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.

Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice


Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions1,2,3,4,5,6. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain7,8. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2)9 specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials10,11,12,13 at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.

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

Access options

Rent or buy this article

Prices vary by article type



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

Figure 1: ChR2-assisted photostimulation of layer 2/3 barrel cortex neurons in vivo.
Figure 2: Photostimulation in freely moving mice performing a detection task.
Figure 3: Behavioural detection of photostimulation.

Similar content being viewed by others


  1. Penfield, W. & Boldery, P. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60, 389–443 (1937)

    Article  Google Scholar 

  2. Salzman, C. D., Britten, K. H. & Newsome, W. T. Cortical microstimulation influences perceptual judgements of motion direction. Nature 346, 174–177 (1990)

    Article  ADS  CAS  Google Scholar 

  3. Romo, R., Hernandez, A., Zainos, A. & Salinas, E. Somatosensory discrimination based on cortical microstimulation. Nature 392, 387–390 (1998)

    Article  ADS  CAS  Google Scholar 

  4. Libet, B. in Handbook of Sensory Physiology (ed. Iggo, A.) 743–790 (Springer, Berlin, 1973)

    Google Scholar 

  5. Leal-Campanario, R., Delgado-Garcia, J. M. & Gruart, A. Microstimulation of the somatosensory cortex can substitute for vibrissa stimulation during Pavlovian conditioning. Proc. Natl Acad. Sci. USA 103, 10052–10057 (2006)

    Article  ADS  CAS  Google Scholar 

  6. Butovas, S. & Schwarz, C. Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex. Eur. J. Neurosci. 25, 2161–2169 (2007)

    Article  Google Scholar 

  7. Tehovnik, E. J. Electrical stimulation of neural tissue to evoke behavioral responses. J. Neurosci. Methods 65, 1–17 (1996)

    Article  CAS  Google Scholar 

  8. Ranck, J. B. Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res. 98, 417–440 (1975)

    Article  Google Scholar 

  9. Nagel, G. et al. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc. Natl Acad. Sci. USA 100, 13940–13945 (2003)

    Article  ADS  CAS  Google Scholar 

  10. 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 

  11. Li, X. et al. Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc. Natl Acad. Sci. USA 102, 17816–17821 (2005)

    Article  ADS  CAS  Google Scholar 

  12. Ishizuka, T., Kakuda, M., Araki, R. & Yawo, H. Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels. Neurosci. Res. 54, 85–94 (2006)

    Article  CAS  Google Scholar 

  13. Bi, A. et al. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50, 23–33 (2006)

    Article  CAS  Google Scholar 

  14. Hatanaka, Y., Hisanaga, S., Heizmann, C. W. & Murakami, F. Distinct migratory behavior of early- and late-born neurons derived from the cortical ventricular zone. J. Comp. Neurol. 479, 1–14 (2004)

    Article  Google Scholar 

  15. Petreanu, L., Huber, D., Sobczyk, A. & Svoboda, K. Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections. Nature Neurosci. 10, 663–668 (2007)

    Article  CAS  Google Scholar 

  16. Margrie, T. W. et al. Targeted whole-cell recordings in the mammalian brain in vivo . Neuron 39, 911–918 (2003)

    Article  CAS  Google Scholar 

  17. Fee, M. S., Mitra, P. P. & Kleinfeld, D. Central versus peripheral determinants of patterned spike activity in rat vibrissa cortex during whisking. J. Neurophysiol. 78, 1144–1149 (1997)

    Article  CAS  Google Scholar 

  18. Arenkiel, B. R. et al. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54, 205–218 (2007)

    Article  CAS  Google Scholar 

  19. Gray, N. W., Weimer, R. M., Bureau, I. & Svoboda, K. Rapid redistribution of synaptic PSD-95 in the neocortex in vivo . PLoS Biol. 4, e370 (2006)

    Article  Google Scholar 

  20. DeWeese, M. R., Wehr, M. & Zador, A. M. Binary spiking in auditory cortex. J. Neurosci. 23, 7940–7949 (2003)

    Article  CAS  Google Scholar 

  21. Petersen, R. S., Panzeri, S. & Diamond, M. E. Population coding in somatosensory cortex. Curr. Opin. Neurobiol. 12, 441–447 (2002)

    Article  CAS  Google Scholar 

  22. Ferezou, I., Bolea, S. & Petersen, C. C. Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice. Neuron 50, 617–629 (2006)

    Article  CAS  Google Scholar 

  23. Zhang, Y. P. & Oertner, T. G. Optical induction of synaptic plasticity using a light-sensitive channel. Nature Methods 4, 139–141 (2006)

    Article  Google Scholar 

  24. Nagel, G. et al. Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr. Biol. 15, 2279–2284 (2005)

    Article  MathSciNet  CAS  Google Scholar 

  25. Wang, H. et al. High-speed mapping of synaptic connectivity using photostimulation in channelrhodopsin-2 transgenic mice. Proc. Natl Acad. Sci. USA 104, 8143–8148 (2007)

    Article  ADS  CAS  Google Scholar 

  26. Schroll, C. et al. Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae. Curr. Biol. 16, 1741–1747 (2006)

    Article  CAS  Google Scholar 

  27. Lima, S. Q. & Miesenbock, G. Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121, 141–152 (2005)

    Article  CAS  Google Scholar 

  28. Salzman, C. D., Murasugi, C. M., Britten, K. H. & Newsome, W. T. Microstimulation in visual area MT: effects on direction discrimination performance. J. Neurosci. 12, 2331–2355 (1992)

    Article  CAS  Google Scholar 

  29. Tehovnik, E. J., Tolias, A. S., Sultan, F., Slocum, W. M. & Logothetis, N. K. Direct and indirect activation of cortical neurons by electrical microstimulation. J. Neurophysiol. 96, 512–521 (2006)

    Article  CAS  Google Scholar 

  30. Pologruto, T. A., Sabatini, B. L. & Svoboda, K. ScanImage: flexible software for operating laser-scanning microscopes. Biomed. Eng. Online 2, 13 (2003)

    Article  Google Scholar 

Download references


We thank B. Burbach, D. Flickinger, H. Kessels, D. O’Connor, T. Sato, R. Weimer and A. Zador for help with experiments, and D. O’Connor for comments on the manuscript. This work was supported by the Swiss National Science Foundation (to D.H.), the National Institutes of Health and the Howard Hughes Medical Institute.

Author Contributions D.H. and K.S. designed the experiments. D.H. performed the behavioral and in vivo physiological experiments. L.P., D.H. and K.S. performed the brain slice measurements. N.G. performed histology. S.R., T.H., Z.M. and K.S. provided advice and equipment. D.H. and K.S. wrote the paper. All authors discussed the results and commented on the manuscript.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Karel Svoboda.

Supplementary information

Supplementary Information 1

The file contains Supplementary Methods, Supplementary Figures 1-7 with Legends and Legends to Supplementary Movies 1-2. (PDF 1707 kb)

Supplementary Video 1

The file contains Supplementary Movie 1. (MOV 4116 kb)

Supplementary Video 2

The file contains Supplementary Movie 2. (MOV 4613 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Huber, D., Petreanu, L., Ghitani, N. et al. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451, 61–64 (2008).

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