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The fish will play before us

Weizmann Institute of Science scientists have developed a "virtual reality" system designed for transparent zebrafish. This system makes it possible to follow the activity of serotonin cells in the brains of the fry while they play, thus revealing the mechanism of action of this ancient nervous system

Dr. Takashi Kawashima and Dr. Mio Nonke. Photo: Weizmann Institute Spokesperson
Dr. Takashi Kawashima and Dr. Mio Nonka. Photo: Weizmann Institute Spokesperson

Computer games are not just for humans. Dr. Takashi Kawashima, a new scientist in the Department of Neurobiology at the Weizmann Institute of Science, built a virtual reality system for fish. With the help of the system, which combines microscopy methods and advanced analysis capabilities, he monitors the activity of each and every cell in the transparent brains of zebrafish, and thus sees what goes on in their heads when they "play". Its purpose is to reveal the mechanism of action of one of the ancient and vital systems in the brain - the serotonin neurotransmitter system that exists in almost every living creature with a nervous system. In doing so, he hopes to reveal, among other things, the ways in which the drugs to treat depression and anxiety work, the vast majority of which work on this system.

The "game" developed by Dr. Kawashima gives the minnows the illusion that they are swimming even though their heads are fixed for imaging under the microscope. Dr. Kawashima and his research partners developed the system while he was at the Genelia Research Campus of the Howard Hughes Medical Institute. In a study, recently published in the scientific journal Science, Dr. Kawashima and his colleagues showed how they are able to monitor the activity of nerve cells with an accuracy of milliseconds through imaging.

The system gives the minnows the illusion that they are swimming, even though their heads are fixed for imaging under the microscope."

Also in his new laboratory at the institute, Dr. Kawashima plans to investigate the serotonin system. In an article he published in the scientific journal Cell, he showed that neurons of the serotonin system control the swimming functions of fish. In humans, serotonin is a neurotransmitter associated, among other things, with the regulation of moods, and this is the reason why "selective serotonin reuptake inhibitors", such as Prozac or Cipralex (medications from the SSRI family), have been used in recent decades as antidepressants and anxiety medications. These drugs use the body's own serotonin, while recycling it in the brain, but researchers disagree about the mechanisms of action of these drugs. Also, researchers still do not know why some people do not respond to these drugs, and why it takes a period of several weeks for them to start working. "To answer these and other questions," says Dr. Kawashima, "we must first understand how the serotonin system works - how serotonin cells process information and how they communicate with other areas of the brain."

One of the reasons why the serotonin system is still not well understood is its location in the depths of the brain - a fact that makes it difficult to observe. Working with transparent zebrafish is therefore an opportunity to observe this system in detail. "Right now, we're looking at it while the fish swim. Later, we will test in the virtual reality system other behaviors related to stressful situations", says Dr. Kawashima.

At the same time as building a new version of the microscope in the virtual reality system, Dr. Kawashima is working on developing specific markers that can reveal the activity of the serotonin system. "Fish react to stress in ways similar to human behaviors - avoiding eating and losing interest in their environment," he says. Therefore, he expects that his findings will shed light on disorders such as depression, anorexia and post-traumatic stress disorder.

"I reached the 'babysitter' standard"

Dr. Takashi Kawashima and Dr. Mio Nonka. Photo: Weizmann Institute

Takashi's partner, Dr. Mio Nonka, is also a neuroscientist ("although we work in very different fields", he says). In fact, it was Mew's field of interest that led the two to the Weizmann Institute of Science. "She participated in a conference in her field, and I joined on the basis of a 'babysitter' standard - our eldest daughter was then about a year old and still nursing. The organizers of the conference initiated one-on-one lunches of veteran and young researchers, and instead of registering myself for one of the meetings, I joined Mio and her partner for the meal - Prof. Alon Chen (at the time head of the neurobiology department and now the elected president of the institute). He asked me about my work, was very interested, and from there I sent him a CV. The next day he and his colleagues invited me to an interview at the institute."

Mew, who focuses on another area of ​​the brain - the amygdala - works in Prof. Orly Reiner's laboratory. Takashi and Mio, who had time to live in the United States, Europe and Japan, are beginning to feel at home in Israel - despite the language difficulties and cultural differences. "The weather and the food are great, the childcare is excellent (for a couple with two daughters), and helping each other is part of the culture here," says Takashi. "I also appreciate the fact that people tend to say what they think. People are surprised to find out that my basic tendency is quite 'Israeli', in that I also say what I think. I believe it will help me get by here at the institute."

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