Optogenetics is still a new technology with a perhaps not fully-realized potential, but it may have already gotten its first big upgrade. Whereas optogenetics relies on light, a study out of the Salk Institute has claimed to successfully replace light with sound.
Optogenetics involves modifying an organism’s genetic code so that targeted brain cells are activated (or deactivated) by light being shone upon them. When this technique was developed, it was revolutionary. It allows scientists to study regions and cells of the brain in a way that never could have been done before, and may provide therapy by activating tissues affected by disease—but it has a limitation.
If the cells need light to be controlled, the deep regions of the brain can’t be activated without surgery to implant a fiber optic cable into those areas.
Replacing light with sound
This process is costly, and may potentially cause permanent damage to the neurons the cable must pass through. So this is where the Salk Institute came in—aiming to replace light with ultrasound waves.
“In contrast to light, low-frequency ultrasound can travel through the body without any scattering,” said Sreekanth Chalasani, an assistant professor in Salk’s Molecular Neurobiology Laboratory and senior author of the study.
“This could be a big advantage when you want to stimulate a region deep in the brain without affecting other regions,” added Stuart Ibsen, a postdoctoral fellow in the Chalasani lab and co-author of the paper.
According to the study, which is published in Nature Communications, the team worked with the nematode C. elegans to try to discover a way to replace light with sound. First, they had to make sure the waves could be conveyed inside the worms, and they discovered microbubbles of gas outside of the nematodes were necessary to do this.
“The microbubbles grow and shrink in tune with the ultrasound pressure waves,” explained Ibsen. “These oscillations can then propagate noninvasively into the worm.”
Then, they discovered a membrane ion channel known as TRP-4, which opens when exposed to sound waves and activates the cell. They implanted these channels into neurons that don’t normally have them, and found that they still were reactive to ultrasound.
Wider applications
TRP-4 was only manipulated in C. elegans so far, but it could be added to any organism via genetic manipulation. If microbubbles are then injected into the bloodstream, this could allow the ultrasound waves to be transmitted into the tissue, bringing it to the neurons of interest. From there, TRP-4 would activate.
TRP-4 itself works with calcium ions, which means that its application is not limited to the brain—many other cells in the body are activated by calcium entering the cell, like in muscle tissue. However, its biggest impact will still probably be on neuroscience.
“The real prize will be to see whether this could work in a mammalian brain,” Chalasani said. (His team has already begun a study using this 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.”
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Feature Image: Salk Institute
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