ABSTRACT
Optogenetic technology uses light to control or modulate neuronal function, providing a means of interacting with neurons that is unchallenged in its temporal resolution, spatial resolution, and cell type specificity. First applied in mammalian neurons in 2005 (Boyden et al., 2005; Li et al., 2005), this approach comprises a single-component, genetically encoded system to activate, inhibit, or otherwise modulate the activity of neurons with light. The actuators used in optogenetic technology, essentially converting electromagnetic energy to changes in neuronal excitability, are light-sensitive proteins that serve as ion channels, pumps, or biochemical pathway modulators. These tools, typically proteins of the microbial rhodopsin family (Yizhar et al., 2011a; Zhang et al., 2011), are genetically encoded single-component actuators, which allows for selective targeting to specific cell types and therefore interrogation of individual components of highly complex neural systems. Once the targeted neuronal population expresses the genetically encoded optogenetic tool, its function can be controlled with light. In contrast with pharmacological manipulations, which suffer from diffusion of the active compound and poor temporal control, light is not subject to diffusion and can be delivered with millisecond precision. This provides exquisite experimental control that cannot be matched by other genetically encoded approaches, such as pharmacological manipulation of receptors or another genetically encoded system: designer receptors exclusively activated by designer drugs (DREADDs; Armbruster et al., 2007; Vardy et al., 2015).
