LAUSR

Significance Ultrasound can be focused through skull onto the deep brain, altering neural activity noninvasively. Despite its broad utility, the action of focused ultrasound on specific cell types is almost entirely unknown. Understanding cell type–specific responses to FUS would allow selection of ultrasound waveforms that engage the intended targets while limiting effects on off-target fields. We developed a system combining FUS targeting and optical recording of virally labeled deep brain cell types in freely behaving animals. We used the tool to identify a protocol for the hippocampus that selectively increases inhibitory neural activity while decreasing excitatory activity with high spatial specificity. The protocol robustly suppressed epileptiforms in a chronic epilepsy model demonstrating the tool’s potential for examining experimental FUS therapies.