Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)
Abstract Optical control of neural ensemble activity has been crucial for understanding brain function and disease, yet no technology can achieve optogenetic control of very large numbers of neurons at extremely fast rates over a large volume. State-of-the-art multiphoton holographic optogenetics requires high power illumination that only address relatively small populations of neurons in parallel. Conversely, one-photon holographic techniques can stimulate more neurons but with a trade-off between resolution and addressable volume. We introduce a new one-photon light sculpting technique, termed Three-Dimensional Multi-site random Access Photostimulation (3D-MAP), that simultaneously overcomes all these limitations by dynamically modulating light in both the spatial and angular domain at multi-kHz rates. Electrophysiological measurements confirm that 3D-MAP achieves high spatial precision in vitro and in vivo. Using 3D-MAP, we then interrogate neural circuits with 3D multi-site illumination with high resolution over a large volume of intact brain that existing techniques cannot achieve.