Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.29.124727v1?rss=1 Authors: Qin, Z., Chen, C., He, S., Wang, Y., Tam, K. F., Ip, N. Y., Qu, J. Y. Abstract: Optical deep brain imaging in vivo at high resolution has remained a great challenge over the decades. Two-photon endomicroscopy provides a minimally invasive approach to image buried brain structures, once it is integrated with a gradient refractive index (GRIN) lens embedded in the brain. However, its imaging resolution and field of view are compromised by the intrinsic aberrations of the GRIN lens. Here, we advance two-photon endomicroscopy by adding adaptive optics(AO) based on the direct wavefront sensing of the descanned fluorescent guide star created by two-photon excitation, which enables effective correction of the aberrations and recovery of diffraction-limited resolution over a much extended imaging volume (300 m on each side). Benefiting from a precompensation strategy based on a lookup table, we achieved in vivo structural imaging of pyramidal neurons at synaptic resolution across all layers of the mouse hippocampus CA1. Moreover, by combining the AO endomicroscope system with a rapid multiplane imaging technique, we demonstrated simultaneous calcium imaging of hippocampal neuronal somata and dendrites in awake behaving mice. Our study holds great promise to facilitate brain research by enabling large-volume deep brain imaging in vivo at high resolution. Copy rights belong to original authors. Visit the link for more info