Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation
Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous development of fusions of wild-type Gaussia...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/83769 http://hdl.handle.net/10220/39946 |
| _version_ | 1811680777157476352 |
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| author | Berglund, Ken Clissold, Kara Li, Haofang E. Wen, Lei Park, Sung Young Gleixner, Jan Klein, Marguerita E. Lu, Dongye Barter, Joseph W. Rossi, Mark A. Augustine, George James Yin, Henry H. Hochgeschwender, Ute |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Berglund, Ken Clissold, Kara Li, Haofang E. Wen, Lei Park, Sung Young Gleixner, Jan Klein, Marguerita E. Lu, Dongye Barter, Joseph W. Rossi, Mark A. Augustine, George James Yin, Henry H. Hochgeschwender, Ute |
| author_sort | Berglund, Ken |
| collection | NTU |
| description | Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous development of fusions of wild-type Gaussia luciferase with channelrhodopsin, here we expanded the utility of luminopsins by fusing bright Gaussia luciferase variants with either channelrhodopsin to excite neurons (luminescent opsin, LMO) or a proton pump to inhibit neurons (inhibitory LMO, iLMO). These improved LMOs could reliably activate or silence neurons in vitro and in vivo. Expression of the improved LMO in hippocampal circuits not only enabled mapping of synaptic activation of CA1 neurons with fine spatiotemporal resolution but also could drive rhythmic circuit excitation over a large spatiotemporal scale. Furthermore, virus-mediated expression of either LMO or iLMO in the substantia nigra in vivo produced not only the expected bidirectional control of single unit activity but also opposing effects on circling behavior in response to systemic injection of a luciferase substrate. Thus, although preserving the ability to be activated by external light sources, LMOs expand the use of optogenetics by making the same opsins accessible to noninvasive, chemogenetic control, thereby allowing the same probe to manipulate neuronal activity over a range of spatial and temporal scales. |
| first_indexed | 2024-10-01T03:30:26Z |
| format | Journal Article |
| id | ntu-10356/83769 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:30:26Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/837692022-02-16T16:29:26Z Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation Berglund, Ken Clissold, Kara Li, Haofang E. Wen, Lei Park, Sung Young Gleixner, Jan Klein, Marguerita E. Lu, Dongye Barter, Joseph W. Rossi, Mark A. Augustine, George James Yin, Henry H. Hochgeschwender, Ute Lee Kong Chian School of Medicine (LKCMedicine) Bioluminescence Neural circuitry Substantia nigra Hippocampus Luciferase Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous development of fusions of wild-type Gaussia luciferase with channelrhodopsin, here we expanded the utility of luminopsins by fusing bright Gaussia luciferase variants with either channelrhodopsin to excite neurons (luminescent opsin, LMO) or a proton pump to inhibit neurons (inhibitory LMO, iLMO). These improved LMOs could reliably activate or silence neurons in vitro and in vivo. Expression of the improved LMO in hippocampal circuits not only enabled mapping of synaptic activation of CA1 neurons with fine spatiotemporal resolution but also could drive rhythmic circuit excitation over a large spatiotemporal scale. Furthermore, virus-mediated expression of either LMO or iLMO in the substantia nigra in vivo produced not only the expected bidirectional control of single unit activity but also opposing effects on circling behavior in response to systemic injection of a luciferase substrate. Thus, although preserving the ability to be activated by external light sources, LMOs expand the use of optogenetics by making the same opsins accessible to noninvasive, chemogenetic control, thereby allowing the same probe to manipulate neuronal activity over a range of spatial and temporal scales. Accepted Version 2016-02-03T08:31:15Z 2019-12-06T15:31:39Z 2016-02-03T08:31:15Z 2019-12-06T15:31:39Z 2016 Journal Article Berglund, K., Clissold, K., Li, H. E., Wen, L., Park, S. Y., Gleixner, J., et al. (2016). Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation. Proceedings of the National Academy of Sciences of the United States of America, 113(3), 358-367. https://hdl.handle.net/10356/83769 http://hdl.handle.net/10220/39946 10.1073/pnas.1510899113 26733686 en Proceedings of the National Academy of Sciences of the United States of America © 2016 The Author(s) (Published by National Academy of Sciences).This is the author created version of a work that has been peer reviewed and accepted for publication by Proceedings of the National Academy of Sciences of the United States of America, The Author(s) (Published by National Academy of Sciences). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1073/pnas.1510899113]. 40 p. application/pdf |
| spellingShingle | Bioluminescence Neural circuitry Substantia nigra Hippocampus Luciferase Berglund, Ken Clissold, Kara Li, Haofang E. Wen, Lei Park, Sung Young Gleixner, Jan Klein, Marguerita E. Lu, Dongye Barter, Joseph W. Rossi, Mark A. Augustine, George James Yin, Henry H. Hochgeschwender, Ute Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title | Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title_full | Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title_fullStr | Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title_full_unstemmed | Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title_short | Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation |
| title_sort | luminopsins integrate opto and chemogenetics by using physical and biological light sources for opsin activation |
| topic | Bioluminescence Neural circuitry Substantia nigra Hippocampus Luciferase |
| url | https://hdl.handle.net/10356/83769 http://hdl.handle.net/10220/39946 |
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