Characterization of Ultrasound‐Driven Localized Neural Activity <i>In Vitro</i> Using a Piezoelectric Micromachined Ultrasound Transducer: Investigating Neuromodulatory Mechanisms in the Auditory Cortex

Ultrasound stimulation is a promising, low‐invasive technique that can activate deep brain regions with high spatial resolution; it holds potential for the treatment of various neurological disorders. However, the fundamental cellular mechanisms by which ultrasound induces neural activity remain incompletely understood. To address this issue, we developed a compact ultrasound stimulation device that was optimized for the local stimulation of individual neurons in vitro . We evaluated the ability of the device to induce neural activity through numerical simulations using a three‐dimensional model, and then validated these results through experimental measurements. We also analyzed calcium ion dynamics in the mouse auditory cortex in response to ultrasound stimulation; we identified four distinct patterns of calcium responses, including both excitatory and inhibitory activity. To explore the underlying mechanisms, we administered pharmacological agents that inhibit mechanosensitive ion channels. Collectively, our findings provide new insights into the biophysical mechanisms of ultrasound‐induced neural activation. © 2026 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.