High resolution ultrasonic neural modulation observed via in vivo two-photon calcium imaging

Neural modulation plays a major role in delineating the circuit mechanisms and serves as the cornerstone of neural interface technologies. Among the various modulation mechanisms, ultrasound enables noninvasive label-free deep access to mammalian brain tissue. To date, most if not all ultrasonic neural modulation implementations are based on [~]1 MHz carrier frequency. The long acoustic wavelength results in a spatially coarse modulation zone, often spanning over multiple function regions. The modulation of one brain region is inevitably linked with the modulation of its neighboring regions. To significantly increase the spatial resolution, we explored the application of high-frequency ultrasound. To investigate the neuronal response at cellular resolutions, we developed a dual-modality system combining in vivo two-photon calcium imaging and focused ultrasound modulation. The studies show that the [~]30 MHz ultrasound can suppress the neuronal activity in awake mice at 100-micron scale spatial resolutions, paving the way for high-resolution ultrasonic neural modulation.