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

Autor: Björefeldt A; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States.; Brown University, Department of Neuroscience, Providence, Rhode Island, United States.; University of Gothenburg, Institute of Neuroscience and Physiology, Department of Physiology, Gothenburg, Sweden., Murphy J; Brown University, Department of Neuroscience, Providence, Rhode Island, United States., Crespo EL; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States.; Central Michigan University, Biochemistry, Cell, and Molecular Biology Graduate Program, Mount Pleasant, Michigan, United States., Lambert GG; University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla, California, United States., Prakash M; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States., Ikefuama EC; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States.; Central Michigan University, Neuroscience Graduate Program, Mount Pleasant, Michigan, United States., Friedman N; Brown University, Department of Neuroscience, Providence, Rhode Island, United States., Brown TM; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States., Lipscombe D; Brown University, Carney Institute for Brain Science, Providence, Rhode Island, United States., Moore CI; Brown University, Carney Institute for Brain Science, Providence, Rhode Island, United States., Hochgeschwender U; Central Michigan University, College of Medicine, Mount Pleasant, Michigan, United States.; Central Michigan University, Biochemistry, Cell, and Molecular Biology Graduate Program, Mount Pleasant, Michigan, United States.; Central Michigan University, Neuroscience Graduate Program, Mount Pleasant, Michigan, United States., Shaner NC; University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla, California, United States.
Jazyk: angličtina
Zdroj: Neurophotonics [Neurophotonics] 2024 Apr; Vol. 11 (2), pp. 021005. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1117/1.NPh.11.2.021005
Abstrakt: 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.
(© 2024 The Authors.)
Databáze: MEDLINE