How to Control Neurons in the Brain

Calendar February 22, 2022 | Posted by admin

Researchers out of San Diego’s Salk Institute have gotten mice to move their limbs by stimulating brain cells using ultrasound. When mice were engineered to have their brain cells produce a special protein, the researchers found that hitting them with ultrasound “turned on” the cells, causing small, but perceptible, movements in their limbs. The technique, called “sonogenetics,” is the latest in a line of methods that look to stimulate and alter neurons directly, without using drugs.

“We’ve spent so much time over the last few decades focusing on pharmacologic therapies,” said Colleen Hanlon, a biologist at Wake Forest not involved with the study. “This paper is another really important piece to this puzzle of developing neural circuit-based therapeutics for disease.”

 Sonogenetics is just one of the ways researchers have begun controlling neurons in the brain, turning them off or on at will. Perhaps the most well-known method is using electrical stimulation. In deep brain stimulation, researchers surgically implant electrodes into specific areas of the brain. When these electrodes fire off at the right time and with the right frequency, they can make tremors disappear, improve memory, and even treat depression.

Taking a step up on the wildness scale, scientists can also activate, or turn off, neurons using light, a technique called optogenetics. Optogenetics works by genetically engineering brain cells to produce light-sensitive proteins, which can be hit with a laser, causing the neuron to fire or not. A similar mechanism is behind sonogenetics, except the protein reacts to ultrasound. Ultrasound is appealing because of its well-understood safety profile and the fact that it is already used to target locations deep within the body. “Ultrasound is safe, noninvasive, and can be easily focused through thin bone and tissue to volumes of a few cubic millimeters,” the researchers wrote in their study, published in Nature Communications.

In optogenetics, by contrast, because skin and bone are opaque, even powerful lights will have a hard time reaching neurons deeper than the outer layer of the brain. Salk neuroscientist Sreekanth Chalasani and his colleagues pioneered sonogenetics several years ago in a tiny worm called a nematode. In the worms, they used an ultrasound-reacting protein called TRP-4. But when they put it into mammalian cells, well … nada. And thus began a six-year quest to find an ultrasound-reactive protein that works in mammals. They found it — a protein called TRPA1. The researchers first tested the protein in mouse neurons in the lab. When those cells reacted to ultrasound by producing electrical signals, they engineered it into living mice. When the TRPA1-producing mice were exposed to ultrasound, electrical signals coursed through their limbs — and a little bit of movement, too.

“It’s a very exciting contribution and an important step,” adds Caltech sonogenetics researcher Mikhail Shapiro, who was uninvolved with the work.  “This is one of the papers that’s come out over the last several years that shows that it’s a real possibility that you can use ultrasound to directly modulate the activity of specific neurons.”

Source: https://www.freethink.com/

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Could Sound Replace Pacemakers and Insulin Pumps?

Calendar February 10, 2022 | Posted by admin

Imagine a future in which crippling epileptic seizures, faltering hearts and diabetes could all be treated not with scalpels, stitches and syringes, but with sound. Though it may seem the stuff of science fiction, a new study shows that this has solid real-world potential.

Sonogenetics – the use of ultrasound to non-invasively manipulate neurons and other cells – is a nascent field of study that remains obscure amongst non-specialists, but if it proves successful it could herald a new era in medicine.

In the new study published in Nature Communications, researchers from the Salk Institute for Biological Studies in California, US, describe a significant leap forward for the field, documenting their success in engineering mammalian cells to be activated using ultrasound. The team say their method, which they used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps.

“Going wireless is the future for just about everything,” says senior author Dr Sreekanth Chalasani, an associate professor in Salk’s Molecular Neurobiology Laboratory. “We already know that ultrasound is safe, and that it can go through bone, muscle and other tissues, making it the ultimate tool for manipulating cells deep in the body.”

Chalasani is the mastermind who first established the field of sonogenetics a decade ago. He discovered that ultrasound — sound waves beyond the range of human hearing — can be harnessed to control cells. Since sound is a form of mechanical energy, he surmised that if brain cells could be made mechanically sensitive, then they could be modified with ultrasound.

In 2015 his research group provided the first successful demonstration of the theory, adding a protein to cells of a roundworm, Caenorhabditis elegans, that made them sensitive to low-frequency ultrasound and thus enabled them to be activated at the behest of researchers.

Chalasani and his colleagues set out to search for a new protein that would work in mammals. Although a few proteins were already known to be ultrasound sensitive, no existing candidates were sensitive at the clinically safe frequency of 7MHz – so this was where the team set their sights. To test whether TRPA1 protein could activate cell types of clinical interest in response to ultrasound, the team used a gene therapy approach to add the genes for human TRPA1 to a specific group of neurons in the brains of living mice. When they then administered ultrasound to the mice, only the neurons with the TRPA1 genes were activated.

Clinicians treating conditions including Parkinson’s disease and epilepsy currently use deep brain stimulation, which involves surgically implanting electrodes in the brain, to activate certain subsets of neurons. Chalasani says that sonogenetics could one day replace this approach—the next step would be developing a gene therapy delivery method that can cross the blood-brain barrier, something that is already being studied. Perhaps sooner, he says, sonogenetics could be used to activate cells in the heart, as a kind of pacemaker that requires no implantation.

Source: https://www.salk.edu/
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https://cosmosmagazine.com/

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