New faculty member wants to know how flies make decisions

Fruit flies are not known for their sense of direction. Even among animals with tiny brains, they are particularly prone to sudden, sharp changes of direction and circuitous navigation. But their abrupt movements are not accidental. Understanding how they decide when to veer right or left is important not only for protecting bananas, but it may ultimately lead to insights into how other organisms, including humans, make complex behavioral decisions.

Gaby Maimon, who has been appointed Rockefeller’s newest assistant professor and will open the Laboratory of Integrative Brain Function on January 1, has developed a unique system for studying the neural basis for decision-making in the fruit fly, Drosophila melanogaster. Using fluorescence microscopy and glass capillaries pulled to ultrafine tips, Maimon has been able to record the electrical activity of specific neurons in the fly brain as it flies. The setup allows him to understand what’s going on in the brain as the fly is exposed to — and reacts to — various stimuli.

Pinpointing neurons. Maimon’s technique allows him to record the activity of specific neurons as a fly reacts to visual stimuli presented on a panoramic display.

His work falls somewhere between the traditional fields of behavioral neurophysiology and behavioral genetics. “In behavioral neurophysiology,” Maimon explains, “you record electrical activity from neurons as animals perform specific tasks; in behavioral genetics you manipulate the expression of genes and look for an impact on behavior. Both fields have developed great insights, but what has been difficult is to connect how genetic manipulations affect behavior through the real-time physiology of neurons. Our system may be useful for bridging this gap.”

While others study the neural basis of behavior in mammals — Maimon himself worked with monkeys as a graduate student — Drosophila give him two advantages. First, their small, poppy-seed size brains, containing around 250,000 neurons, allow Maimon to easily and repeatedly target known neurons for study. Secondly, their short lifespans and easy genetic manipulability give him the opportunity to do experiments rapidly and approach the question of how neurons link to behavior from many different angles.

“Better understanding the neural basis of behavior in a model organism such as the fly would be a great leap forward for understanding mammalian neurobiology as well,” says Maimon. “All animals have certain needs — such as deciding when and where to move. We hope that work in flies will give us a blueprint for what it would mean to answer the same types of questions in bigger organisms. Ultimately understanding how flies control the initiation and timing of action may teach us something about how the human brain controls precisely timed behaviors like speaking and what goes wrong in disorders such as Parkinson’s disease or Huntington’s disease.”

Maimon, who was born in Israel, received his undergraduate degree from Cornell University and spent a year as a predoctoral research fellow in an NIH ethology lab before entering graduate school. As a graduate student at Harvard University, he studied neuron firing patterns in monkeys that had been trained to move their arms, either in response to external triggers or as self-timed actions. He received his Ph.D. in 2005 and moved to the California Institute of Technology as a postdoc.

It was at Caltech, in the lab of Michael Dickinson, where he developed the method for obtaining “patch-clamp” recordings of the electrical activity of neurons in behaving flies. In his technique, which took over a year to develop, the experimenter tethers a fly to a stage in order to allow for the placement of electrodes, while still giving the animal the freedom to fly in place, to walk on a treadmill or to groom. Maimon and his colleagues coax the fly into locomotion — with a puff of air, for instance — and record the activity of specific neurons as the fly decides how to react to visual stimuli presented on a panoramic display surrounding the animal.

The findings he has already made with this system include one, published earlier this year in Nature Neuroscience, which showed that neurons in the fly’s visual system are about twice as responsive during flight as they are at rest. Signals from these cells are thought to influence the flight motor system, allowing the animal to steer based on what it sees around itself.

At Rockefeller, Maimon hopes to use his methodology, along with the techniques of genetic manipulation and molecular biology, to further our understanding of the neuronal basis of behavioral choice, the neuronal basis of behavioral timing and the origin of behavioral variability — why different individuals make different decisions and why the same individuals make different decisions at different times.

“It is a pleasure to welcome Gaby to Rockefeller,” says Paul Nurse, the university’s president. “Gaby is doing fascinating work to understand how neurons are linked to behavior, and he has developed a unique and very innovative system for studying decision-making in a model organism. His research has the potential to help us understand better how and why our brains lead us to make the decisions we make.”