Scientists want to track a transparent fish’s brain in real time : NPR

A leading brain science center is making a bold move by focusing on a small, transparent fish.

The Janelia Research Campus of the Howard Hughes Medical Institute, located near Washington, D.C., has revealed its initiative to employ artificial intelligence and the unique fish, Danionella, to explore how the brain regulates complex behaviors, including social interactions.

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“It’s a big, risky bet,” says Gerry Rubin, Janelia’s founding executive director and head of biology. “But that’s what makes it interesting.”

Janelia intends to expand its facilities for fish research to 6,000 square feet, allowing for thousands of new tanks. Leaders anticipate the number of scientists working with Danionella to increase from about 10 to more than 100.

The expected outcome is significant, as observing an entire fish brain in action could provide insights into how the brain influences behavior in various species, including humans.

“We all evolved from fish, and our brains share many features of the brains of fish,” says Nelson Spruston, Janelia’s executive director.

The brain as a black box

In the quest to understand the human brain, Danionella offers distinct advantages over more commonly used lab animals like rodents.

In most species, the brain is concealed by the skull and skin, making observation challenging. However, Danionella fish have a unique advantage as they lack the upper skull portion and have transparent skin.

Despite this, Danionella is not as extensively understood as other lab models like zebrafish, which only remain transparent during their larval stage.

This is partly because Danionella cerebrum, the species favored by neuroscientists, was only recognized as a distinct species in 2021. Nonetheless, it has been gaining traction in more laboratories recently.

“Having an animal that has a clear head and a clear body [is] extremely useful for neuroscience,” says Matt Lovett-Barron, a researcher at the University of California, San Diego, studying Danionella.

From flies to fish

Janelia is renowned for its work with fruit flies, notably a 2024 project that mapped all 54.5 million connections in the insect’s brain.

Now, Janelia is ready to embark on a new, daring challenge, according to HHMI President Erin O’Shea, which could unlock one of biology’s fundamental mysteries.

This mystery, known as the brain-behavior question, seeks to understand how physical processes, like neuron firing, result in phenomena such as memory, experiences, and decision-making.

Scientists at Janelia believe that simply studying parts of an animal’s brain won’t suffice to answer this question.

“If you really want to understand how the brain is working as a whole, you really need to see all the neurons firing at once,” Rubin explains.

A transparent fish facilitates this, though it also means researchers will face three times the number of neurons compared to fruit flies.

“This is going to produce so much data that we’re going to need something like artificial intelligence to analyze it,” Rubin adds.

A new kind of science

Janelia’s strategy includes developing tools that will make it easier for scientists worldwide to study Danionella.

This involves creating a comprehensive map of every connection in the fish brain, similar to what was done for the fruit fly, and developing methods for scientists to collaborate with artificial intelligence for faster discoveries.

Currently, researchers often immobilize Danionella fish to study their brains. However, Spruston notes that Janelia’s scientists aim to change this practice.

“The ultimate goal is to do these experiments in freely swimming animals,” he says. “That’s going to require that we tackle some serious engineering challenges.”

Researchers already studying Danionella are eager for these developments.

Lovett-Barron, for instance, believes that new tools would aid in studying how the fish use visual cues to coordinate their activity while schooling.

“We place our animals into, effectively, virtual reality environments—like little video games with virtual social partners,” he explains.

This allows scientists to observe how fish brains handle the animals’ complex social dynamics.

Improved tools and methods for monitoring these brains would accelerate the research, according to Lovett-Barron.

Nevertheless, O’Shea emphasizes that answering the brain-behavior question remains a long-term objective.

“I would be ecstatic if in 10 years we [understand] just one complex behavior in the fish, like schooling,” she remarks.

Already, O’Shea notes, Janelia scientists are making progress in other areas, such as monitoring large numbers of neurons simultaneously.

They’ve successfully accomplished this with larval zebrafish, which have about 80,000 neurons, she says. Therefore, scaling up for adult Danionella fish, which have around 650,000 neurons, should be feasible.

For comparison, human brains possess approximately 86 billion neurons.