Non-invasive activation of optogenetic actuators

Elisabeth Birkner, Ken Berglund, Marguerita E. Klein, George J. Augustine, Ute Hochgeschwender

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

12 Scopus citations

Abstract

The manipulation of genetically targeted neurons with light (optogenetics) continues to provide unprecedented avenues into studying the function of the mammalian brain. However, potential translation into the clinical arena faces a number of significant hurdles, foremost among them the need for insertion of optical fibers into the brain to deliver light to opsins expressed on neuronal membranes. In order to overcome these hardware-related problems, we have developed an alternative strategy for delivering light to opsins which does not involve fiber implants. Rather, the light is produced by a protein, luciferase, which oxidizes intravenously applied substrate, thereby emitting bioluminescence. In proof-ofprinciple studies employing a fusion protein of a light-generating luciferase to a light-sensing opsin (luminopsin), we showed that light emitted by Gaussia luciferase is indeed able to activate channelrhodopsin, allowing modulation of neuronal activity when expressed in cultured neurons. Here we assessed applicability of the concept in vivo in mice expressing luminopsins from viral vectors and from genetically engineered transgenes. The experiments demonstrate that intravenously applied substrate reaches neurons in the brain, causing the luciferase to produce bioluminescence which can be imaged in vivo, and that activation of channelrhodopsin by bioluminescence is sufficient to affect behavior. Further developments of such technology based on combining optogenetics with bioluminescence-i.e. combining lightsensing molecules with biologically produced light through luciferases-should bring optogenetics closer to clinical applications.

Original languageEnglish
Title of host publicationOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics
PublisherSPIE
ISBN (Print)9780819498410
DOIs
StatePublished - 2014
EventOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics - San Francisco, CA, United States
Duration: Feb 1 2014Feb 4 2014

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume8928
ISSN (Print)1605-7422

Conference

ConferenceOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics
Country/TerritoryUnited States
CitySan Francisco, CA
Period02/1/1402/4/14

Keywords

  • Gaussia luciferase
  • bioluminescence
  • channelrhodopsin
  • coelenterazine
  • imaging
  • in vivo
  • transgenic mice
  • viral vectors

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