Kerr can measure neuron activity in live worms while they are sensing the environment. An individual worm is placed under the microscope lens and herded into a wedge-shaped chute like a sheep waiting for a vaccination. A researcher uses a setup of syringes to squirt chemicals past it—and then watches to see how neurons that have been engineered to make GCaMP3 react to, for example, a scent that the nematode associates with food.

For now, the worm has to be stuck in a chute to line up its brain just so with the laser and microscope lens. But Kerr’s dream is to be able to take a dish of free-swimming worms, “and tell the scope, ‘Follow that worm! Tell me what it’s thinking wherever it goes.’ Or tell me what that small subset of neurons is doing wherever it goes.” He’s working on a system to do this—it involves putting the dish on a platform that tracks the worm’s movement and moves the plate so the worm’s head stays centered under the lens. He already has a system that can track worms as they squirm around under a microscope (see Web Extra, “Follow that Worm”).

Kerr thinks it might be possible to learn how a worm does what it does in the next decade or so. And those lessons could be applied to understanding more complicated animals.

Moving on Up

It’s still just a worm, but Tim Harris says that’s a good start. “Learning how to build a one-story, mud building is a pretty good idea,” he says. “Then people think, ‘ok, so, mud is never going to get us to the Empire State Building. We’ve got to learn how to build using bricks and do plumbing and all that jazz.’ So that’s now another measurement problem that’s even harder.”

A fruit fly brain is a lot easier to study and less complex than a human brain, but more complicated than a worm brain. When dealing with a lot more neurons, you want more measurements. It’s possible to buy a probe from a supply company with many tiny wires on the end. Ease it into the brain and the tip of each wire records the electrical impulses around it. The probe can record data for many neurons at once, Harris says. “But, you’re still poking a stick into a brain. You’ve probably caused some damage. We’d rather have a magic microscope that could see through the brain and measure the electricity, but we don’t know how to make that.”

Instead, he’s making better probes. Along with fruit fly researcher Vivek Jayaraman, Harris and Mladen Barbic in his group have developed smaller, skinnier probes for fly brains. Because they’re 10 times narrower than commercial probes, they destroy less tissue on the way in, and the tips of the wires are tiny, suited to flies’ small neurons.

Like Kerr, Jayaraman wants to measure neuron activity in flies living in a sort of virtual reality arena. An individual fruit fly is glued by its head to a bracket and then allowed to fly or to walk on a ball, like a treadmill. Meanwhile, the researchers display moving patterns on a U-shaped bank of light-emitting diodes designed by Janelia group leader Michael Reiser. The fly sees and reacts to those patterns, trying to walk or fly toward a fixed line or fly straight when it seems the world is moving to the left.

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