The Noninvasive Sonothermogenetics Used for Neuromodulation in M1 Region of Mice Brain by Overexpression of TRPV1.

Abstract

Sonogenetics is preferred for neuroregulation and the treatment of brain diseases due to its noninvasive properties. Ultrasonic stimulation produces thermal and mechanical effects, among others. Since transient receptor potential vanilloid 1 (TRPV1) could be activated at 42°C, it is overexpressed in the M1 region of the mouse motor cortex to sense the change of temperature upon being stimulated by focused ultrasound. Whether the heat generated by ultrasonic stimulation could activate TRPV1 in the M1 region and induce changes in electromyography (EMG) signals collected from the mice's triceps was carefully verified. The position of the focused ultrasound and the temperature of the tissue at the location of the focused position were simulated using COMSOL software and verified via experiments. For Neuro-2a cells with TRPV1 overexpression, 42°C could activate the TRPV1 and induce calcium influx. For mice with TRPV1 overexpression in the M1 region, tissue temperature of >42°C in the M1 region induces an increased number of cfos, suggesting that neurons with overexpressed TRPV1 in the M1 region can be activated using focused ultrasound. Furthermore, when the temperature is >42°C, the peak-to-peak value of the EMG signal for mice with TRPV1 overexpression in the M1 region was higher than that for mice without TRPV1 overexpression. The immunohistochemical results showed that ultrasound was not harmful to the stimulation site. The noninvasive ultrasound stimulation combined with thermosensitive protein TRPV1 overexpressed in neurocytes as sonothermogenetics technology has great potential to be used for the treatment of neurological diseases.