Rhodopsin-Based Optogenetics: Basics and Applications

Abstract

Optogenetics has revolutionized not only neuroscience but also had an impact on muscle physiology and cell biology. Rhodopsin-based optogenetics started with the discovery of the light-gated cation channels, called channelrhodopsins. Together with the light-driven ion pumps, these channels allow light-mediated control of electrically excitable cells in culture tissue and living animals. They can be activated (depolarized) or silenced (hyperpolarized) by light with incomparably high spatiotemporal resolution. Optogenetics allows the light manipulation of cells under electrode-free conditions in a minimally invasive manner. Through modern genetic techniques, virus-induced transduction can be performed with extremely high cell specificity in tissue and living animals, allowing completely new approaches for analyzing neural networks, behavior studies, and investigations of neurodegenerative diseases. First clinical trials for the optogenetic recovery of vision are underway.This chapter provides a comprehensive description of the structure and function of the different light-gated channels and some new light-activated ion pumps. Some of them already play an essential role in optogenetics while others are supposed to become important tools for more specialized applications in the future.At the moment, a large number of publications are available concerning intrinsic mechanisms of microbial rhodopsins. Mostly they describe CrChR2 and its variants, as CrChR2 is still the most prominent optogenetic tool. Therefore, many biophysically and biochemically oriented groups contributed to the overwhelming mass of information on this unique ion channel's molecular mechanism. In this context, the function of new optogenetic tools is discussed, which is essential for rational optimization of the optogenetic approach for an eventual biomedical application. The comparison of the effectivity of ion pumps versus ion channels is discussed as well.Applications of rhodopsins-based optogenetic tools are also discussed in the chapter. Because of the enormous number of these applications in neuroscience, only exemplary studies on cell culture neural tissue, muscle physiology, and remote control of animal behavior are presented.

Keywords: Behavior; Channelrhodopsins; Microbial rhodopsins; Neuroscience; Optogenetics.