New methods using light to control cellular activity promise to illuminate hidden biology.
Light is great for looking at things, but it can also be used to alter molecules and by extension control cellular activity. In 2005 a collaboration between the laboratories of Georg Nagel and Karl Deisseroth showed that a light-activated bacterial channel called channel rhodopsin 2 (ChR2) could be used for activation of neuronal signaling. The performance and apparent ease with which the method could be implemented generated great interest among neuroscientists.
A beam of light can control the activity of a worm expressing a light-activated protein.
By expressing ChR2 in neurons and illuminating the cells with light, researchers can now depolarize neurons at will and precisely control the spiking behavior that underlies neuronal signaling.
In 2007, the same groups improved on their earlier feat by describing a new light-activated channel that hyperpolarizes cells to inhibit neuronal signaling. They successfully used the two channels in parallel to stimulate and inhibit neuronal signaling in vivo. In a separate effort the Nagel group described a photoactivatable adenylyl cyclase, extending the technique to a new signaling pathway.
Although these papers stimulated great interest in the use of light to control cellular signaling, they were not the first such reports. Photostimulation methods have been around for years. One of the oldest, photo-uncaging, relies on the light-activated release of bioactive compounds from 'caged' compounds inactivated by a light-responsive chemical modification. This is a powerful technique, but it relies on exogenously applied synthesized molecules and cannot take advantage of the myriad of genetic techniques for modifying cells and whole organisms.
Prior to ChR2 there were several other efforts to develop protein-based photostimulation methods. These met with some success but did not generate the groundswell of interest necessary to change the way people performed experiments.
Rapid development of ChR2-based applications by multiple groups has been instrumental in changing people's perceptions of the simplicity and utility of cellular photostimulation techniques. This high level of interest is certain to drive the development of new photo-stimulation methods and applications. It may also encourage wide use of photo-uncaging and other complementary techniques. In any case, more users will continue to adopt these methods, and the anticipated flood of reports describing biological findings has already begun.
