Large field-of-view volumetric deep brain imaging through gradient-index lenses

The rapid advance of genetically encoded fluorescent functional indicators has transformed neuroscience research. Fluorescence-based optical neural recording offers excellent sensitivity and spatiotemporal resolutions. A major limitation of optical measurement is the superficial access depth due to the random light scattering in the mammalian brain. Currently, implanting miniature gradient-index (GRIN) lenses has become the preferred method for deep brain optical imaging. However, the image quality and throughput are majorly impacted by the severe optical aberration of GRIN lenses. In this work, we present an easy-to-adopt solution to overcome these challenges and improve the image quality, volume, and throughput. Specifically, we develop a correction objective lens that corrects the aberration of a GRIN lens to enable high-throughput volumetric functional imaging with a ~ 400% larger field-of-view (FOV). We demonstrate the capabilities of in vivo large-FOV 3D volumetric calcium imaging by recording over 1000 neurons in deep brain regions through a 0.5 mm diameter GRIN lens. The simplicity and robust performance of the method promise broad applications in neuroscience research.