Holographic Imaging and Stimulation of Neural Circuits.

A critical neuroscience challenge is the need to optically image and manipulate neural activity with high spatiotemporal resolution over large brain volumes. The last three decades have seen the development of calcium imaging to record activity from neuronal populations, as well as optochemistry and optogenetics to optically manipulate neural activity. These methods are typically implemented with wide-field or laser-scanning microscopes. While the former approach has a good temporal resolution, it generally lacks spatial resolution or specificity, particularly in scattering tissues such as the nervous system; meanwhile, the latter approach, particularly when combined with two-photon excitation, has high spatial resolution and specificity but poor temporal resolution. As a new technique, holographic microscopy combines the advantages of both approaches. By projecting a holographic pattern on the brain through a spatial light modulator, the activity of specific groups of neurons in 3D brain volumes can be imaged or stimulated with high spatiotemporal resolution. In a combination of other techniques such as fast scanning or temporal focusing, this high spatiotemporal resolution can be further improved. Holographic microscopy enables all-optical interrogating of neural activity in 3D, a critical tool to dissect the function of neural circuits.