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

IF 4.8 2区医学 Q1 NEUROSCIENCES Neurophotonics Pub Date : 2024-04-01 Epub Date: 2024-03-06 DOI:10.1117/1.NPh.11.2.021005

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

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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.

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由 FRET 修饰生物发光驱动的单分子高效光学和化学控制。

意义：生物发光光遗传学（BL-OG）提供了一种独特而强大的方法，利用单个致动器分子（LuMinOpsin，LMO）通过光遗传学和化学遗传学操纵神经活动：方法：我们开发了新型荧光素酶，当与荧光蛋白 mNeonGreen 融合时，可优化佛尔斯特共振能量转移，从而产生与 Volvox Channelrhodopsin 1 (VChR1) 光谱调谐的明亮生物发光（BL）发射器：结果：与以前的变体和其他新变体相比，这种方法产生的新 LMO（LMO7）显示出明显更强的 BL 驱动的眼动素激活。我们对 LMO7 与 LMO3（当前标准）进行了广泛的基准测试，发现 LMO7 对体内外神经元活动的调节明显更强，对行为的调节也更有效：我们报告了一种在单个致动器中实现多种控制模式的强大新选择，以及一种可持续改进 BL-OG 的有前途的工程策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurophotonics Neuroscience-Neuroscience (miscellaneous)

CiteScore

7.20

自引率

11.30%

发文量

114

审稿时长

21 weeks

期刊介绍： At the interface of optics and neuroscience, Neurophotonics is a peer-reviewed journal that covers advances in optical technology applicable to study of the brain and their impact on the basic and clinical neuroscience applications.