Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence

Andreas Björefeldt; Jeremy Murphy; Emmanuel L. Crespo; Gerard G. Lambert; Mansi Prakash; Ebenezer C. Ikefuama; Nina Friedman; Tariq M. Brown; Diane Lipscombe; Christopher I. Moore; Ute Hochgeschwender; Nathan C. Shaner

doi:10.1117/1.NPh.11.2.021005

6 March 2024 Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence

Andreas Björefeldt, Jeremy Murphy, Emmanuel L. Crespo, Gerard G. Lambert, Mansi Prakash, Ebenezer C. Ikefuama, Nina Friedman, Tariq M. Brown, Diane Lipscombe, Christopher I. Moore, Ute Hochgeschwender, Nathan C. Shaner

Author Affiliations +

Neurophotonics, Vol. 11, Issue 2, 021005 (March 2024). https://doi.org/10.1117/1.NPh.11.2.021005

Abstract

Significance

Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO).

Aim

To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation.

Approach

We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1).

Results

A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior.

Conclusions

We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Andreas Björefeldt, Jeremy Murphy, Emmanuel L. Crespo, Gerard G. Lambert, Mansi Prakash, Ebenezer C. Ikefuama, Nina Friedman, Tariq M. Brown, Diane Lipscombe, Christopher I. Moore, Ute Hochgeschwender, and Nathan C. Shaner "Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence," Neurophotonics 11(2), 021005 (6 March 2024). https://doi.org/10.1117/1.NPh.11.2.021005

Received: 14 November 2023; Accepted: 30 January 2024; Published: 6 March 2024

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KEYWORDS

Animals

Molecules

Optogenetics

Light emitting diodes

Bioluminescence

Electrodes

Photocurrent

Significance

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