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Perception of sniff phase in mouse olfaction


Olfactory systems encode odours by which neurons respond and by when they respond1,2,3. In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons4,5,6. Likewise, in a variety of neural systems, ranging from sensory periphery7,8 to cognitive centres9, neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system10,11. However, there is no evidence that mammalian olfactory systems read such cues12,13. To test whether mice perceive the timing of olfactory activation relative to the sniff cycle (‘sniff phase’), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses14,15. Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly11,16.

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Figure 1: Stimulating olfaction with light.
Figure 2: OMP–ChR2 mice perceive sniff phase.
Figure 3: Response of mitral/tufted cells to light stimulation.


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

    Article  CAS  Google Scholar 

  2. 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 

  3. Junek, S., Kludt, E., Wolf, F. & Schild, D. Olfactory coding with patterns of response latencies. Neuron 67, 872–884 (2011)

    Article  Google Scholar 

  4. Macrides, F. & Chorover, S. L. Olfactory bulb units: activity correlated with inhalation cycles and odor quality. Science 175, 84–87 (1972)

    Article  ADS  CAS  Google Scholar 

  5. Chaput, M. & Holley, A. Single unit responses of olfactory bulb neurones to odour presentation in awake rabbits. J. Physiol. (Paris) 76, 551–558 (1980)

    CAS  Google Scholar 

  6. Spors, H., Wachowiak, M., Cohen, L. B. & Friedrich, R. W. Temporal dynamics and latency patterns of receptor neuron input to the olfactory bulb. J. Neurosci. 26, 1247–1259 (2006)

    Article  CAS  Google Scholar 

  7. Szabo, T. & Hagiwara, S. A latency-change mechanism involved in sensory coding of electric fish (mormyrids). Physiol. Behav. 2, 331–335 (1967)

    Article  Google Scholar 

  8. Gollisch, T. & Meister, M. Rapid neural coding in the retina with relative spike latencies. Science 319, 1108–1111 (2008)

    Article  ADS  CAS  Google Scholar 

  9. O'Keefe, J. & Recce, M. L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993)

    Article  CAS  Google Scholar 

  10. Hopfield, J. J. Pattern recognition computation using action potential timing for stimulus representation. Nature 376, 33–36 (1995)

    Article  ADS  CAS  Google Scholar 

  11. Schaefer, A. T. & Margrie, T. W. Spatiotemporal representations in the olfactory system. Trends Neurosci. 30, 92–100 (2007)

    Article  CAS  Google Scholar 

  12. Monod, B., Mouly, A. M., Vigouroux, M. & Holley, A. An investigation of some temporal aspects of olfactory coding with the model of multi-site electrical stimulation of the olfactory bulb in the rat. Behav . Brain Res. 33, 51–63 (1989)

    CAS  Google Scholar 

  13. Leon, M. & Johnson, B. A. Is there a spacetime continuum in olfaction? Cell. Mol. Life Sci. 66, 2135–2150 (2009)

    Article  CAS  Google Scholar 

  14. Cury, K. M. & Uchida, N. Robust odor coding via inhalation-coupled transient activity in the mammalian olfactory bulb. Neuron 68, 570–585 (2010)

    Article  CAS  Google Scholar 

  15. Shusterman, R., Smear, M., Koulakov, A. & Rinberg, D. Precise olfactory responses tile the sniff cycle. Nature Neurosci. 14, 1039–1044 (2011)

    Article  CAS  Google Scholar 

  16. Margrie, T. W. & Schaefer, A. T. Theta oscillation coupled spike latencies yield computational vigour in a mammalian sensory system. J. Physiol. (Lond.) 546, 363–374 (2003)

    Article  CAS  Google Scholar 

  17. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005)

    Article  CAS  Google Scholar 

  18. Raman, B., Joseph, J., Tang, J. & Stopfer, M. Temporally diverse firing patterns in olfactory receptor neurons underlie spatiotemporal neural codes for odors. J. Neurosci. 30, 1994–2006 (2010)

    Article  CAS  Google Scholar 

  19. Nagel, K. I. & Wilson, R. I. Biophysical mechanisms underlying olfactory receptor neuron dynamics. Nature Neurosci. 14, 208–216 (2011)

    Article  CAS  Google Scholar 

  20. Cang, J. & Isaacson, J. S. In vivo whole-cell recording of odor-evoked synaptic transmission in the rat olfactory bulb. J. Neurosci. 23, 4108–4116 (2003)

    Article  CAS  Google Scholar 

  21. Perkel, D. H. & Bullock, T. H. Neural coding. Neurosci. Res. Prog. Bull. 6, 219–349 (1968)

    Google Scholar 

  22. 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 

  23. Hall, C., Bell, C. & Zelick, R. Behavioral evidence of a latency code for stimulus intensity in mormyrid electric fish. J. Comp. Physiol. A 177, 29–39 (1995)

    Article  Google Scholar 

  24. Di Lorenzo, P. M., Leshchinskiy, S., Moroney, D. N. & Ozdoba, J. M. Making time count: functional evidence for temporal coding of taste sensation. Behav. Neurosci. 123, 14–25 (2009)

    Article  CAS  Google Scholar 

  25. Jacobs, A. L., Fridman, G., Douglas, R. M., Alam, N. M. & Latham, P. Ruling out and ruling in neural codes. Proc. Natl Acad. Sci. USA 106, 5936–5941 (2009)

    Article  ADS  CAS  Google Scholar 

  26. VanRullen, R., Guyonneau, R. & Thorpe, S. J. Spike times make sense. Trends Neurosci. 28, 1–4 (2005)

    Article  CAS  Google Scholar 

  27. Curtis, J. C. & Kleinfeld, D. Phase-to-rate transformations encode touch in cortical neurons of a scanning sensorimotor system. Nature Neurosci. 12, 492–501 (2009)

    Article  CAS  Google Scholar 

  28. Montemurro, M. A., Rasch, M. J., Murayama, Y., Logothetis, N. K. & Panzeri, S. Phase-of-firing coding of natural visual stimuli in primary visual cortex. Curr. Biol. 18, 375–380 (2008)

    Article  CAS  Google Scholar 

  29. Grosmaitre, X., Santarelli, L. C., Tan, J., Luo, M. & Ma, M. Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors. Nature Neurosci. 10, 348–354 (2007)

    Article  CAS  Google Scholar 

  30. 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)

    Article  CAS  Google Scholar 

  31. Bunting, M., Bernstein, K. E., Greer, J. M., Capecchi, M. R. & Thomas, K. R. Targeting genes for self-excision in the germ line. Genes Dev. 13, 1524–1528 (1999)

    Article  CAS  Google Scholar 

  32. Rinberg, D., Koulakov, A. & Gelperin, A. Sparse odor coding in awake behaving mice. J. Neurosci. 26, 8857–8865 (2006)

    Article  CAS  Google Scholar 

  33. Garthwaite, P. H., Jolliffe, I. T. & Jones, B. Statistical Inference (Oxford Univ. Press, 2002)

    MATH  Google Scholar 

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We thank L. Doglio and the Transgenic and Targeted Mutagenesis Laboratory at Northwestern University for generation of chimaeric mice, B. Weiland for technical help with cloning and gene targeting, D. Huber, D. O'Connor and T. Komiyama for advice on mouse behaviour, D. Wesson and M. Wachowiak for instruction on sniff measurement, J. Nunez-Iglesias for assistance with statistics, G. Shtengel for advice on laser set-up, and T. Tabachnik and H. Davidowitz for help designing the behavioural rig. J. Osborne fabricated the microdrive. G. Lott provided digital acquisition software. A. Koulakov contributed to spike-sorting and classification algorithms. We thank W. Denk, K. Svoboda, R. Gütig, R. Egnor, M. Orger and A. Resulaj for comments on the manuscript. This work was supported by the Visiting Scientist Program at JFRC. T.B. was supported by NIDCD (R01DC009640, R21DC010911), the Whitehall Foundation and the Brain Research Foundation.

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Authors and Affiliations



M.S. and D.R. designed the study and build the experimental set-up, M.S. performed the experiments and analysed the behavioural data. R.S. and M.S. performed the electrophysiological recordings, R.S. and D.R. analysed the electrophysiological data, and T.B. initiated the transgenic approach and generated the gene-targeted mice. R.O. developed the laser optics and optical fibre design. M.S., T.B. and D.R wrote the manuscript. D.R. and T.B. supervised the project.

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Correspondence to Thomas Bozza or Dmitry Rinberg.

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Smear, M., Shusterman, R., O’Connor, R. et al. Perception of sniff phase in mouse olfaction. Nature 479, 397–400 (2011).

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