Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/83769
Title: Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation
Authors: 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
Keywords: Bioluminescence
Neural circuitry
Substantia nigra
Hippocampus
Luciferase
Issue Date: 2016
Source: 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.
Series/Report no.: Proceedings of the National Academy of Sciences of the United States of America
Abstract: 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.
URI: https://hdl.handle.net/10356/83769
http://hdl.handle.net/10220/39946
DOI: 10.1073/pnas.1510899113
Rights: © 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].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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