A kinetic-optimized CoChR variant with enhanced high-frequency spiking fidelity.
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2022-11
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Channelrhodopsins are a promising toolset for noninvasive optical manipulation of genetically identifiable neuron populations. Existing channelrhodopsins have generally suffered from a trade-off between two desired properties: fast channel kinetics and large photocurrent. Such a trade-off hinders spatiotemporally precise optogenetic activation during both one-photon and two-photon photostimulation. Furthermore, the simultaneous use of spectrally separated genetically encoded indicators and channelrhodopsins has generally suffered from non-negligible crosstalk in photocurrent or fluorescence. These limitations have hindered crosstalk-free dual-channel experiments needed to establish relationships between multiple neural populations. Recent large-scale transcriptome sequencing revealed one potent optogenetic actuator, the channelrhodopsin from species Chloromonas oogama (CoChR), which possessed high cyan light-driven photocurrent but slow channel kinetics. We rationally designed and engineered a kinetic-optimized CoChR variant that was faster than native CoChR while maintaining large photocurrent amplitude. When expressed in cultured hippocampal pyramidal neurons, our CoChR variant improved high-frequency spiking fidelity under one-photon illumination. Our CoChR variant's blue-shifted excitation spectrum enabled simultaneous cyan photostimulation and red calcium imaging with negligible photocurrent crosstalk.
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Bi, Xiaoke, Connor Beck and Yiyang Gong (2022). A kinetic-optimized CoChR variant with enhanced high-frequency spiking fidelity. Biophysical journal, 121(21). pp. 4166–4178. 10.1016/j.bpj.2022.09.024 Retrieved from https://hdl.handle.net/10161/30672.
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Xiaoke Bi
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