Scientists Can Now Control Brains Using Noninvasive Sound Pulses
'Sonogenetics' uses sound to switch off and on genetically modified neurons. It's similar to optogenetics, but noninvasive.
Image: Nature Communications
One of the most important biological discoveries of this decade has been optogenetics, or the ability to turn genetically modified neurons on and off in the body using pulses of blue light. The problem with optogenetics is that, normally, you've got to cut a hole in the subject's skull for it to work. But a newly described proof of concept allows scientists to get the same results using an ultrasound, which essentially means that it's now possible to control an organism's brain using noninvasive sound waves.
Optogenetics has been a boon for neuroscientists, as it has allowed researchers to watch memories being formed, turn pain receptors off and on, simulate the effects of drugs, and even give mice on-demand erections. The technique has not yet been used in humans, primarily because it's so invasive. Optogenetics was named Nature's "Method of the Year" in 2010, when it was invented.
In optogenetics, specific proteins that are sensitive to ultraviolet light are introduced into a specimen's genome using targeted viruses. To switch the neurons on or off, the scientist must have physical access to the cells, which means mice (it's almost always mice) must have their skulls cut open, and often must be placed in special harnesses so the light can be targeted.
The new method, invented by Sreekanth Chalasani of the Salk Institute for Biological Studies and described in a new paper published in Nature Communications, is fittingly called sonogenetics. It should have several important advantages over optogenetics, he told me. Most obvious is the fact that sonograms are noninvasive and are able to penetrate the skin and target specific cells without harming untargeted ones.
"We speculate that the use of ultrasound as a non-invasive neuronal activator can be broadly applied to decode neural circuits in larger vertebrate brains with opaque skin and intact skulls," Chalasani wrote in the paper.
Secondly, it should be possible to turn several different groups of neurons on and off using the method, because there are more ranges of frequencies to play with when it comes to sound than there are colors of light that are sensitive to optogenetic techniques.
"Ultrasound is perfect because it goes through the skin, is not scattered, and maintains energy when it penetrates the skin," Chalasani told me. "You could imagine sticking an ultrasound cap on someone's head and using that to switch neurons on and off noninvasively."
For this to work, Chalasani had to find a protein that was sensitive to ultrasound. He found one, called TRP-4, that occurs naturally in invertebrates. He says the protein's normally detects when an invertebrate is being physically stretched or pulled.
Chalasani then took the genetic code for TRP-4 and used a virus to introduce it into C. Elegans, a nematode. Using the technique he was able to make four separate neurons sensitive to ultrasound. He was then able to switch these neurons on and off with as much accuracy as he would have had with an optogenetic approach. In the nematode, he used microbubbles to amplify the sound, because nematodes are so small.
In one instance, Chalasani was able to induce the nematode to turn around using ultrasound pulses. He is now working on transfecting mice with TRP-4 and hopes to replicate the experiment in them shortly.
TRP-4 is not believed to occur in mice, humans, or other vertebrates, but that doesn't mean the technique wouldn't work on us.
"The mice genome doesn't have a homologue, but if you put the gene in the mouse genome, it will make that protein," he said.
It's probably far too early to talk seriously about potential applications in humans, but let's do it anyway. Chalasani told me it's possible that an optogenetic approach in humans could be used to switch off and on neurons responsible for some of the worst symptoms of Parkinson's Disease, but no scientist has tried it, particularly because the method is so invasive. With sonogenetics, that problem would be eliminated.
"Doctors want to do deep brain stimulations of Parkinson's patients, but you have to stick an electrode in and allow it to periodically discharge—this is very dangerous and difficult to do," Chalasani said. "But if you can target the gene using one of these viruses and deliver the sonogenetic gene to that population, you could put a cap on the person's head and do it that way."
Optogenetics isn't going away anytime soon, and it does do several things better than sonogenetics. For one, light has the advantage it always does over sound: It's faster.
"The ion channels that respond to light are working much faster than the channels responding to ultrasound," he said. "If you're working on the cortex of a human brain, working on a scale of a tenth of a second, optogenetics is going to do better. I think these will be complementary techniques."
Chalasani said that ultrasounds are good at penetrating the brain but can't travel very far through air, which means that, in case you were wondering, no, it will not be possible to control a person's brain from, say, across the room. Nor will government scientists be able to brainwash you with sonogenetic commands from giant speakers in some sort of dystopian scenario. Instead, for the time being at least, the ultrasound will need to be, more or less, in contact with the skin.
So, that's probably a good thing. It's early days, but optogenetics was only invented five years ago, and now it's everywhere. If sonogenetics can be translated to mammals, it seems like it'll inevitably take off.