Ultrasonic local anesthetic uncaging enables noninvasive, targeted, and transient knock-out of brain function

Noninvasive, spatially localized brain inhibition would enable precise neural circuit interrogation, mapping, and treatment. We previously presented SonoRopi, an acoustically activatable liposomal formulation of ropivacaine, and demonstrated its utility for targeted peripheral nerve anesthesia. Here, we extend SonoRopi to localized brain anesthesia following intravenous administration and transcranial focused ultrasound application. Ultrasonic uncaging of SonoRopi releases ropivacaine, which crosses the intact blood-brain barrier to anesthetize the sonicated region. SonoRopi uncaging in mouse primary visual cortex suppressed visually evoked cortical activity for one hour, while uncaging in rat somatosensory hindlimb cortex produced lateralized, reversible hindlimb sensory anesthesia. Off-target control sonication preserved function in both paradigms. No acute histologic injury or open-field behavioral abnormalities were detected following this intervention. SonoRopi thereby enables noninvasive, spatially targeted, reversible brain inhibition with physiologic and behavioral efficacy in two rodent species.