Remote control for brain cells: scientists use ultrasound waves to activate neurons
Posted by admin on 13th August 2019

What if you didn’t need surgery to implant a pacemaker on a faulty heart? What if you could control your blood sugar levels without an injection of insulin, or mitigate the onset of a seizure without even pushing a button?

I and a team of scientists in my laboratory at the Salk Institute are tackling these challenges by developing a new technology known as sonogenetics, the ability to noninvasively control the activity of cells using sound.

From light to sound

I am a neuroscientist interested in understanding how the brain detects environmental changes and responds. Neuroscientists are always looking for ways to influence neurons in living brains so that we can analyze the outcome and understand both how that brain works and how to better treat brain disorders.

Creating these specific changes requires the development of new tools. For the last two decades the go-to tool for researchers in my field has been optogenetics, a technique in which engineered brain cells in animals are controlled with light. This process involves inserting an optic fiber deep within the animal’s brain to deliver light to the target region.

When these nerve cells are exposed to blue light, the light-sensitive protein is activated, allowing those brain cells to communicate with each other and modify the animal’s behavior. For example, animals with Parkinson’s disease can be cured of their involuntary tremors by shining light on brain cells that have been specially engineered making them light-sensitive. But the obvious drawback is that this procedure depends on surgically implanting a cable into the brain – a strategy that cannot be easily translated into people.

My goal had been to figure out how to manipulate the brain without using light.

Sound control

I discovered that ultrasound – sound waves beyond the range of human hearing, which are noninvasive and safe – is a great way to control cells. Since sound is a form of mechanical energy, I figured that if brain cells could be made mechanically sensitive, then we could modify them with ultrasound. This research led us to the discovery of the first naturally occurring protein mechanical detector that made brain cells sensitive to ultrasound.

Our technology works in two stages. First we introduce new genetic material into malfunctioning brain cells using a virus as a delivery device. This provides the instructions for these cells to make the ultrasound-responsive proteins.

The next step is emitting ultrasound pulses from a device outside the animal’s body targeting the cells with the sound-sensitive proteins. The ultrasound pulse remotely activates the cells.

Sound frequency ranges for infrasound, audible and ultrasound waves and the animals that can hear them. People are able to hear only between 20 Hz and 20,000 Hz.

Proof in worms

We were the first to show how sonogenetics can be used to activate neurons in a microscopic worm called Caenorhabditis elegans.

Using genetic techniques, we identified a naturally occurring protein called TRP-4 – which is present in some of the worm’s neurons – that was sensitive to ultrasound pressure changes. Sound pressure waves that occur in the ultrasonic range are above the normal threshold for human hearing. Some animals, including bats, whales and even moths, can communicate at these ultrasonic frequencies, but the frequencies used in our experiments go beyond what even these animals can detect.

My team and I demonstrated that neurons with the TRP-4 protein are sensitive to ultrasonic frequencies. Sound waves at these frequencies changed the worm’s behavior. We genetically altered two of the worm’s 302 neurons and added the TRP-4 gene that we knew from previous studies was involved with mechanosensation.

We showed how ultrasound pulses could make the worms change direction, as if we were using a worm remote control. These observations proved that we could use ultrasound as a tool to study brain function in living animals without inserting anything into the brain.