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

Nature volume 451, pages 61–64 (2008)Cite this article

Abstract

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.

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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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA ,

    Daniel Huber, Leopoldo Petreanu, Nima Ghitani & Karel Svoboda

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA ,

    Daniel Huber, Leopoldo Petreanu, Sachin Ranade, Tomáš Hromádka, Zach Mainen & Karel Svoboda

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  1. Daniel Huber
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Correspondence to Karel Svoboda.

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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). https://doi.org/10.1038/nature06445

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