Scientists Use Ultrasound to Activate Brain Cells

The same ultrasound technology that can reveal intricate details of a baby in utero or spot a tiny cyst on your kidney can control brain cells—at least in nematode worms—and may have applications in a variety of illnesses ranging from diabetes to Parkinson’s disease. As they detailed in a study published in Nature Communications, researchers at the Salk Institute successfully used ultrasound waves to alter how neurons behave in the brains of nematode worms, Caenorhabditis elegans. This technique, called "sonogenetics," may one day have applications for humans.

Skreekanth Chalasani, an assistant professor in molecular neurobiology at Salk, worked with a team of researchers to find a protein that would respond to sound waves the way some do to light waves—and they did just that. “We found a protein, TRP-4, that is uniquely sensitive to a low frequency of ultrasound, a channel that allows calcium ions to come through and activate the cell,” he tells mental_floss. When they surrounded the proteins with “microbubbles,” circular lipids filled with gas, the cells became even more receptive to the ultrasound because the bubbles expand and contract at the frequency of the ultrasound wave and amplify it. In other words, they activated a specific neural population without surgical intervention.

Chalasani says that one of the big goals in neuroscience is to "understand how the brain decodes changes in the environment and generates behaviors." He adds, "In order to understand this, we need to figure out all of the cells involved, their connections, and also an ability to manipulate them. Without this ability to manipulate we would not have a complete understanding.”

Previously Chalasani has been studying the neurology of nematodes in his research on fear and anxiety because of its incredibly simple brain. “The nematode has just 302 neurons,” he says. “We know all of them and their connections, and that if you manipulate neuron 1, you’ll get a certain behavior."

The more complex the animal, the more neurons you’ll find—mice have approximately 75 million neurons, and humans have more than 86 billion—which makes isolating specific neurons more difficult. Next they plan to work with mice brains.

While this research might seem esoteric to the layperson, Chalasani says these ultrasound-activated proteins are a “new tool set” to understand the neurological underpinnings of human behavior. "We want to understand the basic biology to come up with better drugs and treatments," he says. "Perhaps that will be translatable to humans as well. Anxiety and aging are huge problems we need to address, and the science requires building new technology. That’s how sonogenetics came to be."

Sonogenetics evolved from an existing method of activating brain cells called optogenetics in which a fiber optic cable is inserted into the brain of an animal, most often a mouse, and light is shined directly on the neurons. Those neurons with potassium ion channels will become activated. “In this approach, when light of a particular wavelength hits the protein, it becomes active and opens up, and allows ions of a certain charge to get into the cell,” says Chalasani.

The problem with optogenetics is that most animals have extremely dense skin. To get the light into the cells, a neurosurgeon must drill a small hole into the head and skull, and insert an optic fiber cable. In humans, procedures of these sorts are not optimal, to say the least.

Sonogenetics, on the other hand, is noninvasive. “We wanted to come up with a way that would work for other animals and use a trigger where you didn’t need any surgery,” says Chalasani. “Medical sonograms have been used safely for years to image the brain in humans. It’s a safe method,” he says. He laughingly adds that some people have asked him if this is the first step in science fiction–style mind control, but he assures them it’s not.

He hopes that some day this research can be used, for instance, to treat Parkinson’s disease, or to target the insulin-producing cells in the pancreas. Currently there’s a method of treatment in which an electrode can be surgically implanted into the brain of a Parkinson’s sufferer, which reduces symptoms dramatically. “As you can imagine, it’s an incredibly dangerous operation, and the neurosurgeon must be extremely precise,” he says.

Patients have months of recuperation, and surgeons require extensive training. “Our hope for the future would be if we found a way to deliver TRP-4 or some other ultrasound sensitive protein to that part of the brain precisely," Chalasani says. "Then you wouldn’t need any surgery.”

Sonogenetics opens the door to these new possibilities. “We have a new set of proteins that you can use, say if you are studying the heart, or cancer cells, or insulin production," he says. "We are a community of scientists, after all. If we get results we share them, so everybody can use them.”