Follow that Worm!

A gaggle of nematodes is about to set out on a tiny adventure in Rex Kerr’s lab. The millimeter-long worms are so extensively studied and so conveniently see-through that scientists know exactly where all 302 of their neurons are.

Kerr picks up a shallow plastic dish. “This is a plate where I put a yellow dot in the center, where I put salt,” he says. He picks up another dish where several nematodes wait in a drop of water. He gently scoops them out, depositing them on the plate. The worms slither off in all directions. Salt signals food to nematodes, so they should gradually start moving toward the dot.

“These three were all going in the wrong direction initially. That one has sort of curved around so it’s going more in the right direction,” Kerr says, pointing. “And these guys have gotten pretty close to the peak. That one has actually overshot. It’ll turn around eventually.”

He carries the plate of worms down the hall, into a room with two microscopes connected to two computers. Kerr and his team have developed a way to keep precise tabs on several worms at once. He sets the plate on a small platform, where a high-speed, high-resolution camera points down at it. The computer sitting next to the setup is running the software program they developed, called “Multi-Worm Tracker.” The software locates all seven animals and records their positions as they wander around the plate. Kerr analyzes data from their tracks, together with information about their genes to understand how the worms’ neurons guide them to food. He and visiting scholar Catharine Rankin, who developed the assays, and colleagues described the system in Nature Methods online June 5, 2011.

“The nice thing about having really quantitative worm behavior is that when you go in to ask how the neurons in the animal actually accomplish this, you have something precise that you’re trying to match. You’re not just trying to wave your hands and say, ‘They go forward and backward and stuff,’” Kerr says.

He studies nematodes with mutations in certain genes to find out how the genes affect neuron function. Losing a particular gene might make the animals unable to figure out how to travel in the direction of the salt, for example, which would show up in their movements. That can help clarify what the gene does in a normal animal.

“The reason we’re using worms is not because we care so much about worms,” Kerr says. “I want to know how organisms do what they do.” Worms are so straightforward that he thinks it’s possible to figure out how their nervous systems work. And once scientists understand these simplest-brained animals—there aren’t many organisms with fewer than 302 neurons—they may be able to apply some of the lessons to more complicated animals, too.

-- Helen Fields
HHMI Bulletin, August 2011

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