From channelrhodopsins to optogenetics

We did not expect that research on the molecular mechanism of algal phototaxis or archaeal light‐driven ion transport might interest readers of a medical journal when we conceived and performed our experiments a decade ago. On the other hand, it did not escape our attention that channelrhodopsin is helping an ever‐increasing number of researchers to address their specific questions. For example, the channelrhodopsin approach is used to study the molecular events during the induction of synaptic plasticity or 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 current applications have been summarized in a number of recent reviews (Fenno et al, 2011; Yizhar et al, 2011; Zhang et al, 2011). Here, we give personal insight into the history of the discovery of channelrhodopsin and a biophysical perspective on this remarkable class of proteins that has been the main topic of our research since the 1990s. The discovery of channelrhodopsin is based on two quite different research fields, studies on living algae and experiments on reconstituted microbial rhodopsins. A number of researchers have characterized the swimming behaviour and light responses of motile microalgae over at least 140 years (Fig 1A). Early studies on green microalgae root back to L.G. Treviranus (Treviranus, 1817) and behavioural responses were described by A. Famintzin from St. Petersburg University in 1878 (Famintzin, 1878). During helical swimming of the green alga Chlamydomonas , its orange eye signals to the flagella to alter the flagellar beating plane (Mast, 1916). Researchers at Stanford University implicated Mg2+ and Ca2+ in the behavioural responses and identified the role of Ca2+ influx in flagellar beat frequency changes (Halldal, 1957, Schmidt & Eckert, 1976).