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Significance  Since the invention of optogenetics, using light to control the activity of individual neurons and dissect the complex neural circuits has been a powerful tool for neuroscience owing to the high temporal precision and neuron-type specificity. However, one of the major challenges of optogenetics is the invasive delivery of light sources such as fiber optics inside the brain of live animals due to limited tissue penetration of photons. Here, we report a method termed “sono-optogenetics,” which provides minimally invasive optogenetic neuromodulation in the brain without any scalp incision, craniotomy, or brain implant. Sono-optogenetics delivers nanoscopic light sources via the endogenous blood circulation and provides millisecond-timescale switching of light emission for optogenetic neuromodulation via brain-penetrant focused ultrasound.

Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics