Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Encoding social signals in the mouse main olfactory bulb


Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Urine-responsive mitral cells in the mouse main olfactory bulb.
Figure 2: Urine-responsive cells are activated by single components.
Figure 3: Activation of urine-responsive neurons by single components.
Figure 4: Sex- and strain-specific responses to urine volatiles.
Figure 5: Male-specific neurons respond to a novel semiochemical.
Figure 6: Synthetic MTMT enhances the attractiveness of urine to female mice.


  1. Baldwin, B. A. & Shillito, E. E. The effects of ablation of the olfactory bulbs on parturition and maternal behaviour in Soay sheep. Anim. Behav. 22, 220–223 (1974)

    Article  CAS  Google Scholar 

  2. Schaal, B. et al. Chemical and behavioural characterization of the rabbit mammary pheromone. Nature 424, 68–72 (2003)

    Article  ADS  CAS  Google Scholar 

  3. Yamaguchi, M. et al. Distinctive urinary odors governed by the major histocompatibility locus of the mouse. Proc. Natl Acad. Sci. USA 78, 5817–5820 (1981)

    Article  ADS  CAS  Google Scholar 

  4. Brennan, P. A. & Keverne, E. B. Something in the air? New insights into mammalian pheromones. Curr. Biol. 14, R81–R89 (2004)

    Article  CAS  Google Scholar 

  5. Dulac, C. & Torello, A. T. Molecular detection of pheromone signals in mammals: from genes to behaviour. Nature Rev. Neurosci. 4, 551–562 (2003)

    Article  CAS  Google Scholar 

  6. Andreolini, F., Jemiolo, B. & Novotny, M. V. Dynamics of excretion of urinary chemosignals in the house mouse (Mus musulus) during the natural estrous cycle. Experientia 43, 998–1002 (1987)

    Article  CAS  Google Scholar 

  7. Schwende, F. J., Wiesler, D., Jorgenson, J. W., Carmack, M. & Novotny, M. Urinary volatile constituents of the house mouse, Mus musculus, and their endocrine dependency. J Chem. Ecol. 12, 277–295 (1986)

    Article  CAS  Google Scholar 

  8. Harvey, S., Jemiolo, B. & Novotny, M. Pattern of volatile compounds in dominant and subordinate male mouse urine. J. Chem. Ecol. 14, 2061–2072 (1989)

    Article  Google Scholar 

  9. Jemiolo, B., Xie, T. M., Andreolini, F., Baker, A. E. M. & Novotny, M. The t complex of the mouse: chemical characterization by urinary volatile profiles. J. Chem. Ecol. 17, 353–367 (1990)

    Article  Google Scholar 

  10. Schaefer, M. L., Young, D. A. & Restrepo, D. Olfactory fingerprints for major histocompatibility complex-determined body odors. J. Neurosci. 21, 2481–2487 (2001)

    Article  CAS  Google Scholar 

  11. Schaefer, M. L., Yamazaki, K., Osada, K., Restrepo, D. & Beauchamp, G. K. Olfactory fingerprints for major histocompatibility complex-determined body odors II: relationship among odor maps, genetics, odor composition, and behavior. J. Neurosci. 22, 9513–9521 (2002)

    Article  CAS  Google Scholar 

  12. Lodovichi, C., Belluscio, L. & Katz, L. C. Functional topography of connections linking mirror-symmetric maps in the mouse olfactory bulb. Neuron 38, 265–276 (2003)

    Article  CAS  Google Scholar 

  13. Belluscio, L., Lodovichi, C., Feinstein, P., Mombaerts, P. & Katz, L. C. Odorant receptors instruct functional circuitry in the mouse olfactory bulb. Nature 419, 296–300 (2002)

    Article  ADS  CAS  Google Scholar 

  14. Wadhams, L. Coupled gas chromatography-single cell recording: a new technique for use in the analysis of insect pheromones. Z. Naturforsch. 37c, 947–952 (1982)

    Article  CAS  Google Scholar 

  15. Stensmyr, M. C., Giordano, E., Balloi, A., Angioy, A. M. & Hansson, B. S. Novel natural ligands for Drosophila olfactory receptor neurones. J. Exp. Biol. 206, 715–724 (2003)

    Article  CAS  Google Scholar 

  16. Kayali-Sayadi, M. N., Bautista, J. M., Polo-Diez, L. M. & Salazar, I. Identification of pheromones in mouse urine by head-space solid phase microextraction followed by gas chromatography-mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 796, 55–62 (2003)

    Article  CAS  Google Scholar 

  17. Louch, D., Motlagh, S. & Pawliszyn, J. Dynamics of organic compound extraction from water using liquid-coated fused silica fibers. Anal. Chem. 64, 1187–1199 (1992)

    Article  CAS  Google Scholar 

  18. Baek, H. H. & Kim, H. J. Solid phase microextraction-gas chromatography-olfactometry of soy sauce based on sample dilution analysis. Food Sci. Biotech. 13, 90–95 (2004)

    CAS  Google Scholar 

  19. Lee, S. N., Kim, N. S. & Lee, D. S. Comparative study of extraction techniques for determination of garlic flavor components by gas chromatography-mass spectrometry. Anal. Bioanal. Chem. 337, 749–756 (2003)

    Article  Google Scholar 

  20. Torrens, J., Rui-Aumatell, M., Lopez-Tamames, E. & Buxaderas, S. Volatile compounds of red and white wines by headspace ETH solid-phase microextraction using different fibers. J. Chromatogr. Sci. 42, 310–316 (2004)

    Article  CAS  Google Scholar 

  21. 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)

    Article  CAS  Google Scholar 

  22. Schutte, L. One-step synthesis of dithiohemiacetals, a new class of compounds. Tetrahedr. Lett. 12, 2321–2322 (1971)

    Article  Google Scholar 

  23. Singer, A. G. et al. Dimethyl disulfide: an attractant pheromone in hamster vaginal secretion. Science 191, 948–950 (1976)

    Article  ADS  CAS  Google Scholar 

  24. Galef, B. G. Jr, Mason, J. R., Preti, G. & Bean, N. J. Carbon disulfide: a semiochemical mediating socially-induced diet choice in rats. Physiol. Behav. 42, 119–124 (1988)

    Article  CAS  Google Scholar 

  25. Scott, J. W. & Pfaff, D. W. Behavioral and electrophysiological responses of female mice to male urine odors. Physiol. Behav. 5, 407–411 (1970)

    Article  CAS  Google Scholar 

  26. Doty, R. L., Green, P. A., Ram, C. & Yankell, S. L. Communication of gender from human breath odors: relationship to perceived intensity and pleasantness. Horm. Behav. 16, 13–22 (1982)

    Article  CAS  Google Scholar 

  27. Wallace, P. Individual discrimination of humans by odor. Physiol. Behav. 19, 577–579 (1977)

    Article  CAS  Google Scholar 

  28. 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)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  30. Novotny, M., Harvey, S. & Jemiolo, B. Chemistry of male dominance in the house mouse, Mus domesticus . Experientia 46, 109–113 (1990)

    Article  CAS  Google Scholar 

  31. Shinoda, K., Shiotani, Y. & Osawa, Y. “Necklace olfactory glomeruli” form unique components of the rat primary olfactory system. J. Comp. Neurol. 284, 362–373 (1989)

    Article  CAS  Google Scholar 

  32. Weruaga, E. et al. A sexually dimorphic group of atypical glomeruli in the mouse olfactory bulb. Chem. Senses 26, 7–15 (2001)

    Article  CAS  Google Scholar 

  33. Lin, W., Arellano, J., Slotnick, B. & Restrepo, D. Odors detected by mice deficient in cyclic nucleotide-gated channel subunit A2 stimulate the main olfactory system. J. Neurosci. 24, 3703–3710 (2004)

    Article  CAS  Google Scholar 

  34. Hildebrand, J. G. & Shepherd, G. M. Mechanisms of olfactory discrimination: converging evidence for common principles across phyla. Annu. Rev. Neurosci. 20, 595–631 (1997)

    Article  CAS  Google Scholar 

  35. Mori, K. Relation of chemical structure to specificity of response in olfactory glomeruli. Curr. Opin. Neurobiol. 5, 467–474 (1995)

    Article  CAS  Google Scholar 

  36. Friedrich, R. W. & Laurent, G. Dynamic optimization of odor representations by slow temporal patterning of mitral cell activity. Science 291, 889–894 (2001)

    Article  ADS  CAS  Google Scholar 

  37. Motokizawa, F. Odor representation and discrimination in mitral/tufted cells of the rat olfactory bulb. Exp. Brain Res. 112, 24–34 (1996)

    Article  CAS  Google Scholar 

  38. Tanabe, T., Iino, M. & Takagi, S. F. Discrimination of odors in olfactory bulb, pyriform-amygdaloid areas, and orbitofrontal cortex of the monkey. J. Neurophysiol. 38, 1284–1296 (1975)

    Article  CAS  Google Scholar 

  39. Friedrich, R. W., Habermann, C. J. & Laurent, G. Multiplexing using synchrony in the zebrafish olfactory bulb. Nature Neurosci. 7, 862–871 (2004)

    Article  CAS  Google Scholar 

  40. Wang, J. W., Wong, A. M., Flores, J., Vosshall, L. B. & Axel, R. Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell 112, 271–282 (2003)

    Article  CAS  Google Scholar 

  41. Wilson, R. I., Turner, G. C. & Laurent, G. Transformation of olfactory representations in the Drosophila antennal lobe. Science 303, 366–370 (2004)

    Article  ADS  CAS  Google Scholar 

  42. Vosshall, L. B., Amrein, H., Morozov, P. S., Rzhetsky, A. & Axel, R. A spatial map of olfactory receptor expression in the Drosophila antenna. Cell 96, 725–736 (1999)

    Article  CAS  Google Scholar 

  43. Clyne, P. J. et al. A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila . Neuron 22, 327–338 (1999)

    Article  CAS  Google Scholar 

  44. Ngai, J., Dowling, M. M., Buck, L., Axel, R. & Chess, A. The family of genes encoding odorant receptors in the channel catfish. Cell 72, 657–666 (1993)

    Article  CAS  Google Scholar 

  45. Miyashita, K. & Robinson, A. B. Identification of compounds in mouse urine vapor by gas chromatography and mass spectrometry. Mech. Ageing Dev. 13, 177–184 (1980)

    Article  CAS  Google Scholar 

  46. Bocchini, P., Andalo, C., Bonfiglioli, D. & Galletti, G. C. Solid-phase microextraction gas chromatography/mass spectrometric analysis of volatile organic compounds in water. Rapid Commun. Mass Spectrom. 13, 2133–2139 (1999)

    Article  ADS  CAS  Google Scholar 

  47. Contarini, G. & Povolo, M. Volatile fraction of milk: comparison between purge and trap and solid phase microextraction techniques. J. Agric. Food Chem. 50, 7350–7355 (2002)

    Article  CAS  Google Scholar 

  48. Fu, S. G., Yoon, Y. & Bazemore, R. Aroma-active components in fermented bamboo shoots. J. Agric. Food Chem. 50, 549–554 (2002)

    Article  CAS  Google Scholar 

  49. Brody, C. D. & Hopfield, J. J. Simple networks for spike-timing-based computation, with application to olfactory processing. Neuron 37, 843–852 (2003)

    Article  CAS  Google Scholar 

  50. Laurent, G. Olfactory network dynamics and the coding of multidimensional signals. Nature Rev. Neurosci. 3, 884–895 (2002)

    Article  CAS  Google Scholar 

Download references


We thank R. Axel, M. Ehlers, R. Mooney, D. Fitzpatrick and members of the Katz laboratory for critical comments on the manuscript; J. Jin, R. Irving, G. Dubay and L. Nielsen for technical assistance; and X. Han for critical assistance with chemical analysis. This work is supported by the NIH (NICDS) (L.C.K.), the Broad Foundation (D.Y.L.), NSF (E.B.), the Petroleum Research Fund, administered by the American Chemical Society (E.B.), and the Berryman Institute (E.B.). L.C.K. is an Investigator in the Howard Hughes Medical Institute.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Da Yu Lin.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Methods

This file contains details on constructing cell response map and synthesis of (methylthio)methanethiol. (DOC 28 kb)

Supplementary Figure S1

Clustered organization of urine responsive neurons in the main olfactory bulb. (PPT 263 kb)

Supplementary Figure S2

Optical imaging of intrinsic signals reveals no glomerular activation in response to urine odour on dorsal surface of the MOB. (PPT 4482 kb)

Supplementary Figure S3

Schematic representation of a gas chromatography-electrophysiology (GC-E) experiment. (PPT 80 kb)

Supplementary Figure S4

Urine responsive cells activated by multiple compounds in urine. (PPT 340 kb)

Supplementary Figure S5

Averaging multiple GC runs does not reveal the presence of additional weak responses. (PPT 608 kb)

Supplementary Figure S6

Separated compounds present in urine provide a rich source of odourant stimuli detectable by human observers. (PPT 94 kb)

Supplementary Figure S7

The pheromone 6-hydoxy-6-methyl-3-heptanone (6H6M3H) is not responsible for excitation of male-urine selective mitral cells. (PPT 195 kb)

Supplementary Figure S8

Scatter plots comparing the investigation times for intact, castrated and MTMT-containing urine. (PPT 58 kb)

Supplementary Figure S9

Neuronal responses elicited by MTMT are independent of other components in castrated mouse urine. (PPT 559 kb)

Supplementary Figure Legends

Legends to accompany the above Supplementary Figures S1-S9. (DOC 36 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lin, D., Zhang, SZ., Block, E. et al. Encoding social signals in the mouse main olfactory bulb. Nature 434, 470–477 (2005).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing