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Author Notes:

Email Address: Robert E. Gross : rgross@emory.edu

J.K.T., C.-A.G. and R.E.G. designed experiments. J.K.T. conducted experiments and analyzed data.

C.-A.G. performed surgeries on animals for rotation experiments.

J.K.T., C.-A.G. and R.E.G. wrote the manuscript.

The authors would like to thank Drs. Ken Berglund, Ute Hochgeschwender, Steve Potter, Ling Wei, Shan Ping Yu, and Shawn Hochman for their helpful feedback and guidance.

Special thanks to Drs. Neal Laxpati, Ming-fai Fong, and Jon Newman, Aida Risman, the Emory viral vector core, and the rest of the Gross lab for their technical support.

Subjects:

Research Funding:

NS079268 and NS079757 to R.E.G., NS086433 to J.K.T.

Inhibitory luminopsins: genetically-encoded bioluminescent opsins for versatile, scalable, and hardware-independent optogenetic inhibition

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 5

Publisher:

, Pages 14366-14366

Type of Work:

Article | Final Publisher PDF

Abstract:

Optogenetic techniques provide an unprecedented ability to precisely manipulate neural activity in the context of complex neural circuitry. Although the toolbox of optogenetic probes continues to expand at a rapid pace with more efficient and responsive reagents, hardware-based light delivery is still a major hurdle that limits its practical use in vivo. We have bypassed the challenges of external light delivery by directly coupling a bioluminescent light source (a genetically encoded luciferase) to an inhibitory opsin, which we term an inhibitory luminopsin (iLMO). iLMO was shown to suppress action potential firing and synchronous bursting activity in vitro in response to both external light and luciferase substrate. iLMO was further shown to suppress single-unit firing rate and local field potentials in the hippocampus of anesthetized rats. Finally, expression of iLMO was scaled up to multiple structures of the basal ganglia to modulate rotational behavior of freely moving animals in a hardware-independent fashion. This novel class of optogenetic probes demonstrates how non-invasive inhibition of neural activity can be achieved, which adds to the versatility, scalability, and practicality of optogenetic applications in freely behaving animals.

Copyright information:

© 2015, Macmillan Publishers Limited

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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