage over thousands of kilometres of open ocean, but the sensory mechanisms used in the food search itself have not been completely elucidated. Recent telemetry studies show that some spatial behaviours of the species are consistent with the 'multimodal foraging strategy' hypothesis which proposes that birds use a combination of olfactory and visual cues while foraging at sea. The 'multimodal foraging strategy' hypothesis, however, still suffers from a lack of experimental evidence, particularly regarding the olfactory capabilities of wandering albatrosses. As an initial step to test the hypothesis, we carried out behavioural experiments exploring the sensory capabilities of adult wandering albatrosses at a breeding colony. Three two-choice tests were designed to investigate the birds' response to olfactory and visual stimuli, individually or in combination. Perception of the different stimuli was assessed by comparing the amount of exploration directed towards an 'experimental' display or a 'control' display. Our results indicate that birds were able to perceive the three types of stimulus presented: olfactory, visual and combined. Moreover, olfactory and visual cues were found to have additional effects on the exploratory behaviours of males. This simple experimental demonstration of reasonable olfactory capabilities in the wandering albatross supports the 'multimodal foraging strategy' and is consistent with recent hypotheses of the evolutionary history of procellariiforms. PMID:20118306

  11. Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit

    PubMed Central

    Ebrahim, Shimaa A. M.; Dweck, Hany K. M.; Stökl, Johannes; Hofferberth, John E.; Trona, Federica; Weniger, Kerstin; Rybak, Jürgen; Seki, Yoichi; Stensmyr, Marcus C.; Sachse, Silke; Hansson, Bill S.; Knaden, Markus

    2015-01-01

    Detecting danger is one of the foremost tasks for a neural system. Larval parasitoids constitute clear danger to Drosophila, as up to 80% of fly larvae become parasitized in nature. We show that Drosophila melanogaster larvae and adults avoid sites smelling of the main parasitoid enemies, Leptopilina wasps. This avoidance is mediated via a highly specific olfactory sensory neuron (OSN) type. While the larval OSN expresses the olfactory receptor Or49a and is tuned to the Leptopilina odor iridomyrmecin, the adult expresses both Or49a and Or85f and in addition detects the wasp odors actinidine and nepetalactol. The information is transferred via projection neurons to a specific part of the lateral horn known to be involved in mediating avoidance. Drosophila has thus developed a dedicated circuit to detect a life-threatening enemy based on the smell of its semiochemicals. Such an enemy-detecting olfactory circuit has earlier only been characterized in mice and nematodes. PMID:26674493

  12. Does iron deficiency anemia affect olfactory function?

    PubMed

    Dinc, Mehmet Emre; Dalgic, Abdullah; Ulusoy, Seckin; Dizdar, Denizhan; Develioglu, Omer; Topak, Murat

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values. PMID:26963317

  13. [Olfactory dysfunction : Update on diagnosis and treatment].

    PubMed

    Kühn, M; Abolmaali, N; Smitka, M; Podlesek, D; Hummel, T

    2016-07-01

    Olfactory dysfunction is a common disorder, particularly in elderly people. From the etiologic point of view, we distinguish between sinunasal and non-sinunasal causes of dysosmia. As an important early symptom of neurodegenerative disease, dysosmia is particularly relevant in the diagnosis of Parkinson's or Alzheimer's disease. In addition to complete ENT examination and olfactory testing, e.g., with "Sniffin' Sticks", modern imaging procedures, e. g. MRI, are becoming more and more important for diagnostics, prognosis, and treatment decisions. Olfactory testing in children needs to be adapted to their shorter concentration span and limited range of known olfactory stimuli. Depending on the etiology, olfactory training, antiphlogistic measures, and surgical procedures are most promising. In cases of intracranial causes of dysosmia, neurosurgeons should know and respect anatomic structures of the olfactory signal pathway, not least for long-term prognosis. PMID:27364339

  14. Mucus trail tracking in a predatory snail: olfactory processing retooled to serve a novel sensory modality

    PubMed Central

    Patel, Kinjal; Shaheen, Nagma; Witherspoon, Jessica; Robinson, Natallia; Harrington, Melissa A

    2014-01-01

    Introduction The rosy wolfsnail (Euglandina rosea), a predatory land snail, finds prey snails and potential mates by following their mucus trails. Euglandina have evolved unique, mobile lip extensions that detect mucus and aid in following trails. Currently, little is known of the neural substrates of the trail-following behavior. Methods To investigate the neural correlates of trail following we used tract-tracing experiments in which nerves were backfilled with either nickel-lysine or Lucifer yellow, extracellular recording of spiking neurons in snail procerebra using a multielectrode array, and behavioral assays of trail following and movement toward the source of a conditioned odor. Results The tract-tracing experiments demonstrate that in Euglandina, the nerves carrying mucus signals innervate the same region of the central ganglia as the olfactory nerves, while the electrophysiology studies show that mucus stimulation of the sensory epithelium on the lip extensions alters the frequency and pattern of neural activity in the procerebrum in a manner similar to odor stimulation of the olfactory epithelium on the optic tentacles of another land snail species, Cantareus aspersa (previously known as Helix aspersa). While Euglandina learn to follow trails of novel chemicals that they contact with their lip extensions in one to three trials, these snails proved remarkably resistant to associative learning in the olfactory modality. Even after seven to nine pairings of odorant molecules with food, they showed no orientation toward the conditioned odor. This is in marked contrast to Cantareus snails, which reliably oriented toward conditioned odors after two to three trials. Conclusions The apparent inability of Euglandina to learn to associate food with odors and use odor cues to drive behavior suggests that the capability for sophisticated neural processing of nonvolatile mucus cues detected by the lip extensions has evolved at the expense of processing of odorant

  15. Olfactory neuroblastoma: A case report

    PubMed Central

    USLU, GONCA HANEDAN; CANYILMAZ, EMINE; ZENGIN, AHMET YASAR; MUNGAN, SEVDEGUL; YONEY, ADNAN; BAHADIR, OSMAN; GOCMEZ, HUSEYIN

    2015-01-01

    Olfactory neuroblastoma (ON) is a rare type of malignant neoplasm originating from the olfactory neuroepithelial cells of the nasal cavity. ON is also known as esthesioneuroblastoma or neuroendocrine carcinoma. The malignancy accounts for <3% of tumors originating in the nasal cavity. Through the nasal cavity, ON may infiltrate the sinuses, the orbit and the cranium. The tumor is characterized by a pattern of slow growth and local recurrences. Treatment options are surgical excision or surgery combined with a radiotherapy (RT) and/or chemotherapy combination treatment. The present study reports the case of a 69-year-old patient with a mass in the nasal cavity who was treated by combined surgical excision and RT. The literature for ON and the treatment of the tumor are also discussed. PMID:26788185

  16. Role of Centrifugal Projections to the Olfactory Bulb in Olfactory Processing

    ERIC Educational Resources Information Center

    Kiselycznyk, Carly L.; Zhang, Steven; Linster, Christine

    2006-01-01

    While there is evidence that feedback projections from cortical and neuromodulatory structures to the olfactory bulb are crucial for maintaining the oscillatory dynamics of olfactory bulb processing, it is not clear how changes in dynamics are related to odor perception. Using electrical lesions of the olfactory peduncle, sparing output from the…

  17. [Subjective assessment of olfactory function].

    PubMed

    Evren, Cenk; Yiğit, Volkan Bilge; Çınar, Fikret

    2015-01-01

    Of the five senses, the sense of smell is the most complex and unique in structure and organization. As diagnostic and therapeutic modalities are often underdeveloped, the sense of smell has been inadequately studied. Olfactory disorders may result from benign pathologies such as sinusitis as well as several diseases including Parkinson's disease, temporal lobe epilepsy, schizophrenia and Alzheimer disease. In this article, we aim to instruct the otorhinolaryngology specialists and residents regarding the tests which measure odor subjectively. PMID:25934410

  18. [Olfactory disorders – history, classification and implications].

    PubMed

    Welge-Lüssen, Antje

    2016-01-01

    Smell disorders are common and can be found in 3 – 5 % of the population under 65 years. With growing age these numbers increase up to 50 % and more. Qualitative disorders which cannot be measured are differentiated from quantitative disorders. Self-assessment of olfactory function is rather poor therefore olfactory testing is mandatory in cases of patients complaining about an olfactory disorder. Olfactory screening smell tests are available for orientation, however, for detailed testing or in cases of a pathological screening test an extensive psychophysical olfactory test battery such as the Sniffin' Sticks Test battery should be used. According to the result of the test battery olfactory function can be qualified as norm, hyp- or anosmic. Additionally, in cases of medicolegal questions, olfactory evoked potentials can be recorded. Smell disorders are classified according to the history, clinical and endoscopic examination of the nose. Imaging techniques such as magnetic resonance imaging (MRI) or computertomography may contribute to classify the disorder. Sinunasal olfactory disorders are considered to be the most common ones. If the etiology remains unclear a neurological examination has to be performed in order to rule out a concomitant neurodegenerative disease. Olfactory disorders in the elderly might have to be considered as a sign of a reduced regeneration capacity in general being depicted in an increase in overall mortality in affected subjects. PMID:27132644

  19. 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

  20. Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans

    PubMed Central

    Wallrabenstein, Ivonne; Singer, Marco; Panten, Johannes; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    In mice, trace amine-associated receptors (TAARs) are interspersed in the olfactory epithelium and constitute a chemosensory subsystem that is highly specific for detecting volatile amines. Humans possess six putative functional TAAR genes. Human TAAR5 (hTAAR5) is highly expressed in the olfactory mucosa and was shown to be specifically activated by trimethylamine. In this study, we were challenged to uncover an effective blocker substance for trimethylamine-induced hTAAR5 activation. To monitor blocking effects, we recombinantly expressed hTAAR5 and employed a commonly used Cre-luciferase reporter gene assay. Among all tested potential blocker substances, Timberol®, an amber-woody fragrance, is able to inhibit the trimethylamine-induced hTAAR5 activation up to 96%. Moreover, human psychophysical data showed that the presence of Timberol® increases the olfactory detection threshold for the characteristic fishy odor of trimethylamine by almost one order of magnitude. In conclusion, our results show that among tested receptors Timberol® is a specific and potent antagonist for the hTAAR5-mediated response to trimethylamine in a heterologous system. Furthermore, our data concerning the observed shift of the olfactory detection threshold in vivo implicate that hTAAR5 or other receptors that may be inhibited by Timberol® could be involved in the high affinity olfactory perception of trimethylamine in humans. PMID:26684881

  1. Sleep and olfactory cortical plasticity

    PubMed Central

    Barnes, Dylan C.; Wilson, Donald A.

    2014-01-01

    In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders. PMID:24795585

  2. Recording Temperature-induced Neuronal Activity through Monitoring Calcium Changes in the Olfactory Bulb of Xenopus laevis

    PubMed Central

    Kludt, Eugen; Schild, Detlev

    2016-01-01

    The olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. However, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. Premetamorphic Xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. These characteristics make them well suited for studying olfaction, and particularly thermosensitivity. The present article describes the complete procedure for measuring temperature responses in the olfactory bulb of X. laevis larvae. Firstly, the electroporation of olfactory receptor neurons (ORNs) is performed with spectrally distinct dyes loaded into the nasal cavities in order to stain their axon terminals in the bulbar neuropil. The differential staining between left and right receptor neurons serves to identify the γ-glomerulus as the only structure innervated by contralateral presynaptic afferents. Secondly, the electroporation is combined with focal bolus loading in the olfactory bulb in order to stain mitral cells and their dendrites. The 3D brain volume is then scanned under line-illumination microscopy for the acquisition of fast calcium imaging data while small temperature drops are induced at the olfactory epithelium. Lastly, the post-acquisition analysis allows the morphological reconstruction of the thermosensitive network comprising the γ-glomerulus and its innervating mitral cells, based on specific temperature-induced Ca2+ traces. Using chemical odorants as stimuli in addition to temperature jumps enables the comparison between thermosensitive and chemosensitive networks in the olfactory bulb. PMID:27286501

  3. Recording Temperature-induced Neuronal Activity through Monitoring Calcium Changes in the Olfactory Bulb of Xenopus laevis.

    PubMed

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

    2016-01-01

    The olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. However, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. Premetamorphic Xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. These characteristics make them well suited for studying olfaction, and particularly thermosensitivity. The present article describes the complete procedure for measuring temperature responses in the olfactory bulb of X. laevis larvae. Firstly, the electroporation of olfactory receptor neurons (ORNs) is performed with spectrally distinct dyes loaded into the nasal cavities in order to stain their axon terminals in the bulbar neuropil. The differential staining between left and right receptor neurons serves to identify the γ-glomerulus as the only structure innervated by contralateral presynaptic afferents. Secondly, the electroporation is combined with focal bolus loading in the olfactory bulb in order to stain mitral cells and their dendrites. The 3D brain volume is then scanned under line-illumination microscopy for the acquisition of fast calcium imaging data while small temperature drops are induced at the olfactory epithelium. Lastly, the post-acquisition analysis allows the morphological reconstruction of the thermosensitive network comprising the γ-glomerulus and its innervating mitral cells, based on specific temperature-induced Ca(2+) traces. Using chemical odorants as stimuli in addition to temperature jumps enables the comparison between thermosensitive and chemosensitive networks in the olfactory bulb. PMID:27286501

  4. THE DISTINCT TEMPORAL ORIGINS OF OLFACTORY BULB INTERNEURON SUBTYPES

    PubMed Central

    Batista-Brito, Renata; Close, Jennie; Machold, Robert; Ekker, Mark; Fishell, Gord

    2008-01-01

    Olfactory bulb (OB) interneurons are a heterogeneous population produced beginning in embryogenesis and continuing through adulthood. Understanding how this diversity arises will provide insight into how olfactory bulb microcircuitry is established as well as adult neurogenesis. Specific spatial domains have been shown to contribute specific interneuron subtypes. However, the temporal profile by which OB interneuron subtypes are produced is unknown. Using inducible genetic fate mapping of Dlx1/2 precursors, we analyzed the production of seven OB interneuron subtypes and find that the generation of each subpopulation has a unique temporal signature. Within the glomerular layer, while the production of TH-positive interneurons is maximal during early embryogenesis, it decreases thereafter. By contrast, the generation of CB interneurons is maximal during late embryogenesis and declines postnatally, while CR cell production is low during embryogenesis and increases postnatally. PV interneurons within the external plexiform layer are produced only perinatally, while the generation of 5T4-positive granule cells in the mitral cell layer does not change significantly over time. CR-positive granule cells are not produced at early embryonic timepoints, but constitute a large percentage of the granule cells born after birth. Blanes cells by contrast are produced in greatest number during embryogenesis. Taken together we provide the first comprehensive analysis of the temporal generation of olfactory bulb interneuron subtypes and demonstrate that the timing by which these populations are produced is tightly orchestrated. PMID:18400896

  5. Olfactory coding in five moth species from two families.

    PubMed

    Bisch-Knaden, Sonja; Carlsson, Mikael A; Sugimoto, Yuki; Schubert, Marco; Mißbach, Christine; Sachse, Silke; Hansson, Bill S

    2012-05-01

    The aim of the present study was to determine what impact phylogeny and life history might have on the coding of odours in the brain. Using three species of hawk moths (Sphingidae) and two species of owlet moths (Noctuidae), we visualized neural activity patterns in the antennal lobe, the first olfactory neuropil in insects, evoked by a set of ecologically relevant plant volatiles. Our results suggest that even between the two phylogenetically distant moth families, basic olfactory coding features are similar. But we also found different coding strategies in the moths' antennal lobe; namely, more specific patterns for chemically similar odorants in the two noctuid species than in the three sphingid species tested. This difference demonstrates the impact of the phylogenetic distance between species from different families despite some parallel life history traits found in both families. Furthermore, pronounced differences in larval and adult diet among the sphingids did not translate into differences in the olfactory code; instead, the three species had almost identical coding patterns. PMID:22496291

  6. 181 Olfactory Disfunctions in Patients with Chronic Rhinosinusitis

    PubMed Central

    Sánchez Vallecillo, María Victoria; Fraire, María Emilia; Baena-Cagnani, Carlos E.; Zernotti, Mario

    2012-01-01

    Background There are several factors that could produce olfactory dysfunction. The chronic inflammation of the upper air tract, especially allergic rhinitis is mentioned as a trigger factor. The aim of this study is assess the prevalence and identify clinical features associated with olfactory dysfunction in patients with chronic rhinosinusitis. Methods A prospective, analytical and observational study in adult patients (> 18 years) with chronic rhinosinusitis during the period May-October of 2010. We used the CCCRC (Connecticut Chemosensory Clinical Research Center smell test) Results A total of 33 patients were investigated. In the group of patients between 18 and 39 years, 73% of patients suffer from hyposmia and 18% anosmia; for the group of 40 to 64 years, 63% with hyposmia and 37% anosmia; patients older than 65 years, 67% hyposmia and 33% with anosmia. In the smokers group the 11% of patient presented hyposmia and 13% anosmia (P < 0.05); 5% in both cases had a history of nasal endoscopic surgery. In patients with chronic rhinosinusitis with nasal polyps have 18% with hyposmia and 19% with anosmia (P < 0.05). A 20% with allergic rhinitis had hyposmia while anosmia in 22% (P < 0.05). Septal deviation patients had 20% of hyposmia (P < 0.001) and 12% anosmia. Patients with turbinate hypertrophy had 22% hyposmia (P < 0.001) and 13% anosmia while in the group of patients with Asthma, the 4% had hyposmia and 16% anosmia (P < 0.001). Conclusions Nasal polyposis, septal deviation, turbinate hypertrophy, smoke, allergic rhinitis and asthma are negative predictors factors of olfactory dysfunction in patients with CRS. A previous endoscopic surgery, age and sex would not intervene in the olfactory loss.

  7. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning

    PubMed Central

    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.

    2010-01-01

    Summary Olfactory signals influence social interactions in a variety of species [1, 2]. 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 [1–5]. 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) [6–11] 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 (CS2), a component of rodent breath and a known social signal mediating the acquisition of STFPs [12–14]. Responses to sub-micromolar concentrations of CS2 in the main olfactory epithelium or in identified GC-D+ OSNs are absent in mice lacking CNGA3 or CAII and drastically reduced in mice lacking GC-D. Mice in which GC-D+ OSN transduction mechanisms have been disrupted fail to acquire STFPs from either live or surrogate demonstrator mice and do not exhibit neuronal activation of the ventral subiculum of the hippocampus, a brain region implicated in STFP retrieval [15]. Our findings indicate that GC-D+ OSNs detect chemosignals that facilitate food-related social interactions. PMID:20637621

  8. Facial, olfactory, and vocal cues to female reproductive value.

    PubMed

    Röder, Susanne; Fink, Bernhard; Jones, Benedict C

    2013-01-01

    Facial, olfactory, and vocal cues may advertise women's fertility. However, most of the evidence for this proposal has come from studies of changes in young adult women's attractiveness over the menstrual cycle. By contrast with this emphasis on changes in attractiveness over the menstrual cycle, possible changes in women's attractiveness over their lifespan have received little attention. The present study investigated men's ratings of young girls' (11-15 years old), adult women's (19-30 years old) and circum-menopausal women's (50-65 years old) facial, body odor, and vocal attractiveness and femininity. Faces and voices, but not body odors, of young girls and adult women were perceived to be significantly more attractive and feminine than those of circum-menopausal women. These data suggest that facial and vocal cues may be cues to women's reproductive value, but that body odor cues do not necessarily advertise this information. PMID:23728193

  9. Detection of explosives by olfactory sensory neurons.

    PubMed

    Corcelli, Angela; Lobasso, Simona; Lopalco, Patrizia; Dibattista, Michele; Araneda, Ricardo; Peterlin, Zita; Firestein, Stuart

    2010-03-15

    The response of olfactory sensory neurons to TNT and RDX as well as to some volatile organic compounds present in the vapors of antipersonnel landmines has been studied both in the pig and in the rat. GC/MS analyses of different plastic components of six different kinds of landmines were performed in order to identify the components of the "perfume" of mines. Studies on rat olfactory mucosa were carried out with electro-olfactogram and calcium imaging techniques, while changes in the cyclic adenosine monophosphate (cAMP) levels following exposure to odorants and explosives were used as a criterion to evaluate the interaction of TNT and RDX with olfactory receptors in a preparation of isolated pig olfactory cilia. These studies indicate that chemical compounds associated with explosives and explosive devices can activate mammalian olfactory receptors. PMID:19913995

  10. Olfactory Neuroblastoma: A Case Report.

    PubMed

    Olmo, Heather R; Stokes, Steven Marc; Foss, Robert D

    2016-06-01

    A 43-year-old female presented with persistent nasal congestion with intermittent epistaxis without resolution for the preceding 5 years. Clinical examination revealed a large pink rubbery mass, medial to the middle turbinate in the right nasal cavity extending to the choana. Radiographic images demonstrated a heterogeneously enhancing lobular soft tissue mass filling the right nasal cavity, causing lateral bowing of the right medial orbital wall and extending posteriorly to the right anterior ethmoid sinus. The clinical, radiographic, histologic, and immunohistochemical features of olfactory neuroblastoma are discussed. PMID:26316323

  11. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

    PubMed Central

    Bressel, Olaf Christian; Khan, Mona

    2015-01-01

    ABSTRACT Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene‐targeted strains of the OR‐IRES‐marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, “count every cell” strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain‐specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17‐fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene‐targeted strains. J. Comp. Neurol. 524:199–209, 2016. © 2015 Wiley Periodicals, Inc. PMID:26100963

  12. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb.

    PubMed

    Bressel, Olaf Christian; Khan, Mona; Mombaerts, Peter

    2016-01-01

    Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene-targeted strains of the OR-IRES-marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, "count every cell" strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain-specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17-fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene-targeted strains. PMID:26100963

  13. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device. (a) Identification. An olfactory test device is used to determine whether an olfactory loss is present. The device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Olfactory test device. 874.1600 Section...

  14. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device. (a) Identification. An olfactory test device is used to determine whether an olfactory loss is present. The device... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Olfactory test device. 874.1600 Section...

  15. 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.

  16. Age-related changes in p2 odorant receptor mapping in the olfactory bulb.

    PubMed

    Costanzo, Richard M; Kobayashi, Masayoshi

    2010-06-01

    The ability to identify odors is dependent on the spatial mapping of odorant receptors onto fixed positions within the olfactory bulb. In elderly adults, odor identification and discrimination is often impaired. The objective of this study was to determine if there are age-related changes in odorant receptor mapping. We studied 8 groups of mice ranging in age from 2 weeks to 2.5 years and mapped the projection of P2 odorant receptors onto targeted glomeruli within medial and lateral domains of the olfactory bulb. A total of 60 mice were used to measure the number of P2 glomeruli, bulb length, the position of each glomerulus, and the amount of P2 axons targeting each glomerulus. We found that over 70% of olfactory bulbs contained multiple P2 glomeruli, bulb length increased 42% between the ages of 2 and 13 weeks, and the position of P2 glomeruli shifted with bulb growth. In most cases, targeted glomeruli were either completely or partially filled with P2 axons. In some cases, targeting was diffuse, with glomeruli receiving only a few stray P2-labeled axons. The frequency of diffuse targeting was rare (<4%) in adult mice 3-6 months in age. However, significant increases in diffuse targeting were observed in older mice, reaching 10% at 1 year and 22% at 2 years of age. These findings suggest that odorant receptor mapping becomes more disrupted in old age and could account for impaired olfactory function in elderly adults. PMID:20231263

  17. Newborn Interneurons in the Accessory Olfactory Bulb Promote Mate Recognition in Female Mice

    PubMed Central

    Oboti, Livio; Schellino, Roberta; Giachino, Claudio; Chamero, Pablo; Pyrski, Martina; Leinders-Zufall, Trese; Zufall, Frank; Fasolo, Aldo; Peretto, Paolo

    2011-01-01

    In the olfactory bulb of adult rodents, local interneurons are constantly replaced by immature precursors derived from the subventricular zone. Whether any olfactory sensory process specifically relies on this cell renewal remains largely unclear. By using the well known model of mating-induced imprinting to avoid pregnancy block, which requires accessory olfactory bulb (AOB) function, we demonstrate that this olfactory memory formation critically depends on the presence of newborn granule neurons in this brain region. We show that, in adult female mice, exposure to the male urine compounds involved in mate recognition increases the number of new granule cells surviving in the AOB. This process is modulated by male signals sensed through the vomeronasal organ and, in turn, changes the activity of the downstream amygdaloid and hypothalamic nuclei involved in the pregnancy block response. Chemical depletion of newly generated bulbar interneurons causes strong impairment in mate recognition, thus resulting in a high pregnancy failure rate to familiar mating male odors. Taken together, our results indicate that adult neurogenesis is essential for specific brain functions such as persistent odor learning and mate recognition. PMID:21994486

  18. Neuromodulation of Olfactory Sensitivity in the Peripheral Olfactory Organs of the American Cockroach, Periplaneta americana

    PubMed Central

    Jung, Je Won; Kim, Jin-Hee; Pfeiffer, Rita; Ahn, Young-Joon; Page, Terry L.; Kwon, Hyung Wook

    2013-01-01

    Olfactory sensitivity exhibits daily fluctuations. Several studies have suggested that the olfactory system in insects is modulated by both biogenic amines and neuropeptides. However, molecular and neural mechanisms underlying olfactory modulation in the periphery remain unclear since neuronal circuits regulating olfactory sensitivity have not been identified. Here, we investigated the structure and function of these signaling pathways in the peripheral olfactory system of the American cockroach, Periplaneta americana, utilizing in situ hybridization, qRT-PCR, and electrophysiological approaches. We showed that tachykinin was co-localized with the octopamine receptor in antennal neurons located near the antennal nerves. In addition, the tachykinin receptor was found to be expressed in most of the olfactory receptor neurons in antennae. Functionally, the effects of direct injection of tachykinin peptides, dsRNAs of tachykinin, tachykinin receptors, and octopamine receptors provided further support for the view that both octopamine and tachykinin modulate olfactory sensitivity. Taken together, these findings demonstrated that octopamine and tachykinin in antennal neurons are olfactory regulators in the periphery. We propose here the hypothesis that octopamine released from neurons in the brain regulates the release of tachykinin from the octopamine receptor neurons in antennae, which in turn modulates the olfactory sensitivity of olfactory receptor neurons, which house tachykinin receptors. PMID:24244739

  19. Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb.

    PubMed

    Wanner, Adrian A; Genoud, Christel; Masudi, Tafheem; Siksou, Léa; Friedrich, Rainer W

    2016-06-01

    The dense reconstruction of neuronal circuits from volumetric electron microscopy (EM) data has the potential to uncover fundamental structure-function relationships in the brain. To address bottlenecks in the workflow of this emerging methodology, we developed a procedure for conductive sample embedding and a pipeline for neuron reconstruction. We reconstructed ∼98% of all neurons (>1,000) in the olfactory bulb of a zebrafish larva with high accuracy and annotated all synapses on subsets of neurons representing different types. The organization of the larval olfactory bulb showed marked differences from that of the adult but similarities to that of the insect antennal lobe. Interneurons comprised multiple types but granule cells were rare. Interglomerular projections of interneurons were complex and bidirectional. Projections were not random but biased toward glomerular groups receiving input from common types of sensory neurons. Hence, the interneuron network in the olfactory bulb exhibits a specific topological organization that is governed by glomerular identity. PMID:27089019

  20. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    NASA Astrophysics Data System (ADS)

    Zhou, Jun; Yang, Wei; Chen, Peihua; Liu, Qingjun; Wang, Ping

    2009-05-01

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  1. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    SciTech Connect

    Zhou Jun; Chen Peihua; Liu Qingjun; Wang Ping; Yang Wei

    2009-05-23

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  2. Immunohistochemical analysis for G protein in the olfactory organs of soft-shelled turtle, Pelodiscus sinensis.

    PubMed

    Nakamuta, Shoko; Yokosuka, Makoto; Taniguchi, Kazumi; Yamamoto, Yoshio; Nakamuta, Nobuaki

    2016-02-01

    In turtles, the epithelia lining the upper and lower chambers of the nasal cavity project axons to the ventral and dorsal parts of the olfactory bulbs, respectively. In a semi-aquatic soft-shelled turtle, Pelodiscus sinensis, more than 1,000 odorant receptor genes have been found, but it is not known where they are expressed. In this study, we aimed to clarify the distribution of cells expressing these genes in the olfactory organs of soft-shelled turtles. Immunoreactions for the Gαolf, the α subunit of G protein coupled to the odorant receptors, were detected on the surface of epithelia lining both the upper and lower chambers of the nasal cavity. The receptor cells in the epithelium of both chambers possessed cilia on the tip of their dendrites, whereas microvillous, non-ciliated, receptor cells were not found. These data suggest that the odorant receptor genes are expressed by the ciliated receptor cells in the upper and lower chamber epithelia. Precise location of the vomeronasal epithelium is not known at present. PMID:26440778

  3. Immunohistochemical analysis for G protein in the olfactory organs of soft-shelled turtle, Pelodiscus sinensis

    PubMed Central

    NAKAMUTA, Shoko; YOKOSUKA, Makoto; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; NAKAMUTA, Nobuaki

    2015-01-01

    In turtles, the epithelia lining the upper and lower chambers of the nasal cavity project axons to the ventral and dorsal parts of the olfactory bulbs, respectively. In a semi-aquatic soft-shelled turtle, Pelodiscus sinensis, more than 1,000 odorant receptor genes have been found, but it is not known where they are expressed. In this study, we aimed to clarify the distribution of cells expressing these genes in the olfactory organs of soft-shelled turtles. Immunoreactions for the Gαolf, the α subunit of G protein coupled to the odorant receptors, were detected on the surface of epithelia lining both the upper and lower chambers of the nasal cavity. The receptor cells in the epithelium of both chambers possessed cilia on the tip of their dendrites, whereas microvillous, non-ciliated, receptor cells were not found. These data suggest that the odorant receptor genes are expressed by the ciliated receptor cells in the upper and lower chamber epithelia. Precise location of the vomeronasal epithelium is not known at present. PMID:26440778

  4. The human olfactory receptor repertoire

    PubMed Central

    Zozulya, Sergey; Echeverri, Fernando; Nguyen, Trieu

    2001-01-01

    Background The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans. Results The strategy of our sequence database mining for full-length, functional candidate odorant receptor genes was based on the high overall sequence similarity and presence of a number of conserved sequence motifs in all known mammalian odorant receptors as well as the absence of introns in their coding sequences. We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors. A new nomenclature for human odorant receptors based on their chromosomal localization and phylogenetic analysis is proposed. We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors. Conclusions The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction. PMID:11423007

  5. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity.

    PubMed

    Lorenzon, Paolo; Redolfi, Nelly; Podolsky, Michael J; Zamparo, Ilaria; Franchi, Sira Angela; Pietra, Gianluca; Boccaccio, Anna; Menini, Anna; Murthy, Venkatesh N; Lodovichi, Claudia

    2015-01-01

    The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. PMID:25568110

  6. Continuous Neural Plasticity in the Olfactory Intrabulbar Circuitry

    PubMed Central

    Cummings, Diana M.; Belluscio, Leonardo

    2012-01-01

    In the mammalian brain each olfactory bulb contains two mirror-symmetric glomerular maps linked through a set of reciprocal intrabulbar projections. These projections connect isofunctional odor columns through synapses in the internal plexiform layer (IPL) to produce an intrabulbar map. Developmental studies show that initially intrabulbar projections broadly target the IPL on the opposite side of the bulb and refine postnatally to their adult precision by 7 weeks of age in an activity-dependent manner (Marks et al., 2006). In this study, we sought to determine the capacity of intrabulbar map to recover its precision after disruption. Using reversible naris closure in both juvenile and adult mice, we distorted the intrabulbar map and then removed the blocks for varying survival periods. Our results reveal that returning normal olfactory experience can indeed drive the re-refinement of intrabulbar projections but requires 9 weeks. Since activity also affects olfactory sensory neurons (OSNs) (Suh et al., 2006), we further examined the consequence of activity deprivation on P2-expressing OSNs and their associated glomeruli. Our findings indicate that while naris closure caused a marked decrease in P2-OSN number and P2-glomerular volume, axonal convergence was not lost and both were quickly restored within 3 weeks. By contrast, synaptic contacts within the IPL also decreased with sensory deprivation but required at least 6 weeks to recover. Thus, we conclude that recovery of the glomerular map precedes and likely drives the refinement of the intrabulbar map while IPL contacts recover gradually, possibly setting the pace for intrabulbar circuit restoration. PMID:20610751