In a first, researchers from Salk Institute for Biological Studies in California, led by an Indian-American researcher, have for the first time developed a way to selectively and noninvasively activate brain, heart, muscle and other cells using ultrasonic waves.
The new technique, dubbed sonogenetics, has some similarities to the burgeoning use of light to activate cells in order to better understand the brain.
This new method – which uses the same type of waves used in medical sonograms – may have advantages over the light-based approach – known as optogenetics – particularly when it comes to adapting the technology to human therapeutics, researchers said.
“Light-based techniques are great for some uses. But this is a new, additional tool to manipulate neurons and other cells in the body,” informed ,” Sreekanth Chalasani, assistant professor in Salk’s molecular neurobiology laboratory.
In optogenetics, researchers add light-sensitive 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.
Chalasani and his group decided 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,” he noted.
“This could be a big advantage when you want to stimulate a region deep in the brain without affecting other regions,” adds Stuart Ibsen, post-doctoral fellow in the Chalasani lab.
Chalasani and his colleagues first showed that, in the nematode Caenorhabditis elegans, microbubbles of gas outside of the worm were necessary to amplify the low-intensity ultrasound waves.
“The microbubbles grow and shrink in tune with the ultrasound pressure waves. These oscillations can then propagate noninvasively into the worm,” said Ibsen.
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.
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 TRP-4 could be added to any calcium-sensitive cell type in any organism including humans, Chalasani said.
Then, microbubbles could be injected into the bloodstream, and distributed throughout the body – an approach already used in some human imaging techniques.
“The real prize will be to see whether this could work in a mammalian brain,” Chalasani pointed out.
His group has already begun testing the approach in mice.
“When we make the leap into therapies for humans, I think we have a better shot with noninvasive sonogenetics approaches than with optogenetics,” he emphasised in a paper appeared in the journal Nature Communications.
Chalasani obtained his PhD from University of Pennsylvania. He then did his post-doctoral research in the laboratory of Dr Cori Bargmann at the Rockefeller University in New York.