Rapid brain-wide optogenetic screening with a noninvasive, dynamically programmable in vivo light source

Optogenetics, which uses light to control the activity of genetically defined neurons, allows the precise deconstruction of neural circuits with neuron-type specificity and millisecond resolution in behaving animals. Due to the limited penetration of light in the brain, one major challenge of in-vivo optogenetics is the invasive implantation of optical fibers. Moreover, the illumination volume in the brain is limited by the position of the optical fiber and cannot be easily repositioned during the experiment to screen other brain regions while the animal is performing a particular behavior. To address these challenges, we aim to develop a noninvasive method to produce on-demand and dynamically programmable light emission patterns throughout the entire brain of live mice. The emission patterns can be controlled by brain-penetrant focused ultrasound and switched with millisecond precision for rapid brain-wide optogenetic screening of different brain regions. The proposed method will result in a valuable tool for the broader neuroscience community to rapidly screen different brain regions underlying a certain behavior or pathology of interest in the same animals. Moreover, the proposed project provides a unique opportunity for us to offer outreach, mentorships, and internships to students from underrepresented and socioeconomically disadvantaged backgrounds.

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