Cracking the code inside a worm’s brain

Christopher Fang-Yen, assistant professor in the Department of Bioengineering, studies worms.  Specifically, Caenorhabditis elegans (or C. elegans in short). These transparent, one-millimeter-long creatures have just 302 neurons, and their study allows Fang-Yen to combine his training as a physicist, optical engineer and neurobiologist.  Interested in bringing his expertise in imaging devices to biology, Fang-Yen states, “I want to develop new tools and use them to understand how neural circuits generate behavior.”

Traditionally, neurobiologists detect activity by probing an animal’s neurons to record their electrical impulses.  One limitation of this method is that in a laboratory setting the subject is not in its natural environment, but recently developed methods combining optics and genetics allow scientists to both detect and perturb neural activity in freely behaving animals.   Fang-Yen uses these methods to understand how C. elegans performs its natural behaviors such as eating, crawling, swimming, and laying eggs.

During his during his postdoctoral research at Harvard University, Fang-Yen devised experiments to record slow-motion videos (such as the one seen below, provided courtesy of Harvard’s CoLBeRT project) of the worms feeding on bacteria, and discovered for the first time exactly how it is that C. elegans eats.  Some of the worm’s critical feeding movements occur very quickly, within 10 to 20 milliseconds.  The worms extract their food (bacteria) from water and move it into a “stomach” region with a speed that is too rapid to be viewed by the naked eye. Results from the videos have shown that C. elegans is a filter feeder like a baleen whale and spits out water and keeps only the food via a series of muscular contractions. Fang-Yen is planning his future research to study how the worm’s brain encodes this complex pattern of muscle movements.

Disrupting a worm’s locomotion by inhibiting muscles with laser light from Samuel Lab on Vimeo.

Fang-Yen has also shown how C. elegans coordinates its motor behavior after studying how the worms move in different environments, for example crawling on the ground and swimming in water. This is a critical step in discovering the way neural circuits behave.  He has also invented a device that can pinpoint specific neurons while C. elegans is moving and perturb them, using lasers, a camera, and a sophisticated computer tracking system.  Fang-Yen is combining discoveries in optogenetics—changing behavior with light—with the neurobiology of worms to learn how worms make decisions and he is cracking codes of neural science that someday may someday help researchers understand the nervous systems of more complex and non-transparent creatures, such as monkeys and humans.