Microscopes are an indispensable scientific instrument, but they don't do much good if the object under study keeps crawling out of view. To keep things in focus, a team of scientists from Osaka University and Tohoku University led by Professor Koichi Hashimoto has developed a new robotic microscope that automatically tracks moving objects as part of a study of brain activity.

One of the bigger breakthroughs in the field of neuroscience is the development of optogenetics – the use of light to individually stimulate genetically engineered nerve cells. It provides a high degree of precision for studying the relationship between brain activity and behavior, but its application outside of tissue cultures can be a bit tricky.

A good example of this is the nematode caenorhabditis elegans. Sort of the microscopic equivalent of the lab rat, this tiny roundworm is ideal for optogenetics because it breeds quickly, is transparent, and has a simple nervous system of 302 nerves as opposed to the human brain's 100 billion. Unfortunately, working with live nematodes is a bit of bother because they move at about 0.1 mm per second, so they can crawl out of a microscope's field of view in less than a second.

To keep track of the annoying worms, the Tohoku team developed a robotic microscope called OSaCaBeN (OSB). Using a technique called "projection mapping," it transmits light through a series of lens and beam splitters to illuminate the nematode with different colors and infrared light. This allows the system to use pattern recognition to identify and track the head of the worm within ±0.001 mm by continually adjusting the motorized stage that the specimen sits on.

Diagram showing how the microscope tracks and stimulates the worm's nervous system(Credit: Tohoku University)

In addition to keeping the nematode in view, the system also allows the scope to track and focus on individual nerve cells and to stimulate them using a fine beam of light. According to the team, this is the only robotic microscope that can carry out both tasks at once.

"Although such a process of image identification usually takes several hours, the robot scope does it 200 times per second," says Hashimoto. "This allows us to optically measure the continuous activities of multiple nerve cells in a worm's brain as it is moving."

The team is currently using the microscope to study dopamine, which regulates the movement, emotions, and motivations of animal brains. Future studies will expand its application to other simple animals, such as zebrafish.

The research is published in Nature.

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