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Automated light-based mapping of motor cortex by photoactivation of channelrhodopsin-2 transgenic mice

Nature Methods volume 6, pages 219–224 (2009)Cite this article

Abstract

Traditionally, mapping the motor cortex requires electrodes to stimulate the brain and define motor output pathways. Although effective, electrode-based methods are labor-intensive, potentially damaging to the cortex and can have off-target effects. As an alternative method of motor mapping, we photostimulated transgenic mice expressing the light-sensitive ion channel channelrhodopsin-2 in predominantly layer-5 output cortical neurons. We report that optical stimulation of these neurons in vivo using a stage scanning laser system resulted in muscle excitation within 10–20 ms, which can be recorded using implanted electromyogram electrodes or by a noninvasive motion sensor. This approach allowed us to make highly reproducible automated maps of the mouse forelimb and hindlimb motor cortex much faster than with previous methods. We anticipate that the approach will facilitate the study of changes in the location and properties of motor maps after skilled training or damage to the nervous system.

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Figure 1: Automated LBM of the mouse motor cortex.
Figure 2: ChR2-mediated EEG responses can be elicited from all regions of the exposed cortex.
Figure 3: High-resolution optically stimulated motor maps.
Figure 4: ICMS and LBM motor maps obtained from the same ChR2-positive mouse.
Figure 5: Motor maps are stable and repeatable.
Figure 6: Motor and sensory cortical limb representations.

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Acknowledgements

This work was supported by operating grants to T.H.M. (MOP-12675) and the In Vivo Imaging Centre from the Canadian Institutes of Health Research. We thank P. Wang, H. Erb, C. Jiang, A. Tung and N. Scott for assistance.

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Author notes

  1. Oliver G S Ayling, Thomas C Harrison and Jamie D Boyd: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Kinsmen Laboratory, 2255 Wesbrook Mall, Vancouver, V6T 1Z3, Canada

    Oliver G S Ayling, Thomas C Harrison & Timothy H Murphy

  2. Brain Research Center, 2211 Wesbrook Mall, Vancouver, V6T 1Z3, Canada

    Oliver G S Ayling, Thomas C Harrison & Timothy H Murphy

  3. In Vivo Imaging Centre, 2350 Health Sciences Mall, Vancouver, V6T 1Z3, Canada

    Jamie D Boyd & Alexander Goroshkov

  4. Department of Cellular and Physiological Sciences, University of British Columbia, 2255 Wesbrook Mall, Vancouver, V6T 1Z3, Canada

    Timothy H Murphy

Authors
  1. Oliver G S Ayling
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  5. Timothy H Murphy
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Contributions

O.G.S.A. and T.C.H. collected and analyzed data, and prepared the manuscript. J.D.B. developed software, analyzed data and performed histological analyses. A.G. performed optical design and fabrication of the device. T.H.M. conceived the work, analyzed data and prepared the manuscript.

Corresponding author

Correspondence to Timothy H Murphy.

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Competing interests

O.G.S.A., T.C.H., J.D.B. and T.H.M. are listed as inventors on a US patent application that covers aspects of the work described in the manuscript.

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Supplementary Figures 1–8, Supplementary Tables 1–2, Supplementary Methods (PDF 2031 kb)

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Ayling, O., Harrison, T., Boyd, J. et al. Automated light-based mapping of motor cortex by photoactivation of channelrhodopsin-2 transgenic mice. Nat Methods 6, 219–224 (2009). https://doi.org/10.1038/nmeth.1303

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