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Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium

Nature Neuroscience volume 6, pages 519–525 (2003)Cite this article

Abstract

It is commonly assumed that odorants are detected by the main olfactory epithelium (MOE) and pheromones are sensed through the vomeronasal organ (VNO). The complete loss of MOE-mediated olfaction in type-3 adenylyl cyclase knockout mice (AC3−/−) allowed us to examine chemosensory functions of the VNO in the absence of signaling through the MOE. Here we report that AC3−/− mice are able to detect certain volatile odorants via the VNO. These same odorants elicited electro-olfactogram transients in the VNO and MOE of wild-type mice, but only VNO responses in AC3−/− mice. This indicates that some odorants are detected through an AC3-independent pathway in the VNO.

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Figure 1: Disorganization of axonal projections from olfactory sensory neurons into the glomerular layer of AC3−/− mice.
Figure 2: Detection of odorants by the olfactory habituation assay.
Figure 3: AC3−/− mice detect some odorants.
Figure 4: AC3−/− mice do not show odorant-induced EOG responses in the MOE.
Figure 5: Bulbectomized wild-type mice cannot sense odorants that are detected by AC3−/− mice.
Figure 6: The VNO is activated by certain odorants.
Figure 7: MOE-lesioned mice are able to detect the same odorants detected by AC3−/− mice, (a) The MOE of 8-week wild-type mice were treated with ZnSO4, and the mice were examined for their ability to detect specific odorants.

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References

  1. Amoore, J. Molecular Basis of Odor 28–87 (Charles C. Thomas, Springfield, Illinois, 1970).

    Google Scholar 

  2. Ressler, K.J., Sullivan, S.L. & Buck, L.B. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79, 1245–1255 (1994).

    Article  CAS  Google Scholar 

  3. Vassar, R. et al. Topographic organization of sensory projections to the olfactory bulb. Cell 79, 981–991 (1994).

    Article  CAS  Google Scholar 

  4. Firestein, S. How the olfactory system makes sense of scents. Nature 413, 211–218 (2001).

    Article  CAS  Google Scholar 

  5. Dulac, C. Sensory coding of pheromone signals in mammals. Curr. Opin. Neurobiol. 10, 511–518 (2000).

    Article  CAS  Google Scholar 

  6. Buck, L.B. The molecular architecture of odor and pheromone sensing in mammals. Cell 100, 611–618 (2000).

    Article  CAS  Google Scholar 

  7. Zufall, F. & Munger, S.D. From odor and pheromone transduction to the organization of the sense of smell. Trends Neurosci. 24, 191–193 (2001).

    Article  CAS  Google Scholar 

  8. Rodriguez, I., Feinstein, P. & Mombaerts, P. Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97, 199–208 (1999).

    Article  CAS  Google Scholar 

  9. Dudley, C.A., Chakravarty, S. & Barnea, A. Female odors lead to rapid activation of mitogen-activated protein kinase (MAPK) in neurons of the vomeronasal system. Brain Res. 915, 32–46 (2001).

    Article  CAS  Google Scholar 

  10. Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187 (1991).

    Article  CAS  Google Scholar 

  11. Vassar, R., Ngai, J. & Axel, R. Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74, 309–318 (1993).

    Article  CAS  Google Scholar 

  12. Jones, D.T. & Reed, R.R. Golf: an olfactory neuron specific G protein involved in odorant signal transduction. Science 244, 790–795 (1989).

    Article  CAS  Google Scholar 

  13. Belluscio, L., Gold, G.H., Nemes, A. & Axel, R. Mice deficient in G(olf) are anosmic. Neuron 20, 69–81 (1998).

    Article  CAS  Google Scholar 

  14. Wong, S.T. et al. Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27, 487–497 (2000).

    Article  CAS  Google Scholar 

  15. Bakalyar, H.A. & Reed, R.R. Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250, 1403–1406 (1990).

    Article  CAS  Google Scholar 

  16. Wei, J., Wayman, G. & Storm, D.R. Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. J. Biol. Chem. 271, 24231–24235 (1996).

    Article  CAS  Google Scholar 

  17. Wei, J. et al. Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in neurons: a mechanism for attenuation of olfactory signals. Neuron 21, 495–504 (1998).

    Article  CAS  Google Scholar 

  18. Brunet, L.J., Gold, G.H. & Ngai, J. General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17, 681–693 (1996).

    Article  CAS  Google Scholar 

  19. Lowe, G. & Gold, G.H. Contribution of the ciliary cyclic nucleotide-gated conductance to olfactory transduction in the salamander. J. Physiol. 462, 175–196 (1993).

    Article  CAS  Google Scholar 

  20. Dhallan, R.S., Yau, K.W., Schrader, K.A. & Reed, R.R. Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 347, 184–187 (1990).

    Article  CAS  Google Scholar 

  21. Berghard, A. & Buck, L.B. Sensory transduction in vomeronasal neurons: evidence for G alpha o, G alpha i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J. Neurosci. 16, 909–918 (1996).

    Article  CAS  Google Scholar 

  22. Berghard, A., Buck, L.B. & Liman, E.R. Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs. Proc. Natl. Acad. Sci. USA 93, 2365–2369 (1996).

    Article  CAS  Google Scholar 

  23. Mombaerts, P. et al. Visualizing an olfactory sensory map. Cell 87, 675–686 (1996).

    Article  CAS  Google Scholar 

  24. Puche, A.C. & Shipley, M.T. Odor-induced, activity-dependent transneuronal gene induction in vitro: mediation by NMDA receptors. J. Neurosci. 19, 1359–1370 (1999).

    Article  CAS  Google Scholar 

  25. Baker, H., Morel, K., Stone, D.M. & Maruniak, J.A. Adult naris closure profoundly reduces tyrosine hydroxylase expression in mouse olfactory bulb. Brain Res. 614, 109–116 (1993).

    Article  CAS  Google Scholar 

  26. Brown, R.E., Singh, P.B. & Roser, B. The major histocompatibility complex and the chemosensory recognition of individuality in rats. Physiol. Behav. 40, 65–73 (1987).

    Article  CAS  Google Scholar 

  27. Gregg, B. & Thiessen, D.D. A simple method of olfactory discrimination of urines for the Mongolian gerbil, Meriones unguiculatus. Physiol. Behav. 26, 1133–1136 (1981).

    Article  CAS  Google Scholar 

  28. Breer, H., Boekhoff, I. & Tareilus, E. Rapid kinetics of second messenger formation in olfactory transduction. Nature 345, 65–68 (1990).

    Article  CAS  Google Scholar 

  29. Sklar, P.B., Anholt, R.R. & Snyder, S.H. The odorant-sensitive adenylate cyclase of olfactory receptor cells. Differential stimulation by distinct classes of odorants. J. Biol. Chem. 261, 15538–15543 (1986).

    CAS  PubMed  Google Scholar 

  30. Yamada, K., Itoh, R. & Ohta, A. Influence of pyrazine derivatives on the day of vaginal opening in juvenile female rats. Jpn. J. Pharmacol. 49, 529–530 (1989).

    Article  CAS  Google Scholar 

  31. Sam, M. et al. Odorants may arouse instinctive behaviours. Nature 412, 142 (2001).

    Article  CAS  Google Scholar 

  32. Leinders-Zufall, T. et al. Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature 405, 792–796 (2000).

    Article  CAS  Google Scholar 

  33. Novotny, M., Jemiolo, B., Harvey, S., Wiesler, D. & Marchlewska-Koj, A. Adrenal-mediated endogenous metabolites inhibit puberty in female mice. Science 231, 722–725 (1986).

    Article  CAS  Google Scholar 

  34. Kolunie, J.M. & Stern, J.M. Maternal aggression in rats: effects of olfactory bulbectomy, ZnSO4-induced anosmia and vomeronasal organ removal. Horm. Behav. 29, 492–518 (1995).

    Article  CAS  Google Scholar 

  35. Harding, J.W., Getchell, T.V. & Margolis, F.L. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology. Brain Res. 140, 271–285 (1978).

    Article  CAS  Google Scholar 

  36. Leypold, B.G. et al. Altered sexual and social behaviors in trp2 mutant mice. Proc. Natl. Acad. Sci. USA 99, 6376–6381 (2002).

    Article  CAS  Google Scholar 

  37. Stowers, L., Holy, T.E., Meister, M., Dulac, C. & Koentges, G. Loss of sex discrimination and male–male aggression in mice deficient for TRP2. Science 295, 1493–1500 (2002).

    Article  CAS  Google Scholar 

  38. Gore, A.C., Wersinger, S.R. & Rissman, E.F. Effects of female pheromones on gonadotropin-releasing hormone gene expression and luteinizing hormone release in male wild-type and oestrogen receptor-alpha knockout mice. J. Neuroendocrinol. 12, 1200–1204 (2000).

    Article  CAS  Google Scholar 

  39. Briand, L. et al. Odorant and pheromone binding by aphrodisin, a hamster aphrodisiac protein. FEBS Lett. 476, 179–185 (2000).

    Article  CAS  Google Scholar 

  40. Hagino-Yamagishi, K. et al. The mouse putative pheromone receptor was specifically activated by stimulation with male mouse urine. J. Biochem. (Tokyo) 129, 509–512 (2001).

    Article  CAS  Google Scholar 

  41. Dulac, C. & Axel, R. A novel family of genes encoding putative pheromone receptors in mammals. Cell 83, 195–206 (1995).

    Article  CAS  Google Scholar 

  42. Dulac, C. & Axel, R. Expression of candidate pheromone receptor genes in vomeronasal neurons. Chem. Senses 23, 467–475 (1998).

    Article  CAS  Google Scholar 

  43. Liman, E.R., Corey, D.P. & Dulac, C. TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc. Natl. Acad. Sci. USA 96, 5791–5796 (1999).

    Article  CAS  Google Scholar 

  44. Fewell, G.D. & Meredith, M. Experience facilitates vomeronasal and olfactory influence on Fos expression in medial preoptic area during pheromone exposure or mating in male hamsters. Brain Res. 941, 91–106 (2002).

    Article  CAS  Google Scholar 

  45. Petrulis, A., Peng, M. & Johnston, R.E. Effects of vomeronasal organ removal on individual odor discrimination, sex-odor preference, and scent marking by female hamsters. Physiol. Behav. 66, 73–83 (1999).

    Article  CAS  Google Scholar 

  46. Sipos, M.L., Wysocki, C.J., Nyby, J.G., Wysocki, L. & Nemura, T.A. An ephemeral pheromone of female house mice: perception via the main and accessory olfactory systems. Physiol. Behav. 58, 529–534 (1995).

    Article  CAS  Google Scholar 

  47. Halpern, M. and Kubie, J.L. The role of the ophidian vomeronasal system in species-typical behavior. Trends Neurosci. 472–477 (1984).

  48. Horowitz, L.F., Montmayeur, J.P., Echelard, Y. & Buck, L.B. A genetic approach to trace neural circuits. Proc. Natl. Acad. Sci. USA 96, 3194–3199 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank D. Restrepo for scientific discussions, and J. Athos, V.V. Pineda, W.C. Watt and members of the Storm lab for critical reading of the manuscript. This study was supported by National Institutes of Health (DC04156). K. Trinh was supported in part by PHS NRSA T32 GMO7270 and HL07312-22.

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  1. Molecular and Cellular Biology Program and Department of Pharmacology, University of Washington, Box 357750, 1959 NE Pacific St., Seattle, 98195, Washington, USA

    Kien Trinh & Daniel R. Storm

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Correspondence to Daniel R. Storm.

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D.R.S.is a member of the Scientific Advisory Board for Helicon Corp.

Supplementary information

Supplementary Fig. 1.

Representative images of tyrosine hydroxylase (TH) cells in the glomerular layer of the olfactory bulb. (a, b) Confocal images of TH expressing cells in the glomerular layer of wild type (a) and AC3-/- mice (b) olfactory bulbs. There was a significant decrease in the number of TH positive cells in AC3-/- mice. (c, d) Magnified images of the glomerular layer of OMP-ires-tua-lacZ wild type and AC3-/- mice. Cells within the olfactory bulb were imaged with the nuclear stain (red), neutral red, and olfactory axonal terminal with β-galactosidase staining (blue). The reduction in TH positive cells was not due to the decrease in periglomerular cells (PGL). (PDF 137 kb)

Supplementary Fig. 2.

Representative electro-vomeronasal-olfactograms for citralva, lilial and isomethone in the VNO of AC3-/- mice. These three odorants did not elicit behavioral responses in AC3-/- mice. These compounds also did not elicit a potential change in the VNO compared to 2-heptanone, which induced a negative potential change. Odorant concentrations were 50 μM lilial, 50 μM isomethone, 50 μM 2-heptanone and 5 µM citralva. EVG was measured as described in Methods. (PDF 39 kb)

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Trinh, K., Storm, D. Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nat Neurosci 6, 519–525 (2003). https://doi.org/10.1038/nn1039

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