Light up/wake up the brain - control of animal behavior through optogenetics

What is the connection between blue light, specific activation of neurons (nerve cells) in the brain, controlling the behavior of animals, and finding mechanisms of various neurological diseases, and possibly also treating them? The answer is optogenetics - a relatively new method that combines genetic engineering and technologies from the world of physics (such as fast and precise pulses of light, and the use of optical fibers), for the specific and precise activation of neuronal networks in the brain, using light.

What is the connection between blue light, specific activation of neurons (nerve cells) in the brain, controlling the behavior of animals, and finding mechanisms of various neurological diseases, and possibly also treating them? The answer is optogenetics - a relatively new method that combines genetic engineering and technologies from the world of physics (such as fast and precise pulses of light, and the use of optical fibers), for the specific and precise activation of neuronal networks in the brain, using light.

Let's start from the end: on 26.07.12 the results of a study were published in Current Biology magazine, in which the researchers used optogenetic methods in order to control the behavior of monkeys. The behavior in question is indeed the movement of the monkey's eyes, but it is a proof of principle that this method, which has been applied in the past in various animals, can also work in monkeys.

Neurons (nerve cells) in the brain, in general, are activated by electro-chemical changes in the cells, which allow the translation of a chemical concentration cascade (usually positively charged ions), to create an electric current (known as an action potential). In nature, this ability is usually achieved by different ion channels located in the cell membrane of the neurons, which open according to different signals. Specific control of the activation of neurons in the brain involved until recently the "bypassing" of these channels, by using electrodes, to generate the electrical signal (action potential) proactively. Today, by using genetic engineering, it is possible to control the spontaneous activation of neurons also by light. At the base of the method are proteins called opsins, which are activated in nature by a light signal. Different types of opsins exist, for example, in the eye, and enable the conversion of light into neurological electrical activity. Other opsins exist, for example, in various unicellular organisms (these are the opsins that are usually used in optogenetics). Since these are proteins encoded in the DNA of the relevant creature, opsins can be planted, by genetic engineering, even on neurons that normally should not express them. Once a neuron expresses the opsin, it can be activated by using light (in the appropriate wavelength, for example - blue light in this case).

This method has many advantages over the classic method of using electrodes: a. No need to use electrodes. There are cases where activation using the light is accessible and relatively simple. For example - in cells grown in culture, or in the tiny and transparent worm C. elegans, which is used as a model in many studies. In other cases, for example in mice or monkeys, it is of course necessary to insert the light source into the relevant area of ​​the brain (although in brain areas that are close to the surface, such as the cerebral cortex, attaching the light source to the skull may be sufficient). This is where different physical technologies come into play, such as optical fibers. B. The light can be directed to the desired place at the desired time, thus achieving more precise control over the activation (relevant for example in creatures that move during the experiment, when the light activation is external, for example in worms). third. By different manipulations of genetic engineering it is possible to determine that the opsins will be expressed only in a certain type of neurons. For example, these neurons can be specifically activated, while their neighbors are not activated (even though the light hits them all). d. By other methods of genetic engineering, it is possible to "play" with the "operating instructions". For example, it is possible to cause blue light to activate the neurons, while green light prevents their activation, and so on.

The above study was conducted as mentioned in monkeys, by researchers from the USA and Belgium, led by Wim Vanduffel. The monkeys were trained to follow with their eyes some target on the computer screen. When they activated, using light and optogenetics, certain areas of the monkeys' brains, the researchers noticed a significant improvement in tracking speed. In addition, the researchers followed the brain activity of the monkeys using fMRI, so they could see exactly which areas were activated, including those far from the stimulation area. (See link to the summary of the article at the end of the article).

I assume that at this point many of the readers imagine themselves entering the house, and next to the living room light switch, turning on the monkey's green light switch, which in response makes them coffee, or something like that. Of course, the purpose of these experiments is not to control the behavior of animals, but to promote scientific research, including the study of various diseases, and perhaps in the future even treating them. This research was preceded in recent years by many studies, which utilized this method (optogenetics) to study behavior and diseases in a wide variety of animals.

For example, using optogenetics, researchers were able to influence the movement of the tiny and transparent worm C. elegans, and even the laying of its eggs. In another study, the researchers activated a certain type of neurons in the spinal column of fish larvae, and noticed that their activation causes movements in the tail of the larva (an early developmental stage in the fish's life), which allow forward movement. These cells have been known to science for about 75 years, but until this study they did not know what their exact role was, due to the difficulty of studying them with classical methods. In studies that used optogenetics in mice, researchers were able to improve scientific knowledge about various behaviors and diseases. Starting with the study of Parkinson's disease, through feelings such as fear or hunger, to cocaine addiction, and overcoming it (see links to the abstracts of the articles at the end of the article). The continued development of optogenetic methods (which, as mentioned, only started about 6-7 years ago), and their implementation in biological research, may shed light (literally) on various neurological diseases, and perhaps even lead to the development of medical treatments for these diseases in the future.

• Link to a TED talk by Ed Boyden, one of the developers of the method (the second video on the page)
• Link to the article summary of the research in monkeys:
• links For popular science articles in English In the context of the aforementioned article (The study in monkeys):
• Link to the article summary of the research in worms (C. elegans)
• Link to the abstract of the research article on fish:
• Link to another abstract of a fish research article:
• Link to the Parkinson's study in mice:
• Link to studies on fear-memory in mice:
• Another study on fear-memory in mice
• Link to research on hunger and eating disorders:
• Link to research on drug addiction (cocaine) in mice