When it comes to brains, fruit flies are literal pinheads, having only about 100,000 total neuron cells compared to humans' one billion. "People sometimes ask me, 'Does the fly actually have a brain?'," says Stephen Huston, a junior fellow at Janelia Farm.
Not only do insects have brains, but their more simplified brains and well-characterized visual systems offer some keen advantages to neuroscientists. While it's true that the fly brain is tinier and in some aspects may operate differently from mammalian brains, Huston says, "If you want to ask the really basic question of how can you wire up neurons to compute something useful, then it doesn't matter which type of brain you study."
In fact, the fly's brain is simple enough that Huston can analyze an entire circuit—from the incoming visual information flowing through sensory neurons to the motor neurons that then control muscles to adjust head position. This circuit uses visual information to keep a fly's gaze level as it flies. (Nearly all visual animals have a similar circuit to keep the head level. In the human brain, for example, the circuit would tell a soccer goalie diving sideways for a save to tilt his head to keep his eyes level.)
Generally, neuroscientists tend to study how the brain processes sensory information coming in, or how the brain generates a motor movement going out to the body. But it is much rarer to completely characterize a circuit that processes incoming sensory information and then translates it into a behavioral response. "I'd really like to be able to link those two things. We'd like to know how the sensory system talks to the motor system." In other words, how do circuits produce behavior?
In the circuit Huston is investigating, the most direct route from eyes to muscles involves only four or five connections between individual neurons. With just a handful of neurons to study, Huston can directly observe the action of each neuron, manipulate each one, and even silence each one to see how that affects the circuit's function. Because fly neurons are individually identifiable he can track and test the exact same neuron from one fly brain to another.
Huston combines two powerful laboratory techniques to probe each part of the circuit—electrophysiology to record electrical activity from individual neurons and genetic technologies that allow him to manipulate or silence specific neurons. In addition, he will test how disrupting the normal circuit changes the behavior of the flies' head movements as the flies watch different flight simulator-type movies.
Huston says being able to marry electrophysiology with the impressive fruit fly genetic toolkit developed by other labs, including that of Janelia director Gerry Rubin, will allow him to study an entire sensory-motor circuit. "Because we monitor neural activity at such high resolution, electrophysiologists like myself tend to be control freaks—we want the ability to manipulate the brain one neuron at a time," Huston says. "Janelia is an exciting place to be because the genetic techniques being developed here are finally making these sorts of single neuron manipulations possible." Janelia's robotically-maintained fruit fly library, which houses thousands of strains, and direct access to the developers of innovative fly technologies are "game-changing" resources for this research, Huston says.
"How do neurons compute anything useful?" he asks. "With this simple fruit fly behavior and the resources here it might actually be possible to tackle that question in a lifetime."