A New Toy for the Optical Crowd

Increasingly, neuroscientists are using optical techniques to study neurons in the laboratory. The latest installment in their love affair with light is the discovery of light-sensitive ion channels called channelrhodopsins. Scientists have genetically altered neurons to express a channelrhodopsin called ChR2, which was originally isolated from algae. Shining light on these neurons causes positive ions to enter the cell, which depolarizes the neurons and triggers action potentials. Targeting ChR2 to specific types of neurons has allowed researchers to control the behavior of animals with fiber-optics. The New York Times picked up on these developments and recently published a nice review of the field.

Stimulating a specific class of neurons with channelrhodopsins can reveal the role of those neurons in neural circuits. But what if researchers want to test how different types of neurons interact? This would require different types of channelrhodopsins that are sensitive to different wavelengths of light. A new finding from the laboratory of Dr. Karl Deisseroth suggests that researchers may eventually have a whole color palate of channelrhodopsins at their disposal.

The paper, published in the latest issue of Nature Neuroscience, reports the discovery of a novel channelrhodopsin (VChR1) that responds to longer wavelengths of light than ChR2. The researchers scanned a genomic database to find microbial genes that resembled those coding for known channelrhodopsins. They tested the channel’s properties in Xenopus oocytes and HEK293 cells and confirmed that it was indeed a light-gated ion channel with an excitation spectrum distinct from ChR2. Then, by driving the gene with a CAMKII promoter, the researchers were able to express the protein in neurons and show that they could trigger action potentials with light.

As I mentioned, the real goal here is to use two wavelengths of light to selectively excite two types of neurons in the same preparation. Unfortunately, there is enough overlap in the excitation spectrums of ChR2 and VChR1 to make selective stimulation difficult. However, molecular refinement may eventually yield versions of these proteins with sufficiently distinct excitation profiles. Furthermore, the paper serves as a proof-of-concept for using bioinformatic tools to discover new channelrhodopsins.

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One response to “A New Toy for the Optical Crowd

  1. I’d hold off on getting all worked up about this until its demonstrated to work in vivo. Getting the sensor functionally expressed on the surface on neurons in living creatures is a much higher bar. That said, mining the Sargasso Sea sequencing data for new ChRs is a great idea. Nature has probably already invented the tool that will work. If not, DNA shuffling of the library of ChR variants could make it work.

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