Ultrasound neuromodulation through nanobubble-actuated sonogenetics

Ultrasound neuromodulation is a promising new method to manipulate brain activity noninvasively. Here, we detail a neurostimulation scheme using gas-filled nanostructures, gas vesicles (GVs), as actuators for improving the efficacy and precision of ultrasound stimuli. Sonicated primary neurons displayed dose-dependent, repeatable Ca2+ responses, closely synced to stimuli, and increased nuclear expression of the activation marker c-Fos only in the presence of GVs but not without. We identified mechanosensitive ion channels as important mediators of this effect, and neurons heterologously expressing the mechanosensitive MscL-G22S channel showed greater activation at lower acoustic pressure. This treatment scheme was also found not to induce significant cytotoxicity, apoptosis or membrane poration in treated cells. Altogether, we demonstrate a simple and effective method to achieve enhanced and more selective ultrasound neurostimulation. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY