- Researchers conducted a preclinical study to determine the potential role of genetics in brain neuromodulation.
- They found that the mechanosensitive ion channel gene, Piezo1, mediated ultrasound neuromodulation.
- The protein encoded by Piezo1 is a mechanically activated ion channel that links mechanical forces to biological signal
The research groups of Zhihai Qiu, PhD, from the Guangdong Institute of Intelligent Science and Technology in Guangdong, China, and Lei Sun, PhD, from Hong Kong Polytechnic University, recently completed a study to better understand the mechanism behind ultrasound stimulation of the brain. The team evaluated behavior, direct neuron’s response, and molecular testing to determine the role of the Piezo1 gene. The protein encoded by Piezo1 is a mechanically activated ion channel that links mechanical forces to biological signals.
These teams found that neuronal response to low-intensity transcranial ultrasound stimulation* was significantly reduced after knocking out Piezo1. Neurons with endogenous Piezo1 expression, however, had an increased neuronal response. Knocking out Piezo1 in the right motor cortex of mice significantly reduced calcium responses, limb movement, and muscle electromyogram responses. Brain areas that had higher Piezo1 expression (such as the central amygdala) were more sensitive to ultrasound stimulation than areas with lower expression (such as the cortex).
“This study fulfills the mechanism gap for in vivo ultrasound neuromodulation,” said Dr. Sun. “It has great potential for translation into the clinic.”
Beyond discovering Piezo1’s role in ultrasound modulation of neurons, the researchers proved that the role of astrocytic Piezo1 is limited, indicating a direct neuromodulation effect of ultrasound. Although previous studies showed that auditory confound may contribute to the ultrasound effect in vivo, this effect did not confound in this study. Moreover, the researchers applied a smoothed ultrasound wave and randomized ultrasound stimulation (i.e., the ultrasound amplitude and interval times were not applied in an order) in one of the behavioral studies and found a consistent effect, demonstrating that Piezo1 mediated the ultrasound neuromodulation in vivo.
“Smooth ultrasound wave and randomized ultrasound stimulation application is an objective way of studying ultrasound neuromodulation,” said Dr. Sun. “I believe this method should be adopted in further research. Another interesting finding was that Piezo1 was electively expressed in some emotional brain areas. Therefore, ultrasound neuromodulation may be applied in psychiatric disease investigation and even treatment.”
*Ultrasound equipment and parameters: A 0.5-MHz lithium niobate ultrasound transducer applied 0.35/0.45-MPa ultrasound stimuli with 500-µs tone burst, 1-kHz pulse repetition frequency, 50/250/500-ms duration, and 5-second intervals. The experimenter performing the ultrasound stimulation was blinded to which group the animal belonged.
Investigator Profile: Lei Sun, PhD September 2022
A Cell-Specific Focused Ultrasound Neuromodulation Technique September 2020