Region-specific effects of ultrasound on individual neurons in the awake mammalian brain

Ultrasound modulates brain activity. However, it remains unclear how ultrasound affects individual neurons in the brain, where neural circuit architecture is intact and different brain regions exhibit distinct tissue properties. Using a high-resolution calcium imaging technique, we characterized the effect of ultrasound stimulation on thousands of individual neurons in the hippocampus and the motor cortex of awake mice. We found that brief 100-ms-long ultrasound pulses increase intracellular calcium in a large fraction of individual neurons in both brain regions. Ultrasound-evoked calcium response in hippocampal neurons exhibits a rapid onset with a latency shorter than 50 ms. The evoked response in the hippocampus is shorter in duration and smaller in magnitude than that in the motor cortex. These results demonstrate that noninvasive ultrasound stimulation transiently increases intracellular calcium in individual neurons in awake mice, and the evoked response profiles are brain region specific.