The ability to stimulate specific neurons using beams of light, a technique known as optogenetics, has led to great advances in neuroscience over the past decade, helping to establish critical links between brain and behavior. But this approach has its drawbacks. Notably, light is easily scattered by the body’s tissues, and optogenetics requires surgery to implant a fiber optic cable in the brain of a laboratory animal—usually a mouse or rat.
New research points to a similar but less invasive method for controlling individual neurons. In a first for neuroscience, a team of researchers led by Sreekanth Chalasani, a 2012 Rita Allen Foundation Scholar and a neurobiologist at the Salk Institute for Biological Studies, successfully used low-frequency ultrasound waves to activate neurons in the millimeter-long roundworm Caenorhabditis elegans, a technique they call sonogenetics.
The team made use of the roundworm’s naturally occurring neural machinery to make neurons responsive to ultrasound signals—with just 302 neurons, this worm is a valuable model organism for studying the nervous system. A protein called TRP-4 forms channels in the worm’s nerve cell membranes. Normally, TRP-4 enables worms to sense the stretching movements of their bodies, but Chalasani and his team discovered that TRP-4 is also sensitive to ultrasound signals, similar to the sound waves often used to image fetuses or monitor heart functions in humans.
The researchers engineered specific neurons, whose action is known to cause worms to reverse their crawling direction, to produce TRP-4 membrane channels. Then, they placed the worms on an agar surface in a petri dish and added gas-filled “microbubbles” to amplify the ultrasound waves. They found that an ultrasound pulse caused a crawling worm to swiftly change its direction. Chalasani and his team published their results on September 15 in Nature Communications.
Sonogenetics is unlikely to replace optogenetics, but it may develop into another useful tool for deciphering and manipulating brain activity—perhaps even in humans. Chalasani’s group is currently testing the technique in mice.
“The real prize will be to see whether this could work in a mammalian brain,” Chalasani said in a news story announcing the findings. “When we make the leap into therapies for humans, I think we have a better shot with noninvasive sonogenetics approaches than with optogenetics.”
Update: Chalasani’s research on sonogenetics was featured in the September 29 edition of The New York Times. The digital version of the article, “Testing Neurons With Ultrasound,” includes a video with more great footage of crawling roundworms, plus a brief comparison of optogenetics and sonogenetics.
Correction (October 1): The original version of this article stated that Chalasani’s team used high-frequency ultrasound waves to active neurons in C. elegans. In fact, the researchers used low-frequency ultrasound waves.