The ears and tiny sensory hair cells of fish might be key to understanding, protecting, and even regenerating human hearing.
Deep inside the human ear, specialized sensory cells enable both hearing and balance. They’re called hair cells, thanks to their tufts of bristle-like cilia that line the fluid-filled cochlea of the inner ear. Sound vibrations roll through this fluid, sending ripples over the hair cells. It’s like hitting a switch; as the hair cells move or bend, electrical impulses shoot down the auditory nerve to the brain. There, the vibrations are recognized as sound.
It’s not just a human thing; all vertebrates boast hair cells in their inner ears. But fish don’t stop there. They have clusters of hair cells on their heads and down the lengths of their bodies too, called the lateral line. Those external hair cells help fish sense water movement so they can live their best fish lives: detecting prey and predators, schooling, and figuring out the direction of water flow.
And since they’re on the outside, those hair cells are a boon for researchers like Allison Coffin, associate professor in Washington State University Vancouver’s Neuroscience Program and president of the Association of Science Communicators.
“We’re really interested in understanding how these cells are damaged and then developing either preventative treatments or restorative therapies,” Coffin says.
Aging and noise exposure can damage hair cells, but so can substances like some antibiotics and chemotherapy drugs. That ototoxicity may cause hearing loss and balance issues. Thanks to external hair cells, Coffin’s team can screen drugs that may damage hair cells—or protect them from damage—by dosing tanks holding larval fish. Those five-day-old fish are each no bigger than an eyelash, so they can be anesthetized and slipped under a microscope to look for changes in the lateral line.
The lab’s primary animal model is the zebrafish. They’re related to minnows—called zebra danios by the aquarium industry—with five horizontal stripes down their sides. At first glance, it’s hard to imagine the fish have much in common with humans. But it turns out humans and zebrafish share more than 70 percent of protein-encoding genes—and zebrafish have analogs for 84 percent of genes known to cause human disease.
Over the past couple decades, scientists have tinkered with zebrafish genes to spawn thousands of zebrafish lines for research. Many carry reporter molecules like green fluorescent protein. Originally derived from a glowing jellyfish, this protein scientists can link with a zebrafish protein—like attaching a bright tag to the study subject. One line of zebrafish sports fluorescent hair cells so researchers can count them and compare drug-exposed fish with control fish. Another has glowing synapses so researchers can visualize the tiny gap where electrical and chemical signals pass between a hair cell and a nerve cell.
The goal is to identify ear-safe alternatives or protective drugs clinicians could prescribe to safeguard hair cells when using ototoxic therapies.
Zebrafish aren’t the only fish in the Coffin Lab. Just down the hall from the zebrafish setup, animals that look like overgrown tadpoles rest half-buried in gravel in two massive tanks. They’re plainfin midshipman—a type of toadfish—and they have an extraordinary feature: their hearing changes seasonally. During the breeding season, some males sing to attract mates, emitting a resonant hum that sounds like the blare of a ship horn. Their female counterparts can best hear that song for only part of the year.
Coffin has previously shown that female toadfish bulk up the numbers of hair cells in their inner ears during breeding season. Now, she wants to know if hormones like estrogen play a role in this seasonal change. That could shed light on how hearing evolved—and how hormones influence human hearing differences related to sex and age.
There’s another compelling reason to study fish: they can regenerate lost or damaged hair cells. Nestled next to each hair cell are support cells that can divide and make new hair cells as needed. That means fish and other non-mammals can lose their hearing and simply regrow it.
“That leads to a really big question: From an evolutionary perspective, what led to the loss of hair cell regeneration among mammals?” Coffin muses. “And not just hair cells. Photoreceptor cells in the retina, neurons in the brain … Mammals are lousy at regenerating stuff, but fish do it really well.”
The prevailing theory is that mammals probably sacrificed regeneration for sensitive hearing. Those support cells play specialized roles in mammal ears, making it possible to hear very soft sounds with better fine frequency resolution.
But it’s a steep cost.
Fortunately, the work in the Coffin Lab—and in the labs of her colleagues around the world—may pay off soon.
“I think we’re probably looking at a 20- to 25-year time frame for regeneration,” she says. “Whereas on the protection side, we’re starting to see some of that now—and I think we’re going to see a lot more in the next five years.”
Melissa John Mayer is a science educator and writer for WSU’s Ask Dr. Universe program.
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