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Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation.

Publication ,  Journal Article
Berglund, K; Clissold, K; Li, HE; Wen, L; Park, SY; Gleixner, J; Klein, ME; Lu, D; Barter, JW; Rossi, MA; Augustine, GJ; Yin, HH; Hochgeschwender, U
Published in: Proceedings of the National Academy of Sciences of the United States of America
January 2016

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.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

January 2016

Volume

113

Issue

3

Start / End Page

E358 / E367

Related Subject Headings

  • Volvox
  • Synapses
  • Substantia Nigra
  • Rhodopsin
  • Rats, Sprague-Dawley
  • Optogenetics
  • Opsins
  • Neurons
  • Movement
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
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Berglund, K., Clissold, K., Li, H. E., Wen, L., Park, S. Y., Gleixner, J., … Hochgeschwender, U. (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), E358–E367. https://doi.org/10.1073/pnas.1510899113
Berglund, Ken, Kara Clissold, Haofang E. Li, Lei Wen, Sung Young Park, Jan Gleixner, Marguerita E. Klein, et al. “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, no. 3 (January 2016): E358–67. https://doi.org/10.1073/pnas.1510899113.
Berglund K, Clissold K, Li HE, Wen L, Park SY, Gleixner J, et al. 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. 2016 Jan;113(3):E358–67.
Berglund, Ken, et al. “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, vol. 113, no. 3, Jan. 2016, pp. E358–67. Epmc, doi:10.1073/pnas.1510899113.
Berglund K, Clissold K, Li HE, Wen L, Park SY, Gleixner J, Klein ME, Lu D, Barter JW, Rossi MA, Augustine GJ, Yin HH, Hochgeschwender U. 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. 2016 Jan;113(3):E358–E367.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

January 2016

Volume

113

Issue

3

Start / End Page

E358 / E367

Related Subject Headings

  • Volvox
  • Synapses
  • Substantia Nigra
  • Rhodopsin
  • Rats, Sprague-Dawley
  • Optogenetics
  • Opsins
  • Neurons
  • Movement
  • Mice, Inbred C57BL