上海科技大学知识管理系统

Background: Low-intensity ultrasound is a noninvasive neuromodulation technique with the potential to focally manipulate deep brain activity at millimeter-scale resolution. However, there have been controversies over the direct influence of ultrasound on neurons, due to an indirect auditory activation. Besides, the capacity of ul-trasound to stimulate the cerebellum remains underestimated. Objective: To validate the direct neuromodulation effects of ultrasound on the cerebellar cortex from both cellular and behavioral levels.Methods: Two-photon calcium imaging were used to measure the neuronal responses of cerebellar granule cells (GrCs) and Purkinje cells (PCs) to ultrasound application in awake mice. And a mouse model of paroxysmal kinesigenic dyskinesia (PKD), in which direct activation of the cerebellar cortex leads to dyskinetic movements, was used to assess the ultrasound-induced behavioral responses. Results: Low-intensity ultrasound stimulus (0.1 W/cm2) evoked rapidly increased and sustained neural activity in GrCs and PCs at targeted region, while no significant changes in calcium signals were observed responding to off -target stimulus. The efficacy of ultrasonic neuromodulation relies on acoustic dose modified by ultrasonic duration and intensity. In addition, transcranial ultrasound reliably triggered dyskinesia attacks in proline-rich transmembrane protein 2 (Prrt2) mutant mice, suggesting that the intact cerebellar cortex were activated by ultrasound.Conclusion: Low-intensity ultrasound directly activates the cerebellar cortex in a dose-dependent manner, and thus serves as a promising tool for cerebellar manipulation.