dc.contributor.authorBerglund, Ken
dc.contributor.authorClissold, Kara
dc.contributor.authorLi, Haofang E.
dc.contributor.authorWen, Lei
dc.contributor.authorPark, Sung Young
dc.contributor.authorGleixner, Jan
dc.contributor.authorKlein, Marguerita E.
dc.contributor.authorLu, Dongye
dc.contributor.authorBarter, Joseph W.
dc.contributor.authorRossi, Mark A.
dc.contributor.authorAugustine, George James
dc.contributor.authorYin, Henry H.
dc.contributor.authorHochgeschwender, Ute
dc.date.accessioned2016-02-03T08:31:15Z
dc.date.available2016-02-03T08:31:15Z
dc.date.issued2016
dc.identifier.citationBerglund, 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.en_US
dc.identifier.urihttp://hdl.handle.net/10220/39946
dc.description.abstractLuminopsins 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.en_US
dc.format.extent40 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.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].en_US
dc.subjectLuciferaseen_US
dc.subjectBioluminescence
dc.subjectNeural circuitry
dc.subjectSubstantia nigra
dc.subjectHippocampus
dc.titleLuminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activationen_US
dc.typeJournal Article
dc.contributor.schoolLee Kong Chian School of Medicine
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1510899113
dc.description.versionAccepted Versionen_US


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