Control games

Dr. Ofer Yizhar, who recently joined the neurobiology department at the institute, plans to shed light on brain activity - and not just as a metaphor. In his new laboratory, he will be able to turn on and off different types of cells in the brain, by illuminating them with a tiny beam of light.

"Even the small areas of the brain are made up of many types of cells, each of which performs different functions. In addition, each brain cell creates connections - through synapses - with thousands of other cells. These complex interrelationships make it difficult for us to reach a full understanding of the activity of the cell network in the brain," says Dr. Yizhar. "Complexity rises another level in higher brain areas. The cerebral cortex, for example, consists of networks that cover large areas and are connected to each other, and we believe that damage to this area is the source of phenomena such as autism and schizophrenia."

Dr. Yizhar deals with a relatively young scientific field, called optogenetics, which provides scientists with a new tool for direct investigation of nerve cell activity. The meaning of the name "optogenetics" is that, through targeted genetic changes made in the cells, they are made to sense light, and react to it. Until now, scientists have had many other tools for measuring brain activity, explains Dr. Yizhar, but only a few of them allowed them to precisely control the activity of the cells, as well as observe the results. He started working in the field during his post-doctoral research at Stanford University. These days he is establishing a laboratory at the Weizmann Institute, with the advanced means required to continue optogenetic research.

Two cells in the hippocampus of a mouse Two types of cells in the hippocampus of a mouse
The idea to control the activity of individual brain cells was "signed" by Francis Crick, one of the discoverers of the double helix structure of DNA. Crick, who later moved to research in the field of neurobiology, predicted in the 70s that scientists would find ways to actively control brain cells, and even suggested that this would be done through light. Over the years since then, scientists have tried to implement the idea using a number of methods. The discovery of a light-responsive protein found in a single-celled algae, in 20, gave the decisive impetus to the development of the field of optogenetics.

This protein belongs to a large family of proteins called rhodopsins, all of which are designed to absorb light. The protein rhodopsin, which is found in the algae and helps it direct its way towards the light, is unique in its way of working: when it receives light, it causes a channel to open in the cell membrane, allowing the movement of charged ions into or out of the cell. Since neurons transmit their signals using electrically charged ions that pass through similar channels, scientists thought this protein might give them the control they were looking for. Surprisingly, the algal rhodopsin protein also functions well in mammalian neurons.

The first report on a successful "marriage" between an acceleration protein and a nerve cell was published in 2005, and it was the one that determined the continuation of Dr. Yizhar's path. At that time, he was about to finish his doctoral thesis at Tel Aviv University, and was looking for an idea for his doctoral thesis. "I wanted a subject that would excite me", he says. The article on optogenetics ignited the spark he was looking for, and Dr. Yizhar embarked on post-doctoral research in the optogenetics laboratory of the head of the group that carried out the experiment, Dr. Carl Dysroth, at Stanford University.

Dr. Yezhar joined a group of young researchers that developed the "toolbox" of the young field, and proved the potential of the method. Their research gradually progressed from genetically modified neurons in vitro to genetically modified mice, in which certain cells in their brains were excited by light with the help of tiny optical fibers implanted in them. "As of today," says Dr. Yizhar, "the method has developed to the extent that allows different nerve cells to be activated using different colors of light, which allows scientists to study several types of cells at the same time." The developers of the method made it accessible to other scientists as well, and today it is used by hundreds of laboratories around the world.

In his new laboratory, Dr. Yizhar plans, among other things, to continue the research he started at Stanford University, which deals with a certain area in the frontal cortex. In this place, activity related to goal-oriented behavior and working memory takes place, but its abnormal function is linked to several psychiatric disorders. Dr. Yizhar and the group of researchers at Stanford University are testing the hypothesis that both autism and schizophrenia are related to an imbalance in the activity of two types of nerve cells involved in these neural pathways. Indeed, when optogenetic tools were used to create such an imbalance in mouse brains, behavior linked to autism was observed.

Dr. Yizhar emphasizes that the new method will not allow curing psychiatric disorders in the near future. However, it will give the researchers a powerful tool that will allow them to identify the source of the disorders, and perhaps also help them plan effective treatment methods.

personal

Dr. Ofer Yizhar grew up in Mezekrat Batia, and studied at the High School of Arts and Sciences in Jerusalem. He received a bachelor's degree from the Hebrew University in Jerusalem, and second and third degrees in neurobiology from Tel Aviv University.
He lives on the institute's campus with his wife Little, a lactation consultant, and with his three children. He devotes his free time to swimming, climbing and music.