The following article by Peter Reuell originally appeared in the Harvard Gazette on September 25, 2012:
In the quest to understand how the brain turns sensory input into behavior, Harvard scientists have crossed a major threshold. Using precisely targeted lasers, researchers have been able to take over a tiny animal’s brain, instruct it to turn in any direction they wish, and even implant false sensory information, fooling the animal into thinking food was nearby.
As described in a Sept. 23 paper published in the journal Nature, a team made up of Sharad Ramanathan, an assistant professor of molecular and cellular biology and of applied physics; Askin Kocabas, a postdoctoral fellow in molecular and cellular biology; Ching-Han Shen,aresearch assistant in molecular and cellular biology; and Zengcai V.Guo, from the Howard Hughes Medical Institute, were able to take controlof Caenorhabditis elegans — tiny, transparent worms — by manipulating neurons in the worms’ brain.
The work, Ramanathan said, is important because, by taking control of complex behaviors in a relatively simple animal — C. elegans have just 302 neurons — researchers can understand how its nervous system functions.
“If we can understand simple nervous systems to the point ofcompletely controlling them, then it may be a possibility that we cangain a comprehensive understanding of more complex systems,” Ramanathansaid. “This gives us a framework to think about neural circuits, how tomanipulate them, which circuit to manipulate, and what activity patternsto produce in them.”
“Extremely important work in the literature has focused on ablatingneurons, or studying mutants that affect neuronal function, and mappingout the connectivity of the entire nervous system,” he added. “Most ofthese approaches have discovered neurons necessary for specific behaviorby destroying them. The question we were trying to answer was: Insteadof breaking the system to understand it, can we essentially hijack thekey neurons that are sufficient to control behavior and use theseneurons to force the animal to do what we want?”
Before Ramanathan and his team could begin to answer that question,however, they needed to overcome a number of technical challenges.
SharadRamanathan: “This gives us a framework to think about neural circuits,how to manipulate them, which circuit to manipulate, and what activitypatterns to produce in them.” (Photo by Rose Lincoln/Harvard News Office.)
Using genetic tools, researchers engineered worms whose neurons gaveoff fluorescent light, allowing them to be tracked during experiments.Researchers also altered genes in the worms that made neurons sensitiveto light, meaning they could be activated with pulses of laser light.
The largest challenges, though, came in developing the hardwarenecessary to track the worms and target the correct neuron in a fractionof a second.
“The goal is to activate only one neuron,” Ramanathan explained.“That’s challenging because the animal is moving, and the neurons aredensely packed near its head, so the challenge is to acquire an image ofthe animal, process that image, identify the neuron, track the animal,position your laser, and shoot the particular neuron — and do it all in20 milliseconds,or about 50 times a second. The engineering challenges involved seemedinsurmountable when we started. Askin Kocabas found ways to overcomethese challenges.”
The system that researchers eventually developed uses a movable tableto keep the crawling worm centered beneath a camera and laser. Theresearchers also custom-built computer hardware and software, Ramanathansaid, to ensure that the system works at the split-second speedsneeded.
The result, he said, was a system capable of controlling not only theworms’ behavior, but their senses as well. In one test described in thepaper, researchers were able to use the system to trick a worm’s braininto believing food was nearby, causing it to make a beeline toward theimaginary meal.
Read the entire article (with video) in the Harvard Gazette