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In vivo Optogenetic Stimulation of the Rodent Central Nervous System
Published on: January 15, 2015
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Non-invasive activation of optogenetic actuators
Elisabeth Birkner1, Ken Berglund2, Marguerita E Klein1
1Neurotransgenic Laboratory, Duke University, Durham, NC, USA.
Proceedings of Spie--The International Society for Optical Engineering
|December 15, 2016
Summary
Researchers developed a novel optogenetics method using bioluminescence, eliminating the need for brain implants. This technique uses light-producing proteins to activate neurons, paving the way for safer clinical applications in neuroscience.
Area of Science:
- Neuroscience
- Biotechnology
- Molecular Biology
Background:
- Optogenetics enables studying mammalian brain function by controlling genetically targeted neurons with light.
- Clinical translation of optogenetics is hindered by the need for invasive optical fiber implants to deliver light.
Purpose of the Study:
- To develop and validate an alternative, non-invasive optogenetics strategy using bioluminescence for light delivery to neurons.
- To assess the feasibility of using a fusion protein (luminopsin) of luciferase and opsin for *in vivo* neuronal modulation.
Main Methods:
- Developed a luminopsin fusion protein combining a light-generating luciferase with a light-sensing opsin.
- Administered substrate intravenously to activate luciferase-mediated bioluminescence *in vivo* in mice.
- Expressed luminopsins via viral vectors and genetic transgenes for *in vivo* experiments.
Main Results:
- Demonstrated that intravenously administered substrate reaches mouse brain neurons, enabling *in vivo* bioluminescence imaging.
- Showed that bioluminescence from Gaussia luciferase can activate channelrhodopsin in cultured neurons.
- Confirmed that bioluminescence-activated channelrhodopsin is sufficient to modulate neuronal activity and affect behavior *in vivo*.
Conclusions:
- The developed bioluminescence-based optogenetics approach bypasses the need for fiber implants, offering a non-invasive method for neuronal control.
- This technology, combining optogenetics with biologically produced light, represents a significant step towards clinical applications of optogenetics.
