The Howard Hughes Medical Institute’s Janelia Research Campus near Washington, D.C., has announced a major initiative to use artificial intelligence and an unusual transparent fish called Danionella to understand how the brain controls complex behaviors such as social interaction.
“It’s a big, risky bet,” said Gerry Rubin, Janelia’s founding executive director and head of biology. “But that’s what makes it interesting.”
Janelia plans to triple the space dedicated to the fish to 6,000 square feet, which will make room for thousands of new tanks, Rubin said. Leaders expect the number of scientists working on Danionella to rise from about 10 to 100 or more.
The payoff, they said, will be worth it — because by watching an entire fish brain function in real time, researchers hope to learn about exactly how the brain drives behavior in other species, including humans.
“We all evolved from fish, and our brains share many features of the brains of fish,” said Nelson Spruston, Janelia’s executive director.
In most species, the brain is hidden by a skull and skin, making it hard to observe. Danionella fish, in contrast, lack the top part of their skull and have see-through skin. Danionella cerebrum, the species favored by neuroscientists, was not officially identified as a separate species until 2021.
“Having an animal that has a clear head and a clear body [is] extremely useful for neuroscience,” said Matt Lovett-Barron, a scientist who studies Danionella at the University of California, San Diego.
Janelia is famous for its work on fruit flies, especially a 2024 project that led to a map of all 54.5 million connections in the insect’s brain. Now it is time for Janelia to take on a bold new challenge, said HHMI President Erin O’Shea — one that could help solve what is known as the brain-behavior question, which asks how physical processes like the firing of a neuron can give rise to things like memory, experiences, and decision-making.
Scientists at Janelia said the question cannot be answered by just studying bits of an animal’s brain.
“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 said.
A transparent fish makes that easier, he said, but it also means researchers will be dealing with three times as many neurons as they did in fruit flies. Adult Danionella have about 650,000 neurons, leaders said, compared with about 80,000 in larval zebra fish and about 86 billion in humans.
“This is going to produce so much data that we’re going to need something like artificial intelligence to analyze it,” Rubin said.
Part of Janelia’s plan is to create a map of every connection in the fish brain, much like the one the center completed for the fruit fly. It also means developing ways for scientists to work in partnership with artificial intelligence to make discoveries more quickly, Spruston said.
Current techniques often require immobilizing Danionella fish to study their brains. Spruston said the scientists at Janelia want to change that.
“The ultimate goal is to do these experiments in freely swimming animals,” he said. “That’s going to require that we tackle some serious engineering challenges.”
Scientists already studying Danionella said they would welcome those advances. Lovett-Barron, for example, said new tools would help him study how the fish use visual information to synchronize their activity when they school.
“We place our animals into, effectively, virtual reality environments — like little video games with virtual social partners,” he said.
Better tools and techniques to monitor those brains would make the work go faster, he said.
Even then, answering the brain-behavior question is a long-term goal, O’Shea said.
“I would be ecstatic if in 10 years we [understand] just one complex behavior in the fish, like schooling,” she said.
Already, she said, Janelia scientists are making progress on other fronts, such as monitoring the activity of many neurons simultaneously. They have succeeded with larval zebra fish, which have about 80,000 neurons, she said, so it should be possible to scale up for adult Danionella fish.