Principles and applications of sono-optogenetics.

Optogenetics has revolutionized neuroscience research through its spatiotemporally precise activation of specific neurons by illuminating light on opsin-expressing neurons. A long-standing challenge of in vivo optogenetics arises from the limited penetration depth of visible light in the neural tissue due to scattering and absorption of photons. To address this challenge, sono-optogenetics has been developed to enable spatiotemporally precise light production in a three-dimensional volume of neural tissue by leveraging the deep tissue penetration and focusing ability of ultrasound as well as circulation-delivered mechanoluminescent nanotransducers. Here, we present a comprehensive review of the sono-optogenetics method from the physical principles of ultrasound and mechanoluminescence to its emerging applications for unique neuroscience studies. We also discuss a few promising directions in which sono-optogenetics can make a lasting transformative impact on neuroscience research from the perspectives of mechanoluminescent materials, ultrasound-tissue interaction, to the unique neuroscience opportunities of "scanning optogenetics".