Abstract
The vomeronasal organ (VNO) is a chemoreceptive organ that is thought to transduce pheromones into electrical responses that regulate sexual, hormonal and reproductive function in mammals1,2,3,4,5. The characteristics of pheromone signal detection by vomeronasal neurons remain unclear3,5. Here we use a mouse VNO slice preparation to show that six putative pheromones evoke excitatory responses in single vomeronasal neurons, leading to action potential generation and elevated calcium entry. The detection threshold for some of these chemicals is remarkably low, near 10-11 M, placing these neurons among the most sensitive chemodetectors in mammals. Using confocal calcium imaging, we map the epithelial representation of the pheromones to show that each of the ligands activates a unique, nonoverlapping subset of vomeronasal neurons located in apical zones of the epithelium. These neurons show highly selective tuning properties and their tuning curves do not broaden with increasing concentrations of ligand, unlike those of receptor neurons in the main olfactory epithelium. These findings provide a basis for understanding chemical signals that regulate mammalian communication and sexual behaviour.
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References
Halpern, M. The organization and function of the vomeronasal system. Annu. Rev. Neurosci. 10, 325–362 (1987).
Wysocki, C. J. & Meredith, M. in Neurobiology of Taste and Smell (eds Finger, T. E. & Silver, W. L.) 125– 150 (Wiley & Sons, New York, 1987).
Keverne, E. B. The vomeronasal organ. Science 286, 716– 723 (1999).
Bargmann, C. I. Olfactory receptors, vomeronasal receptors, and the organization of olfactory information. Cell 90, 585– 587 (1997).
Tirindelli, R., Mucignat-Caretta, C. & Ryba, N. J. P. Molecular aspects of pheromonal communication via the vomeronasal organ of mammals. Trends Neurosci. 21, 482–486 (1998).
Novotny, M. V., Jemiolo, B., Harvey, S., Wiesler, D. & Marchlewska-Koj, A. Adrenal-mediated endogenous metabolites inhibit puberty in female mice. Science 231, 722– 725 (1986).
Jemiolo, B., Harvey, S. & Novotny, M. V. Promotion of the Whitten effect in female mice by synthetic analogs of male urinary constituents. Proc. Natl Acad. Sci. USA 83, 4576–4579 ( 1986).
Novotny, M. V., Ma, W., Wiesler, D. & Zidek, L. Positive identification of the puberty-accelerating pheromone of the house mouse: the volatiles associating with the major urinary protein. Proc. R. Soc. Lond. B 266, 2017–2022 (1999).
Jemiolo, B., Andreolini, F., Xie, T.-M., Wiesler, D. & Novotny, M. V. Puberty-affecting synthetic analogs of urinary chemosignals in the house mouse, Mus domesticus. Physiol. Behav. 46, 293–298 (1989).
Novotny, M. V. et al. A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice. Chem. Biol. 6, 377–383 ( 1999).
Inamura, K., Kashiwayanagi, M. & Kurihara, K. Inositol-1,4,5-triphosphate induces responses in receptor neurons in rat vomeronasal sensory slices. Chem. Senses 22, 93–103 (1997).
Restrepo, D., Okada, Y. & Teeter, J. H. Odorant-regulated Ca2+ gradients in rat olfactory neurons. J. Gen. Physiol. 102, 907–924 (1993).
Bozza, T. C. & Kauer, J. S. Odorant response properties of convergent olfactory receptor neurons. J. Neurosci. 18, 4560–4569 (1998).
Leinders-Zufall, T., Greer, C. A., Shepherd, G. M. & Zufall, F. Imaging odor-induced calcium transients in single olfactory cilia: specificity of activation and role in transduction. J. Neurosci. 18, 5630–5639 (1998).
Dulac, C. & Axel, R. A novel family of genes encoding putative pheromone receptors in mammals. Cell 83, 195–206 (1995).
Herrada, G. & Dulac, C. A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90, 763– 773 (1997).
Matsunami, I. & Buck, L. B. A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90, 775–784 (1997).
Ryba, N. J. P. & Tirindelli, R. A new multigene family of putative pheromone receptors. Neuron 19, 371–379 (1997).
Jia, C. & Halpern, M. Subclasses of vomeronasal receptor neurons: differential expression of G protein (Giα2 and Goα) and segregated projections to the accessory olfactory bulb. Brain Res. 719, 117–128 ( 1996).
Berghard, A. & Buck, L. Sensory transduction in vomeronasal neurons: evidence for G α 0, G α i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J. Neurosci. 16, 909– 918 (1996).
Kauer, J. S. Contributions of topography and parallel processing to odor coding in the vertebrate olfactory pathway. Trends Neurosci. 14, 79–85 (1991).
Mori, K. & Yoshihara, Y. Molecular recognition and olfactory processing in the mammalian olfactory system. Prog. Neurobiol. 45, 585–620 ( 1995).
Duchamp-Viret, P., Chaput, M. A. & Duchamp, A. Odor response properties of rat olfactory receptor neurons. Science 284, 2171–2174 (1999).
Malnic, B., Hirono, J., Sato, T. & Buck, L. B. Combinatorial receptor codes for odors. Cell 96, 713– 723 (1999).
Hildebrand, J. G. & Shepherd, G. M. Mechanisms of olfactory discrimination: converging evidence for common principles across phyla. Annu. Rev. Neurosci. 20, 595– 631 (1997).
Zidek, L., Joo, A., Ma, W., Miao, Z. & Novotny, M. V. 4,5-dihydrothiazoles exhibit no correlations between their puberty-acceleration and activity for soluble binding proteins in the house mouse. Chem. Senses (submitted).
Rodriguez, I., Feinstein, P. & Mombaerts, P. Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97, 199–208 (1999).
Belluscio, L., Koentges, G., Axel, R. & Dulac, C. A map of pheromone receptor activation in the mammalian brain. Cell 97 , 209–220 (1999).
Leinders-Zufall, T., Rand, M. N., Shepherd, G. M., Greer, C. A. & Zufall, F. Calcium entry through cyclic nucleotide-gated channels in individual cilia of olfactory receptor cells: spatiotemporal dynamics. J. Neurosci. 17, 4136– 4148 (1997).
Novotny, M., Schwende, F. J., Wiesler, D., Jorgenson, J. W. & Carmack, M. Identification of a testosterone-dependent unique volatile constituent of male mouse urine: 7-exo-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]-3-octene. Experientia 40, 217–219 (1984).
Acknowledgements
This study was supported by grants from the NIH to T.L.-Z., M.V.N., M.T.S. and F.Z., and by an intramural grant from the University of Maryland (F.Z.). A.P.L. was a recipient of an NIDCD training grant. We thank R. Bock for programming spike analysis software.
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Leinders-Zufall, T., Lane, A., Puche, A. et al. Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature 405, 792–796 (2000). https://doi.org/10.1038/35015572
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DOI: https://doi.org/10.1038/35015572
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