- November 21, 2024
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Elias Lunsford stood at the podium in front of a room full of scientists at the Society for Integrative and Comparative Biology Conference in Phoenix, Arizona, ready to share the recent findings from his research at UF’s Whitney Laboratory. The title of his talk—“How the lateral line doesn’t work”—may sound innocent enough, but that simple phrase challenges one of the classical assumptions of sensory neurobiology.
“It’s a provocative title,” he said, “but I’m hoping to change the way researchers think about how the lateral line works.”
The lateral line is a sensory system that fish use to detect changes in water flow. This system shares some characteristics with special cells in the human ear, allowing many scientists to use the fish lateral line to understand physiological and developmental properties of human balance and hearing. While the lateral line has been used in sensory biology research for decades, there are some nuances to this sensory system that haven’t yet been fully explained.
“The classical system contains specialized cells called hair cells,” Lunsford explained. These cells behave sort of like a weathervane by converting the energy from moving water to electrical signals. With hair cells, moving water bends tiny thread-like appendages sticking out from these cells, opening holes in their membranes that allows ions to flow into the cells, changing their electrical properties. Traditionally, positively charged ions (i.e. cations) are thought to elicit an ‘excitatory response’ that activates neighboring neurons and passes the signal along to the brain. These changes in the electrical potential stimulate an animal’s response to its environment.
“In the human ear, this is a closed system,” Lunsford said, meaning that the body controls the amount of cations exposed to the hair cells so there are enough to elicit an excitatory response. “In contrast, the fish lateral line is a sensory organ exposed directly to the external environment and has to interface with fluctuations of cations that could disrupt its responsiveness. Freshwater species like zebrafish deal with this problem all the time because there are not enough available cations in freshwater to activate the hair cells. It wasn’t until we considered their ecology (i.e. freshwater) that we realized that these hair cells probably do not function under the classical mechanism like inner ear hair cells.”
Lunsford’s main question is whether the fish’s sensory system follows the same rules that were established in inner ear hair cells. To answer this question, Lunsford measured ion concentrations of the area surrounding the lateral line hair cells to see if they regulate the amount of available cations, like in the inner ear. To his surprise, they do not.
The next question is how are the fish using these similar cells in a different way?
“One way to address this is to consider an outflow of negatively charged ions (i.e. anions), rather than the inflow of cations,” said Lunsford. “Losing negatively charged ions has the same effect as gaining positively charged ions—the electrochemical properties of the cell would be identical.” If the external environment fluctuates—as in water—then it may better for an animal living in that environment to rely on the more controlled conditions within its own cells to drive activation.
Sure enough, Lunsford showed that tiny amounts of calcium can trigger hair cells in zebrafish, releasing a flood of chloride ions and stimulating the changes in membrane properties and release of neurotransmitters.
“This was really fascinating,” Lunsford said, “because it contradicts how we thought these sensory cells in the lateral line have worked for decades. Our findings provide a situation, never before seen in hair cells or other mechanoreceptors, where anions drive an excitatory mechanism that triggers sensor activation and signal transduction.”
If this doesn’t seem like a big deal, consider that zebrafish are one of the primary examples scientists use to understand basic principles in neurobiology. Long-held assumptions that turn out to be wrong or incomplete can mask our understanding of physiological differences that stem from biodiversity, limiting what conclusions we are able to draw and preventing scientific progress.
“For example, in physiological experiments, it is common to bathe specimens in a ‘ringer’ solution that is similar to the salt concentrations of their body fluids, like an IV,” Lunsford explained. “This makes sense when probing neurons or cells under the skin because it keeps everything immersed in a solution similar to body fluids even after dissections. However, external structures such as lateral line hair cells are not immersed in body fluids and therefore don’t need a ‘ringer’ solution to stay healthy, yet it has been a common practice. By doing this, we may inadvertently mask the mechanotransduction process that would occur in freshwater where these sensors naturally evolved and where ion concentrations are much lower.”
“These results upend a long-standing assumption in hair cell sensory biology, which has important implications ranging from human hearing to fish migration,” said Dr. James Liao, the principal investigator supervising Lunsford’s research. “This work will change the way hair cell physiology is interpreted and add a critical missing link to our understanding of the lateral line system in fishes. Only by framing the question in the natural history of the animal were we able to see what others previously overlooked.”
“This is not just relevant to fishes or even just hair cells. Our findings may provide insights into unifying principles of sensory systems,” Lunsford explained. “Other systems, such as olfaction (i.e. smell), have sensors that are exposed to the external environment and may have evolved similar mechanisms as the fish lateral line, a possibility that has been largely ignored because of long-standing assumptions.”
Lunsford’s talk, which was awarded the Best Student Presentation for his session (Division of Neurobiology, Neuroethology and Sensory Biology), lays the foundation for expanding research in sensory biology.
“With new fundamental insights come wide open vistas,” said Dr. Liao. “We have plans to dig deeper into the cellular mechanism of this phenomenon, as well as investigate the ecological implications of this work, as when some fish like salmon migrate from saltwater to freshwater.”
