Optogenetics in drosophila neuroscience

Abstract

Optogenetic techniques enable one to target specifi c neurons with light-sensitive proteins, e.g., ion channels, ion pumps, or enzymes, and to manipulate their physiological state through illumination. Such artifi cial interference with selected elements of complex neuronal circuits can help to determine causal relationships between neuronal activity and the effect on the functioning of neuronal circuits controlling animal behavior. The advantages of optogenetics can best be exploited in genetically tractable animals whose nervous systems are, on the one hand, small enough in terms of cell numbers and to a certain degree stereotypically organized, such that distinct and identifi able neurons can be targeted reproducibly. On the other hand, the neuronal circuitry and the behavioral repertoire should be complex enough to enable one to address interesting questions. The fruit fl y Drosophila melanogaster is a favorable model organism in this regard. However, the application of optogenetic tools to depolarize or hyperpolarize neurons through light-induced ionic currents has been diffi cult in adult fl ies. Only recently, several variants of Channelrhodopsin-2 (ChR2) have been introduced that provide suffi cient light sensitivity, expression, and stability to depolarize central brain neurons effi ciently in adult Drosophila. Here, we focus on the version currently providing highest photostimulation effi ciency, ChR2-XXL. We exemplify the use of this optogenetic tool by applying it to a widely used aversive olfactory learning paradigm. Optogenetic activation of a population of dopamine-releasing neurons mimics the reinforcing properties of a punitive electric shock typically used as an unconditioned stimulus. In temporal coincidence with an odor stimulus this artifi cially induced neuronal activity causes learning of the odor signal, thereby creating a light-induced memory.