Non-invasive activation of optogenetic actuators
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 inse...
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| 格式: | Conference Paper |
| 语言: | English |
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2014
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| 在线阅读: | https://hdl.handle.net/10356/98831 http://hdl.handle.net/10220/19617 |
| _version_ | 1826128041388015616 |
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| author | Birkner, Elisabeth Berglund, Ken Klein, Marguerita E. Augustine, George J. Hochgeschwender, Ute |
| author2 | Hirschberg, Henry |
| author_facet | Hirschberg, Henry Birkner, Elisabeth Berglund, Ken Klein, Marguerita E. Augustine, George J. Hochgeschwender, Ute |
| author_sort | Birkner, Elisabeth |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:18:24Z |
| format | Conference Paper |
| id | ntu-10356/98831 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:18:24Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/988312020-11-01T05:10:04Z Non-invasive activation of optogenetic actuators Birkner, Elisabeth Berglund, Ken Klein, Marguerita E. Augustine, George J. Hochgeschwender, Ute Hirschberg, Henry Madsen, Steen J. Jansen, E. Duco Luo, Qingming Mohanty, Samarendra K. Thakor, Nitish V. Lee Kong Chian School of Medicine (LKCMedicine) Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics DRNTU::Science::Medicine 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. Published version 2014-06-10T04:20:27Z 2019-12-06T20:00:05Z 2014-06-10T04:20:27Z 2019-12-06T20:00:05Z 2014 2014 Conference Paper Birkner, E., Berglund, K., Klein, M. E., Augustine, G. J., & Hochgeschwender, U. (2014). Non-invasive activation of optogenetic actuators. Proceedings SPIE 8928, Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics. https://hdl.handle.net/10356/98831 http://hdl.handle.net/10220/19617 10.1117/12.2044157 en © 2014 SPIE. This paper was published in Proceedings SPIE 8928, Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics and is made available as an electronic reprint (preprint) with permission of SPIE. The paper can be found at the following official DOI: [http://dx.doi.org/10.1117/12.2044157]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | DRNTU::Science::Medicine Birkner, Elisabeth Berglund, Ken Klein, Marguerita E. Augustine, George J. Hochgeschwender, Ute Non-invasive activation of optogenetic actuators |
| title | Non-invasive activation of optogenetic actuators |
| title_full | Non-invasive activation of optogenetic actuators |
| title_fullStr | Non-invasive activation of optogenetic actuators |
| title_full_unstemmed | Non-invasive activation of optogenetic actuators |
| title_short | Non-invasive activation of optogenetic actuators |
| title_sort | non invasive activation of optogenetic actuators |
| topic | DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/98831 http://hdl.handle.net/10220/19617 |
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