Optogenetics combines genetic targeting of specific cells or proteins with either optical imaging or optical control of these targets. Optogenetic techniques allow neuroscientists to read or write patterns of neuronal activity in the living brain with cellular and molecular specificity.
The key reagents in optogenetics are genetically engineered, light-responsive proteins. These proteins are encoded in DNA, introduced into tissues or whole animals by genetic manipulation, and expressed selectively in defined cell types. Two kinds of proteins perform complementary functions: Optogenetic sensors emit light in response to neuronal signals, such as synaptic impulses or action potentials. These sensor proteins make activity visible. Optogenetic actuators absorb light and cause changes in neuronal signals, such as ionic currents. These acutuator proteins make activity controllable.
Optogenetic control is a form of wireless communication in which the receiver of the wireless signal—the actuator—is fabricated from materials encoded in DNA. Each nerve cell that switches on some specified gene linked to the identity of the cell will at the same time produce an actuator protein. The activity of the cell can then be controlled, simply by turning on an external light source.
Genes that encode light-responsive proteins are found naturally in photoreceptor cells. Photoreceptors respond to light by generating electrical signals—the beginning of the process in which the brain transforms light detected by the eye into an internal representation of the visible world. Photoreceptor cells contain proteins called rhodopsins, which, when illuminated, instruct ion channels in the cell membrane to open or close.
In 2002, Gero Miesenböck’s group reported that they had transplanted the gene encoding a rhodopsin protein into neurons grown in a petri dish. By shining light on these neurons, ion channels opened and the neurons could be induced to fire. This was the beginning of optogenetic control. The subsequent molecular identification of the algal photoreceptor channelrhodopsin allowed this directly light-gated ion channel to substitute for the more complex rhodopsin-based system used in Miesenböck’s earlier work.