AILSA CHANG, HOST:
One of the world's top centers for brain science is taking a huge gamble on a tiny, transparent fish.
GERRY RUBIN: It's a big, risky bet, but that's what makes it interesting.
CHANG: NPR's Jon Hamilton reports on an effort to study an entire fish brain at work, which could help explain how our own brains control our behavior.
JON HAMILTON, BYLINE: The Janelia Research Campus of the Howard Hughes Medical Institute is famous for its work on fruit flies, like the ones in this sorting machine.
RUBIN: And this robot arm is picking up a vial, putting the barcode on, putting it over here.
HAMILTON: That's Gerry Rubin, a biologist who helped create this cutting-edge research center near Washington, D.C., two decades ago. In 2024, he played a key role in mapping all 54 million connections in a fruit fly's brain. Now, Ruben says, it's time for Janelia to take on a new challenge.
RUBIN: 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.
HAMILTON: Which is tough in a fruit fly because its brain is covered by an opaque shell. But Ruben thinks the feat might be possible in a transparent fish called Danionella, which has about three times as many neurons as a fruit fly.
RUBIN: This is going to produce so much data that we really need something like AI to analyze it. A human can't look at this.
HAMILTON: Ruben says, even with help from artificial intelligence, the project may fail, but Janelia is committed. Zari Zavala-Ruiz, a biochemist, shows me a dark room filled with small plastic fish tanks.
ZARI ZAVALA-RUIZ: It takes a minute to adjust your eyes, but these are our Danionella. The first time I came here, I was like, oh, there's nothing in there, until my eyes adjusted.
HAMILTON: The glass-like fish are easy to miss. Look closely, though, and you can see their eyes, their brains, their internal organs and whatever they just ate. Jim Cox is in charge of the animals at Janelia. He's expecting lots more Danionella.
JIM COX: These two rows are about 960 tanks. Those two rows are 960 tanks. They're on independent filtration systems.
HAMILTON: Part of Janelia's plan is to create tools that will make it easier for scientists everywhere to study Danionella. The species favored by brain scientists wasn't even discovered until 2021. Since then, it has begun challenging the dominance of zebrafish in brain labs. Matt Lovett-Barron of the University of California, San Diego runs a lab that is already focused on Danionella.
MATT LOVETT-BARRON: Having an animal that has a clear head and a clear body altogether makes this extremely useful for neuroscience.
HAMILTON: Lovett-Barron works with fish whose neurons have been programmed to glow when they become active.
LOVETT-BARRON, ASSISTANT PROFESSOR, UC SAN DIEGO: We place our animals into, effectively, virtual reality environments, like little video games with virtual social partners.
HAMILTON: Then the scientists watch as the fish brains manage their busy social lives. Lovett-Barron says Danionella form schools, go through courtship rituals, and the males even stake out their territory with a distinct sound.
(SOUNDBITE OF DANIONELLA CLICKING)
LOVETT-BARRON, ASSISTANT PROFESSOR, UC SAN DIEGO: It's very loud given how small they are.
HAMILTON: By watching an entire fish brain function, researchers hope to learn more about other species. Janelia's executive director, Nelson Spruston, says that includes humans.
NELSON SPRUSTON: We all evolved from fish. We're all vertebrates, and our brains share many features of the brains of fish.
HAMILTON: Right now, scientists often immobilize Danionella in order to study their brains. Spruston says the scientists at Janelia want to change that.
SPRUSTON: The ultimate goal is to actually do these experiments in freely swimming animals, and that's going to require that we tackle some serious engineering challenges to be able to do cellular-resolution microscopy in a moving animal.
HAMILTON: If the effort succeeds, it could answer one of the oldest questions in biology - how the brain controls behavior in a living animal. Erin O'Shea, the president of Howard Hughes Medical Institute, says that's a distant goal.
ERIN O'SHEA: I would be ecstatic if in 10 years we've come to some kind of real understanding just for one complex behavior in the fish.
HAMILTON: Like how lots of individual Danionella are able to form a school of fish that moves as one. Jon Hamilton, NPR News.
(SOUNDBITE OF ROWON SONG, "FOREIGN") Transcript provided by NPR, Copyright NPR.
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