Ann-Shyn Chiang

The standfirst of the feature “Shining new light on the brain” (Curr. Biol. (2011), 21, R831–R833) stated that optogenetic control of neurons has only been around for six years. It has now come to our attention that the fundamental concept of targeting sensitivity to light to specific neurons, so that their electrical activity could be controlled optically, was established several years before the work on which the feature focused. Specifically, Gero Miesenböck’s group, then at the Memorial Sloan-Kettering Cancer Center in New York, expressed a light-responsive combination of three proteins, namely rhodopsin, arrestin-2, and the a subunit of the corresponding G protein, in cultured neurons and showed that action potentials could be triggered by illumination (Neuron (2002), 33, 15–22). This method is more complex than the later invention based on channelrhodopsins, as it needs two helper proteins in addition to the lightsensitive rhodopsin itself. The response is also slower, as there is a diffusion step between the sensory rhodopsin and the neuronal reaction. In the following year, the same group replaced this system with ion channels gated by photochemically controlled ligands (Proc. Natl. Acad. Sci. USA (2003), 100, 1352–1357), which reduces the number of proteins needed to one, speeds up the response, and generates large photocurrents. In April 2005, four months before Deisseroth’s first publication on the channelrhodopsin method, Miesenböck’s group (then at Yale University) published the first evidence of optogenetic control in a live animal (Drosophila), using this approach with caged ATP as the light-responsive ligand that activates the ion channel (Cell (2005), 121, 141–152). In November 2004, the groups of Richard Kramer, Dirk Trauner, and Ehud Isacoff at Berkeley applied optogenetic control to silence, rather than activate neurons, using photoisomerisation of an antagonist to a potassium channel (Nat. Neurosci. (2004), 7, 1381–1386). In October 2006, a meeting review co-authored by Deisseroth, Miesenböck and others (J. Neurosci. (2006) 26, 10380–10386) coins and defines the term ‘optogenetics’.