Neurological disorders such as Parkinson’s disease and epilepsy have had some success in treatment with deep brain stimulation, but these require the implantation of a surgical device.
A multidisciplinary team from the University of Washington in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn on and off specific types of neurons in the brain and precisely control activity. motor without implantation of a surgical device.
The team, led by Hong Chen, assistant professor of biomedical engineering at the McKelvey School of Engineering and radiation oncology at the School of Medicine, is the first to provide direct evidence showing non-invasive and type-specific activation of neuron cell in the brain. by combining the heating effect induced by ultrasound and genetics, which they named sonothermogenetics.
It is also the first work to show that the combination of ultrasound and genetics 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 National Institutes of Health’s BRAIN initiative, have been published online at Brain stimulation May 11, 2021.
The senior research team included renowned experts in their fields from the McKelvey School of Engineering and the School of Medicine, including Jianmin Cui, professor of biomedical engineering; Joseph P. Culver, professor of radiology, physics and biomedical engineering; Mark J. Miller, associate professor of medicine in the Division of Infectious Diseases 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 free-moving mice while targeting a deep brain site. Sonothermogenetics has the potential to transform our research approaches in neuroscience and to discover new methods for understanding and treating disorders of the human brain. “
Hong Chen, Assistant Professor, Biomedical Engineering, McKelvey School of Engineering
Using a mouse model, Chen and the team delivered a viral construct containing TRPV1 ion channels to genetically selected neurons. Then, they delivered a small blast of heat via low-intensity focused ultrasound to selected neurons in the brain via 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 worn on the head of free-moving mice to target different locations throughout the brain,” said Yaoheng Yang, the paper’s first author and graduate student in biomedical engineering. “Because it is not invasive, this technique has the potential to be extended to large animals and potentially to humans in the future.”
The work builds on research from Cui’s lab that was published in Scientific Reports in 2016. Cui and his team discovered for the first time that ultrasound alone can influence ion channel activity and could lead to new, non-invasive ways to control the activity of specific cells.
In their work, they found that focused ultrasound modulated the currents flowing through ion channels on average by up to 23%, depending on the channel and the intensity of the stimulus. As a result of this work, the researchers found nearly 10 ion channels with this ability, but all of them are mechanosensitive and not thermosensitive.
The work also draws on the concept of optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep within the brain. While optogenetics has increased the discovery of new neural circuits, its depth of penetration is limited due to light scattering and requires surgical implantation of optical fibers.
Sonothermogenetics has the promise of targeting any location in the mouse brain with millimeter resolution without causing brain damage, Chen said. She and the team continue to optimize the technique and further validate their results.