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.

  • Letter
  • Published:

Odorant receptors instruct functional circuitry in the mouse olfactory bulb


The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium1. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections2. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 → M71, in which a functionally characterized receptor, rI73,4, has been substituted into the M71 receptor locus5. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 → M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 → M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb.

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

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Odorant induced activation of rI7 → M71 glomeruli detected by intrinsic signal imaging.
Figure 2: rI7 → M71 glomeruli are innervated by postsynaptic neurons.
Figure 3: In vivo recording from a mitral cell responding to rI7 ligands.
Figure 4: Reciprocal connection between isofunctional glomeruli.

Similar content being viewed by others


  1. 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 

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

    Article  CAS  Google Scholar 

  3. Zhao, H. et al. Functional expression of a mammalian odorant receptor. Science 279, 237–242 (1998)

    Article  ADS  CAS  Google Scholar 

  4. Araneda, R. C., Kini, A. D. & Firestein, S. The molecular receptive range of an odorant receptor. Nature Neurosci. 3, 1248–1255 (2000)

    Article  CAS  Google Scholar 

  5. Bozza, T., Feinstein, P., Zheng, C. & Mombaerts, P. Odorant receptor expression defines functional units in the mouse olfactory system. J. Neurosci. 22, 3033–3043 (2002)

    Article  CAS  Google Scholar 

  6. 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 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Wang, F., Nemes, A., Mendelsohn, M. & Axel, R. Odorant receptors govern the formation of a precise topographic map. Cell 93, 47–60 (1998)

    Article  CAS  Google Scholar 

  10. Rubin, B. D. & Katz, L. C. Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron 23, 499–511 (1999)

    Article  CAS  Google Scholar 

  11. Johnson, B. A. & Leon, M. Modular representations of odorants in the glomerular layer of the rat olfactory bulb and the effects of stimulus concentration. J. Comp. Neurol. 422, 496–509 (2000)

    Article  CAS  Google Scholar 

  12. Uchida, N., Takahashi, Y. K., Tanifuji, M. & Mori, K. Odor maps in the mammalian olfactory bulb: domain organization and odorant structural features. Nature Neurosci. 3, 1035–1043 (2000)

    Article  CAS  Google Scholar 

  13. Belluscio, L. & Katz, L. C. Symmetry, stereotypy, and topography of odorant representations in mouse olfactory bulbs. J. Neurosci. 21, 2113–2122 (2001)

    Article  CAS  Google Scholar 

  14. Meister, M. & Bonhoeffer, T. Tuning and topography in an odor map on the rat olfactory bulb. J. Neurosci. 21, 1351–1360 (2001)

    Article  CAS  Google Scholar 

  15. Graziadei, P. P., Levine, R. R. & Graziadei, G. A. Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. Proc. Natl Acad. Sci. USA 75, 5230–5234 (1978)

    Article  ADS  CAS  Google Scholar 

  16. Bulfone, A. et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron 21, 1273–1282 (1998)

    Article  CAS  Google Scholar 

  17. Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000)

    Article  CAS  Google Scholar 

  18. LaMantia, A. S. & Purves, D. Development of glomerular pattern visualized in the olfactory bulbs of living mice. Nature 341, 646–649 (1989)

    Article  ADS  CAS  Google Scholar 

  19. Buck, L. B. Information coding in the vertebrate olfactory system. Annu. Rev. Neurosci. 19, 517–544 (1996)

    Article  CAS  Google Scholar 

  20. Luo, M. & Katz, L. C. Response correlation maps of neurons in the mammalian olfactory bulb. Neuron 32, 1165–1179 (2001)

    Article  CAS  Google Scholar 

  21. Shipley, M. T. & Ennis, M. Functional organization of olfactory system. J. Neurobiol. 30, 123–176 (1996)

    Article  CAS  Google Scholar 

  22. Zou, Z., Horowitz, L. F., Montmayeur, J. P., Snapper, S. & Buck, L. B. Genetic tracing reveals a stereotyped sensory map in the olfactory cortex. Nature 414, 173–179 (2001)

    Article  ADS  CAS  Google Scholar 

  23. Schoenfeld, T. A., Marchand, J. E. & Macrides, F. Topographic organization of tufted cell axonal projections in the hamster main olfactory bulb: an intrabulbar associational system. J. Comp. Neurol. 235, 503–518 (1985)

    Article  CAS  Google Scholar 

  24. Liu, W. L. & Shipley, M. T. Intrabulbar associational system in the rat olfactory bulb comprises cholecystokinin-containing tufted cells that synapse onto the dendrites of GABAergic granule cells. J. Comp. Neurol. 346, 541–558 (1994)

    Article  CAS  Google Scholar 

  25. Buonviso, N., Chaput, M. A. & Scott, J. W. Mitral cell-to-glomerulus connectivity: an HRP study of the orientation of mitral cell apical dendrites. J. Comp. Neurol. 307, 57–64 (1991)

    Article  CAS  Google Scholar 

  26. Strotmann, J., Conzelmann, S., Beck, A., Feinstein, P., Breer, H. & Peter Mombaerts Local permutations in the glomerular array of the mouse olfactory bulb. J. Neurosci. 20, 6927–6938 (2001)

    Article  Google Scholar 

  27. Schaefer, M. L., Finger, T. E. & Restrepo, D. Variability of position of the P2 glomerulus within a map of the mouse olfactory bulb. J. Comp. Neurol. 436, 351–362 (2001)

    Article  CAS  Google Scholar 

  28. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996)

    Article  ADS  CAS  Google Scholar 

  29. Jefferis, G. S., Marin, E. C., Stocker, R. F. & Luo, L. Target neuron prespecification in the olfactory map of Drosophila. Nature 414, 204–208 (2001)

    Article  ADS  CAS  Google Scholar 

Download references


We thank G. Feng for providing the YFP-G mice. L.C.K. is an Investigator in the Howard Hughes Medical Institute, L.B. is a Burroughs Wellcome Fellow in Neuroscience, and grant support to P.M. was from the NIH.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Leonardo Belluscio.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • 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