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Step-function luminopsins for bimodal prolonged neuromodulation.

Ken Berglund1, Alejandra M Fernandez1, Claire-Anne N Gutekunst1

  • 1Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia.

Journal of Neuroscience Research
|April 9, 2019
PubMed
Summary
This summary is machine-generated.

New bioluminescent optogenetic tools, step-function luminopsins (SFLMOs), enable precise neuronal control in freely behaving animals. These probes offer enhanced light sensitivity and prolonged activation, overcoming key challenges in optogenetics.

Keywords:
LEDbehaviorbioluminescencecoelenterazineopsin

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Optogenetics offers powerful neuronal control but faces challenges in light delivery and non-invasive manipulation.
  • Existing methods require invasive light sources, limiting clinical translation and chronic studies in animal models.

Purpose of the Study:

  • To develop novel opto-chemogenetic probes (luminopsins) for versatile neuronal activity manipulation.
  • To create a fusion protein combining a step-function channelrhodopsin with luciferase for bioluminescence-driven optogenetics.

Main Methods:

  • Constructed a step-function luminopsin (SFLMO) by fusing Chlamydomonas channelrhodopsin 2 with mutations to a luciferase.
  • Utilized bioluminescence resonance energy transfer (BRET) for efficient channel activation.
  • Administered SFLMOs via viral vectors in rat substantia nigra and assessed behavioral responses.

Main Results:

  • SFLMOs demonstrated prolonged photocurrents exceeding bioluminescence duration due to slow channel deactivation.
  • High light sensitivity enabled efficient activation of cell-surface channels.
  • In vivo studies showed SFLMOs elicited circling behavior in rats upon substrate injection, similar to fiber-optic stimulation.

Conclusions:

  • SFLMOs represent a significant advancement in optogenetics, offering non-invasive, chronic, and precise neuronal control.
  • These tools enhance the practicality and versatility of optogenetics in freely behaving animals.
  • SFLMOs expand the toolkit for neuroscience research and potential therapeutic applications.