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Non-redundant coding of aversive odours in the main olfactory pathway

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Abstract

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs)1,2,3,4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor5,6,7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

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Figure 1: Deleting the olfactory TAARs abolishes high-sensitivity amine and predator odour responses in the dorsal olfactory bulb.
Figure 2: Deletion of all olfactory Taar genes abolishes aversion to low concentrations of structurally diverse amines and predator urine.
Figure 3: Deletion of a single Taar gene abolishes aversion to a specific amine and to natural predator odours.

References

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

    CAS  Article  Google Scholar 

  2. Liberles, S. D. Trace amine-associated receptors are olfactory receptors in vertebrates. Ann. NY Acad. Sci. 1170, 168–172 (2009)

    ADS  CAS  Article  Google Scholar 

  3. Nei, M., Niimura, Y. & Nozawa, M. The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity. Nature Rev. Genet. 9, 951–963 (2008)

    CAS  Article  Google Scholar 

  4. Touhara, K. & Vosshall, L. B. Sensing odorants and pheromones with chemosensory receptors. Annu. Rev. Physiol. 71, 307–332 (2009)

    CAS  Article  Google Scholar 

  5. Wilson, R. I. & Mainen, Z. F. Early events in olfactory processing. Annu. Rev. Neurosci. 29, 163–201 (2006)

    CAS  Article  Google Scholar 

  6. Kauer, J. S. & White, J. Imaging and coding in the olfactory system. Annu. Rev. Neurosci. 24, 963–979 (2001)

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  8. Liberles, S. D. & Buck, L. B. A second class of chemosensory receptors in the olfactory epithelium. Nature 442, 645–650 (2006)

    ADS  CAS  Article  Google Scholar 

  9. Lindemann, L. et al. Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics 85, 372–385 (2005)

    CAS  Article  Google Scholar 

  10. Bozza, T., McGann, J. P., Mombaerts, P. & Wachowiak, M. In vivo imaging of neuronal activity by targeted expression of a genetically encoded probe in the mouse. Neuron 42, 9–21 (2004)

    CAS  Article  Google Scholar 

  11. Pacifico, R., Dewan, A., Cawley, D., Guo, C. & Bozza, T. An olfactory subsystem that mediates high-sensitivity detection of volatile amines. Cell Reports 2, 76–88 (2012)

    CAS  Article  Google Scholar 

  12. Johnson, M. A. et al. Neurons expressing trace amine-associated receptors project to discrete glomeruli and constitute an olfactory subsystem. Proc. Natl Acad. Sci. USA 109, 13410–13415 (2012)

    ADS  CAS  Article  Google Scholar 

  13. Zhang, J., Pacifico, R., Cawley, D., Feinstein, P. & Bozza, T. Ultrasensitive detection of amines by a trace amine associated receptor. J. Neurosci. 33, 3228–3239 (2013)

    CAS  Article  Google Scholar 

  14. Ferrero, D. M. et al. Detection and avoidance of a carnivore odor by prey. Proc. Natl Acad. Sci. USA 108, 11235–11240 (2011)

    ADS  CAS  Article  Google Scholar 

  15. Kobayakawa, K. et al. Innate versus learned odour processing in the mouse olfactory bulb. Nature 450, 503–508 (2007)

    ADS  CAS  Article  Google Scholar 

  16. Vernet-Maury, E., Polak, E. H. & Demael, A. Structure-activity relationship of stress-inducing odorants in the rat. J. Chem. Ecol. 10, 1007–1018 (1984)

    CAS  Article  Google Scholar 

  17. Fendt, M., Endres, T., Lowry, C. A., Apfelbach, R. & McGregor, I. S. TMT-induced autonomic and behavioral changes and the neural basis of its processing. Neurosci. Biobehav. Rev. 29, 1145–1156 (2005)

    CAS  Article  Google Scholar 

  18. Papes, F., Logan, D. W. & Stowers, L. The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141, 692–703 (2010)

    CAS  Article  Google Scholar 

  19. Ben-Shaul, Y., Katz, L. C., Mooney, R. & Dulac, C. In vivo vomeronasal stimulation reveals sensory encoding of conspecific and allospecific cues by the mouse accessory olfactory bulb. Proc. Natl Acad. Sci. USA 107, 5172–5177 (2010)

    ADS  CAS  Article  Google Scholar 

  20. Li, Q. et al. Synchronous evolution of an odor biosynthesis pathway and behavioral response. Curr. Biol. 23, 11–20 (2013)

    Article  Google Scholar 

  21. Kauer, J. S. Contributions of topography and parallel processing to odor coding in the vertebrate olfactory pathway. Trends Neurosci. 14, 79–85 (1991)

    CAS  Article  Google Scholar 

  22. Del Punta, K. et al. Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes. Nature 419, 70–74 (2002)

    ADS  CAS  Article  Google Scholar 

  23. Munger, S. D. et al. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning. Curr. Biol. 20, 1438–1444 (2010)

    CAS  Article  Google Scholar 

  24. Munger, S. D., Leinders-Zufall, T. & Zufall, F. Subsystem organization of the mammalian sense of smell. Annu. Rev. Physiol. 71, 115–140 (2009)

    CAS  Article  Google Scholar 

  25. Wu, S., Ying, G., Wu, Q. & Capecchi, M. R. Toward simpler and faster genome-wide mutagenesis in mice. Nature Genet. 39, 922–930 (2007)

    CAS  Article  Google Scholar 

  26. McGann, J. P. et al. Odorant representations are modulated by intra- but not interglomerular presynaptic inhibition of olfactory sensory neurons. Neuron 48, 1039–1053 (2005)

    CAS  Article  Google Scholar 

  27. Tang, S. H., Silva, F. J., Tsark, W. M. & Mann, J. R. A cre/loxP-deleter transgenic line in mouse strain 129S1/SvImJ. Genesis 32, 199–202 (2002)

    CAS  Article  Google Scholar 

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Acknowledgements

We thank T. Schmidt, C. Waldron, L. Tunmer, V. Dewan and the staff of the Philadelphia Zoo for collecting predator urine and for providing images of the animals. We thank D. Ferster for help with video tracking, D. Cawley, A. Ge and T. Alconada for help analysing behavioural data, the Northwestern University Center for Comparative Medicine for behavioural space, and the Northwestern University Biostatistics Collaboration Center for advice on statistical analyses. T.B. was a participant in the Visiting Scientist Program at HHMI Janelia Farm Research Campus. This work was supported by grants from the NIH/NIDCD (R01DC009640 to T.B. and F32DC012004 to A.D.), The Whitehall Foundation and The Brain Research Foundation (T.B.).

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Contributions

A.D., D.R. and T.B. planned the experiments. A.D. and R.Z. performed the behavioural analyses. R.P. and T.B. generated the mouse strains and performed in vivo imaging experiments. A.D., R.P., D.R. and T.B. analysed the data. A.D., R.P. and T.B. wrote the manuscript.

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Correspondence to Thomas Bozza.

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The authors declare no competing financial interests.

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This file contains Supplementary Figure 1, which compares the locomotor activity and weight of wild-type and homozygous ΔT2-9 mice. (PDF 345 kb)

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Dewan, A., Pacifico, R., Zhan, R. et al. Non-redundant coding of aversive odours in the main olfactory pathway. Nature 497, 486–489 (2013). https://doi.org/10.1038/nature12114

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