Scientists at the Salk Institute of Biological Studies have developed a new technique, they say, to selectively activate brain, heart, muscle, and other cells using ultrasonic waves. Called sonogenetics, the new method, which uses the same type of sound waves used in medical sonograms, may have advantages over optogenetics, the light-based approach.
In optogenetics, researchers add lightsensitive channel proteins to neurons they wish to study. By shining a focused laser on the cells, they can selectively open these channels, either activating or silencing the target neurons. But using an optogenetics approach on cells deep in the brain is difficult: typically, researchers have to perform surgery to implant a fiber optic cable that can reach the cells. Plus, light is scattered by the brain and by other tissues in the body.
The researchers opted to see if they could develop an approach that instead relied on ultrasound waves for the activation. In contrast to light, low-frequency ultrasound can travel through the body without any scattering, they explained, which could be advantageous if you want to stimulate a region deep in the brain without affecting other regions.
How It Works
They first showed that, in the nematode Caenorhabditis elegans, microbubbles of gas outside of the worm were necessary to amplify the low-intensity ultrasound waves. Since the microbubbles grow and decrease in line with the ultrasound pressure waves, the oscillations can then propagate noninvasively into the worm. (See Figure 1)
Next, they found a membrane ion channel, TRP-4, which can respond to these waves. When mechanical deformations from the ultrasound hitting gas bubbles propagate into the worm, they cause TRP-4 channels to open up and activate the cell. Armed with that knowledge, the team tried adding the TRP-4 channel to neurons that don’t normally have it. With this approach, they successfully activated neurons that don’t usually react to ultrasound.
So far, sonogenetics has only been applied to C. elegans neurons. But, they say, TRP-4 could be added to any calcium- sensitive cell type in any organism including humans. Then, microbubbles could be injected into the bloodstream, and distributed throughout the body, which is already being used in some human imaging techniques. Ultrasound could then noninvasively reach any tissue of interest, including the brain, be amplified by the microbubbles, and activate the cells of interest through TRP-4. And many cells in the human body, they point out, can respond to the influxes of calcium caused by TRP-4.
For more information, visit www.salk.edu .