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Spectrally distinct channelrhodopsins for two-colour optogenetic peripheral nerve stimulation

Nature Biomedical Engineeringvolume 2pages485496 (2018) | Download Citation


Technologies for peripheral nerve stimulation have conventionally relied on the anatomic placement of electrodes adjacent to subsets of sensory fibres or motor fibres that selectively target an end effector. Here, we demonstrate the use of optogenetics to directly target the innervating fibres of an end effector by relying on retrograde transfection of adeno-associated virus serotype 6 to restrict axonal opsin expression to the desired fibre targets. By using an in vivo screen in rats, we identify the first channelrhodopsins as well as a halorhodopsin that respond to red light in the peripheral nerve. Combining two channelrhodopsins with spectrally distinct activation profiles allowed us to drive opposing muscle activity via two-colour illumination of the same mixed nerve. We also show halorhodopsin-mediated reductions in electrically evoked muscle tremor spectrally optimized for deep peripheral nerves. Our non-invasive peripheral neurostimulator with targeted multi-fascicle resolution enables scientific and clinical exploration, such as motor control in paralysis, biomimetic sensation feedback for amputees and targeted inhibition of muscle tremor.

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We thank C. Towne for his assistance in crafting the motivation for this project. We thank E. Boyden for his assistance and consultation on this project. Furthermore, we thank K. Cormier, C. Condon, M. Brown, as well as the entire Koch Histology Core for their countless hours of painstaking histology efforts. In addition, we thank N. Klapoetke, O. Shemesh, K. Piatkevich, E. Revol, P. Calvaresi, C. Varela, A. Harding, M. Fahmi, C. Lee, H.-J. Suk, D. Park, M. Diaz, A. Schneider and S. Osseiran for their advice, guidance and assistance. This work was funded by the MIT Media Lab Consortium.

Author information


  1. MIT Media Lab, Center for Extreme Bionics, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Benjamin E. Maimon
    • , Shriya Srinivasan
    • , Anthony N. Zorzos
    •  & Hugh M. Herr
  2. Harvard-MIT Program in Health Sciences and Technology (HST), Massachusetts Institute of Technology, Cambridge, MA, USA

    • Benjamin E. Maimon
    •  & Shriya Srinivasan
  3. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Kaitlyn Sparks


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B.E.M. and H.M.H. contributed to idea conception, study design and data analysis. B.E.M. oversaw experiment conduction and data analysis for in vivo experiments including histology and fluence modelling. K.S. contributed to experiment conduction, data collection and histology processing. S.S. performed in vitro screen experiments along with corresponding data processing. A.N.Z. contributed to idea conception and experiment planning as well as assisted with Monte Carlo modelling. B.E.M. wrote the manuscript with all authors contributing to editing the text.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Hugh M. Herr.

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    Supplementary figures.

  2. Reporting Summary

  3. Supplementary Video 1

    Two-colour independent peripheral nerve stimulation (transdermal and exposed nerves), as well as high-frequency CsChrimson activation and JAWS tremor inhibition.

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