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Applications of Channelrhodopsin

Channelrhodopsins can be readily expressed in excitable cells such as neurons using a variety of transfection techniques (viral transfection, electroporation, gene gun). The light-absorbing pigment retinal is present in most cells (of vertebrates) as Vitamin A. This makes depolarization of excitable cells straightforward and useful for bioengineering and neuroscience applications such as photostimulation of neurons for probing of neural circuits.  The blue-light sensitive ChR2 and the yellow light-activated chloride pump halorhodopsin together enable multiple-color optical activation and silencing of neural activity with millisecond precision. VChR1 from the colonial alga Volvox carteri absorbs maximally at 535 nm and had been used to stimulate cells with yellow light (580 nm), although photocurrents generated by VChR1 are typically very small.  However, VChR1-ChR2 hybrids have been developed using directed evolution that display maximal excitation at 560 nm, and 50% of peak absorbance at wavelengths over 600 nm.  The emerging field of controlling networks of genetically modified cells with light has been termed Optogenetics.

Using fluorescently labeled ChR2, light-stimulated axons and synapses can be identified in intact brain tissue.  This is useful to study the molecular events during the induction of synaptic plasticity.  ChR2 has been used to map long-range connections from one side of the brain to the other, and to map the spatial location of inputs on the dendritic tree of individual neurons.

The behavior of transgenic animals expressing ChR2 in subpopulations of neurons can be remote-controlled by intense blue light. This has been demonstrated in nematodes, fruit flies, zebrafish, and mice.  Visual function in blind mice can be partially restored by expressing ChR2 in inner retinal cells. In the future, ChR2 might find medical applications, e.g. in forms of retinal degeneration or for deep-brain stimulation. Optical cochlear implants have been shown to work well in animal experiments and might lead to the first application of optogenetics in human patients. In addition, transfected cultured neuronal networks can be stimulated to perform some desired behaviors for applications in robotics and control.

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