Whole-brain dynamics of neuronal circuits enabled by sculpted light and light field microscopy

Capturing the dynamics of neuronal activity across whole nervous systems at high temporal resolution has been a long-standing dream in neuroscience. While point-scanning microscopy methods provide the necessary 3D resolution, their volume acquisition rates are limited. Wide-field microscopes on the other hand do not provide sufficient optical sectioning capability. We recently implemented two complementary fluorescence microscopy methods that allow for simultaneous whole-animal imaging of genetically encoded calcium indicator activity in C. elegans, and whole-brain readout in zebrafish larvae. While Wide-field Temporal Focusing Microscopy “sculpts” the spectral components of femtosecond laser pulses to achieve sectioning, Light Field Deconvolution Microscopy, a tomography related method, uses a microlens array to simultaneously capture spatial and angular information followed by computational reconstruction to acquire volumetric information from a single sensor exposure. Here, we discuss our recent results using both techniques for acquiring whole-brain functional imaging data at speeds up to tens of Hertz and near single cell resolution for small model organisms.