**2. Optogenetics**

The sequencing of the genome in species as different as humans and plants has helped us to understand mechanisms of development, physiology, and evolution [12–14]. The field of epigenetics studies chemical modifications of the DNA as well as interactions that include genome-associated proteins to analyze differences in the expression of genes that are heritable and arise without a change of the DNA sequence. As such epigenetic mechanisms afford another mechanism of transcriptional control in regulating gene expression. While the field of epigenetics revealed an entire new layer of genetic regulation, optogenetics is the field that has allowed researchers to study cell signaling pathways and networks with unprecedented detail and resolution [15, 16]. This relatively new field exemplifies the power of taking a molecular approach to explore complex biological systems such as the brain in order to understand even the nature of emotions or psychiatric disorders [17]. Optogenetics is a combination of genetic manipulation and the use of optical tools. Genes that confer light responsiveness are inserted into cells of interest and allow for subsequent assessment of well-defined events in cells or even freely moving animals. Genetic tools allow the insertion of genes into cells that afterward respond to specific wavelengths of light. Subsequently, light can turn on or off specific signal cascades in cells and even trigger or inhibit the behavior of organisms. Thereby, optogenetics gives researchers an opportunity to obtain a deep view into an organism under optical control [18].

To understand the brain means to be able to reliably manipulate it and predict its response. Neuroscientists have long used electrophysiological techniques to stimulate particular brain areas or even single neurons [15]. Electrical stimuli activate neural circuitry, often without being able to stop neuronal activity. Neuropharmacological tools are based on drugs that are slow in their effects or not specific enough to stimulate individual cells. In 2005, a set of new techniques started to emerge that combined optical stimuli with genetic tools in order to control events in individual cells [19]. The field of optogenetics has since revolutionized experimental approaches to study cell signaling, metabolism, brain circuits, and organismal behavior.

Two pieces of information about the origin of the field are worth mentioning. As recounted by Karl Deisseroth [15], it was Nobel Laureate Francis Crick who suggested the creation of this new field in the late 1970s by stating that the major challenge facing neuroscience was the need to control one type of brain cell while leaving others unaltered. Later on, Crick proposed the use of light to achieve this control feat because it could be delivered in precisely timed pulses. The other piece of information relates to the fact that it was microorganisms that allowed optogenetics to come into existence. It had been known for many years that certain microorganisms generate proteins, which allow ions to cross the cell membrane in response to light. The genes coding for these proteins are known as opsins. One of the proteins, bacteriorhodopsin, discovered in 1971, is an ion pump that can be activated by photons of green light [20]. Later on, other opsins were identified, namely the halorhodopsins and channel rhodopsins, which are also light-gated ion pumps, more specifically, single-component light-activated cation channels. These discoveries have led to widespread use of optogenetic tools. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) are found in the model organism *Chlamydomonas reinhardtii*. In 2005, several groups published the first accounts of using ChR2 as a tool for genetically targeted optical remote control, namely optogenetics, of neurons, neural circuits, and behavior of animals [19, 21, 22]. This marked the beginning of the field of optogenetics. Optogenetics has taken advantage of microbial opsins such as channel rhodopsin to genetically target and then remotely control excitable cells. In order to control cells or organisms, optical activation is superior to other methods because of its speed, ease of use, specific targeting, and precise temporal control of optical activation.
