A new tool activates deep brain neurons by combining ultrasound and genetics


Credit: University of Washington at St. Louis

Neurological disorders such as Parkinson’s disease and epilepsy have had some treatment success with deep brain stimulation, but require the implantation of a surgical device. A multidisciplinary team from the University of Washington at St. Louis has developed a new brain stimulation technique using a focused ultrasound that is able to turn specific types of neurons in the brain on and off and accurately control motor activity without the implantation of surgical devices.

The team, led by Hong Chen, assistant professor of biomedical engineering at the McKelvey School of Engineering and Radiation Oncology in the School of Medicine, is the first to provide direct evidence showing noninvasive activation and specific to the cell type of neurons in the brain. of mammals combining the effect of ultrasound-induced heating and genetics, which they have called sonothermogenetics. It is also the first work to show that ultrasound-genetic combination can robustly control behavior by stimulating a specific target deep in the brain.

The results of the three years of research, funded in part by the BRAIN initiative of the National Institutes of Health, were published online at Brain stimulation May 11, 2021.

The senior research team included renowned experts in their fields from both the McKelvey School of Engineering and the Faculty of Medicine, including Jianmin Cui, a professor of biomedical engineering; Joseph P. Culver, professor of radiology, physics, and biomedical engineering; Mark J. Miller, associate professor of medicine in the Infectious Diseases Division of the Department of Medicine; and Michael Bruchas, formerly of the University of Washington, now professor of anesthesiology and pharmacology at the University of Washington.

“Our work provided evidence that sonothermogenetics evokes behavioral responses in freely moving mice as they target a deep site in the brain,” Chen said. “Sonothermogenetics has the potential to transform our approaches to neuroscience research and discover new methods for understanding and treating human brain disorders.”

Using a file , Chen, and the team delivered a viral construct containing TRPV1 ion channels to genetically selected neurons. They then delivered a small burst of heat using a low-intensity focused ultrasound to selected neurons in the brain using a portable device. The heat, only a few degrees warmer than body temperature, activated the TRPV1 ion channel, which acted as a switch to turn neurons on or off.

“We can move the ultrasound device that is carried in the head of free-moving mice to go to different locations around the brain,” said Yaoheng Yang, first author of the paper and a graduate student in biomedical engineering. “Because it is non-invasive, this technique has the potential to be scaled up to large, potentially human animals in the future.”

The work is based on research conducted in the Cui laboratory that was published in Scientific reports in 2016. Cui and his team first found that ultrasound alone can influence ion channel activity and can lead to new, non-invasive ways to monitor specific cell activity. In their work, they found that focused ultrasound modulated the currents flowing through the ion channels averaging up to 23%, depending on the channel and the intensity of the stimulus. After this work, the researchers found about 10 ion channels with this ability, but they are all mechanosensitive, not thermosensitive.

The work also builds on the concept of optogenetics, the combination of directed expression of light-sensitive ion channels, and the precise delivery of light to stimulate deep neurons in the brain. Although optogenetics has increased the discovery of new neural circuits, penetration depth is limited due to light scattering and requires surgical implantation of optical fibers.

Sonothermogenetics promises to target any location in the mouse brain with a resolution at the millimeter scale without causing damage to the , Said Chen. She and the team continue to optimize the technique and further validate their findings.

Focused ultrasound allows accurate non-invasive therapy

More information:
Yaoheng Yang et al, Sonothermogenetics for non-invasive, cell-specific deep brain neuromodulation, Brain stimulation (2021). DOI: 10.1016 / j.brs.2021.04.021

Citation: A new tool activates deep brain neurons combining ultrasound and genetics (2021, May 28) retrieved May 29, 2021 at https://medicalxpress.com/news/2021-05-tool-deep-brain-neurons- combining.html

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