A Wearable Focused Ultrasound Device for Sonogenetics in Freely Moving Mice

Sonogenetics, which utilizes ultrasound to modulate the activity of neurons expressing ultrasound-sensitive actuators, has emerged as a promising approach for implant-free, cell-type-specific neuromodulation. However, wearable transcranial focused ultrasound (tFUS) devices are needed to enable sonogenetic neuromodulation in freely moving mice, thereby facilitating the study of naturalistic behavioral responses with minimal physical constraints. To address this need, we present a fully validated protocol for the design, fabrication, and characterization of a wearable tFUS device. Our protocol details the selection of piezoelectric material, transducer fabrication and calibration, and installation of the device on the mouse head. We also provide a detailed protocol for using this tFUS device for performing sonogenetics in freely moving mice. The device's efficacy in sonogenetic neuromodulation has been demonstrated in our previously published studies. The device can be used in a broad range of applications, including ultrasound neuromodulation (without genetics). All design files and accompanying software are freely available as open-source resources. This protocol is intended to lower the barrier to entry and facilitate the broader adoption of tFUS techniques in neuroscience research.