Effects of focused ultrasound in a “clean” mouse model of ultrasonic neuromodulation
Hongsun Guo,
Hossein Salahshoor,
Di Wu,
Sangjin Yoo,
Tomokazu Sato,
Doris Y. Tsao,
Mikhail G. Shapiro
Affiliations
Hongsun Guo
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Hossein Salahshoor
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA 91125, USA
Di Wu
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Sangjin Yoo
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Tomokazu Sato
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Doris Y. Tsao
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Pasadena, CA 91125, USA
Mikhail G. Shapiro
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, Pasadena, CA 91125, USA; Corresponding author
Summary: Recent studies on ultrasonic neuromodulation (UNM) in rodents have shown that focused ultrasound (FUS) can activate peripheral auditory pathways, leading to off-target and brain-wide excitation, which obscures the direct activation of the target area by FUS. To address this issue, we developed a new mouse model, the double transgenic Pou4f3+/DTR × Thy1-GCaMP6s, which allows for inducible deafening using diphtheria toxin and minimizes off-target effects of UNM while allowing effects on neural activity to be visualized with fluorescent calcium imaging. Using this model, we found that the auditory confounds caused by FUS can be significantly reduced or eliminated within a certain pressure range. At higher pressures, FUS can result in focal fluorescence dips at the target, elicit non-auditory sensory confounds, and damage tissue, leading to spreading depolarization. Under the acoustic conditions we tested, we did not observe direct calcium responses in the mouse cortex. Our findings provide a cleaner animal model for UNM and sonogenetics research, establish a parameter range within which off-target effects are confidently avoided, and reveal the non-auditory side effects of higher-pressure stimulation.
