Advances in computer-generated holography for targeted neuronal modulation

Genetically encoded calcium indicators and optogenetics have revolutionized neuroscience by enabling the detection and modulation of neural activity with single-cell precision using light. To fully leverage the immense potential of these techniques, advanced optical instruments that can place a light on custom ensembles of neurons with a high level of spatial and temporal precision are required. Modern light sculpting techniques that have the capacity to shape a beam of light are preferred because they can precisely target multiple neurons simultaneously and modulate the activity of large ensembles of individual neurons at rates that match natural neuronal dynamics. The most versatile approach, computer-generated holography (CGH), relies on a computer-controlled light modulator placed in the path of a coherent laser beam to synthesize custom three-dimensional (3D) illumination patterns and illuminate neural ensembles on demand. Here, we review recent progress in the development and implementation of fast and spatiotemporally precise CGH techniques that sculpt light in 3D to optically interrogate neural circuit functions.