Harvard Scientists Control Minds of Worms

To the extent that a worm smaller than a pinhead has a mind, Harvard scientists working at the intersection of neurobiology, computer science, physics, and optogenetics have shown that they are capable of controlling it.

A study published Sunday in Nature Methods revealed that with the use of newly designed software and precise laser technology a team, including researchers at Harvard’s Center for Brain Science, successfully induced Caenorhabditis elegans worms to perform activities such as reversing direction, changing speeds, and laying eggs.

The researchers controlled a worm’s behavior by shining a laser on specific neurons. Depending on which neuron was targeted by the laser, the worm would perform a different action.

For years, scientists have been able to observe neurons one at a time, but an understanding of how neurons work together has proved elusive.

“Up until now most experiments had to be done on immobilized worms,” said study co-author Andrew M. Leifer, a researcher in the laboratory of physics professor Aravinthan D.T. Samuel ’93.

In pursuit of a deeper understanding of neural circuits, Leifer and others began work on what they called the CoLBeRT system—Controlling Locomotion and Behavior in Real Time. The “MindControl” software Leifer developed directs light with such speed and precision that it can activate or inhibit specific neurons in a moving C. elegans worm—allowing scientists to observe the worm’s subsequent behavior.

“This is an exciting tool because it potentially allows us to go in and poke around inside the nervous system of a living organism,” Leifer said.

Joshua R. Sanes, director of the Center for Brain Science, described an understanding of the relationship between neural circuits and behavior as a “holy grail,” which could connect neurobiology and psychology.

The C. elegans worm is an ideal subject, Leifer noted, because it is transparent, easy to manipulate genetically, and has only 302 neurons. By comparison, humans have about 100 billion neurons.

In the near future, Leifer plans to explore decision-making and primitive types of learning in C. elegans.

“A basic understanding of neural circuits in simpler creatures like worms and flies may eventually help us understand the human brain,” wrote Christopher M. Fang-Yen, another author of the study who is now a bioengineering professor at the University of Pennsylvania, in an e-mail.

Assistant Professor of Chemistry, Chemical Biology, and Physics Adam E. Cohen said his lab is interested in developing optical tools to watch an impulse propagate, and that he hopes to couple the CoLBeRT technology with his own in order to work out exactly how circuits function.

“The ability to stimulate nerves is an amazing capability, but the only way to observe the effect is behavior—we’d like to know what’s going on at all those intermediate levels,” he said.

Leifer cautioned against interpreting the name of his software (MindControl) too literally—the technology only works on animals that are transparent and very small, so “there’s no need to wear a tin foil hat,” he joked.

—Staff writer Julie R. Barzilay can be reached at jbarzilay13@college.harvard.edu.

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