Light can now be used to control cellular function and behavior in mice as well as worms.

We were confident that light-based techniques for manipulating cell function, one of our nominees as a “method to watch” last year, would see further development and increased use in the year that followed. This confidence was well placed.

More and more investigators discovered the usefulness of the light-activated bacterial channel channelrhodopsin-2 (ChR2) for neuronal stimulation. ChR2 has proven to be well suited for mapping neuronal circuits in brain slices and in vivo, and now the use of ChR2 is quickly expanding to include behavioral studies.

Mice expressing ChR2 in the somatosensory cortex, for example, could be trained to detect brief trains of light-stimulated action potentials in ChR2-expressing neurons (Nature 451, 61–64; 2008), and in zebrafish, it was shown that a light-triggered single action potential in a somatosensory neuron could evoke an escape behavior (Curr. Biol. 18, 1133–1137; 2008).

Although use of ChR2 in the clinic is still a long way off, there was even progress on this front. Transduction of rat spinal neurons with ChR2 after spinal cord injury, followed by photostimulation, resulted in recovery of respiratory function that was retained after photostimulation ceased (J. Neurosci. 28, 11862–11870; 2008). Likewise, ChR2 expression in retinal neurons restored light sensitivity to animals with retinal degeneration (Nat. Neurosci. 11, 667–675; 2008).

All the action in the past year wasn't restricted to ChR2, though. Other light-based methods for regulating cell function saw substantial advances as well. There were improvements in the speed and flexibility with which light could be directed to defined regions in biological samples, thus improving methods for light-based uncaging of bioactive compounds. In addition, many new light-activated compounds were added to the arsenal at biologists' disposal. This included not only classical small-molecule caged compounds but a growing array of light-sensitive, protein-based tools that can be genetically targeted. Although the use of light for observation will never be overshadowed by its power to manipulate cell function, the latter use is certainly coming into its own.