Researchers at the Georgia Institute of Technology have announced that, using inexpensive components from a liquid crystal display (LCD) projector, they're able to control the brain circuits in tiny laboratory animals, including freely moving worms.
This is a first in the field of optogenetics, a mix of optical and genetic techniques that has allowed researchers to probe and control genetically targeted neural circuits in laboratory animals.
Until now, the technique could be used only with larger animals by placement of an optical fiber into an animal's brain, or illumination of an animal's entire body.
But the experiments from Georgia Tech demonstrate that it is possible to control brain activity by the red, green and blue lights from a projector. The lights activate light-sensitive microbial proteins that are genetically engineered into the worms, allowing the researchers to switch neurons and muscles on and off.
"This illumination instrument significantly enhances our ability to control, alter, observe and investigate how neurons, muscles and circuits ultimately produce behavior in animals," said Hang Lu, an associate professor in the School of Chemical & Biomolecular Engineering at the Georgia Institute of Technology.
The illumination system is described in a recent edition of the journal Nature Methods. The prototype system includes a modified off-the-shelf LCD projector, which is used to cast a multi-color pattern of light onto an animal. The independent red, green and blue channels allow researchers to activate excitable cells sensitive to specific colors, while simultaneously silencing others.
"Because the central component of the illumination system is a commercially available projector, the system's cost and complexity are dramatically reduced, which we hope will enable wider adoption of this tool by the research community," explained Lu.
The researchers connected the illumination system to a microscope and combined it with video tracking, enabling them to track and record the behavior of freely moving animals, while maintaining the lighting in the intended anatomical position. When the animal moves, changes to the light's location, intensity and color can be updated in less than 40 milliseconds, according to a news release.
For their first experiment, the researchers illuminated the head of a worm (Caenorhabditis elegans) at regular intervals while the animal moved forward. This produced a coiling effect in the head and caused the worm to crawl in a triangular pattern as illustrated in the image above. To see a video of the worm's motion click here.
In another experiment, the team scanned light along the bodies of worms from head to tail, which resulted in backward movement when neurons near the head were stimulated and forward movement when neurons near the tail were stimulated.
Additional experiments showed that the intensity of the light affected a worm's behavior and that several optogenetic reagents excited at different wavelengths could be combined to control a variety of functions.
"This instrument allowed us to control defined events in defined locations at defined times in an intact biological system, allowing us to dissect animal functional circuits with greater precision and nuance," said Lu.