%0 journal article %@ 2041-1723 %A Bosch, C.,Ackels, T.,Pacureanu, A.,Zhang, Y.,Peddie, C.J.,Berning, M.,Rzepka, N.,Zdora, M.-C.,Whiteley, I.,Storm, M.,Bonnin, A.,Rau, C.,Margrie, T.,Collinson, L.,Schaefer, A.T. %D 2022 %J Nature Communications %N 1 %P 2923 %R doi:10.1038/s41467-022-30199-6 %T Functional and multiscale 3D structural investigation of brain tissue through correlative in vivo physiology, synchrotron microtomography and volume electron microscopy %U https://doi.org/10.1038/s41467-022-30199-6 1 %X Understanding the function of biological tissues requires a coordinated study of physiology and structure, exploring volumes that contain complete functional units at a detail that resolves the relevant features. Here, we introduce an approach to address this challenge: Mouse brain tissue sections containing a region where function was recorded using in vivo 2-photon calcium imaging were stained, dehydrated, resin-embedded and imaged with synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT). SXRT provided context at subcellular detail, and could be followed by targeted acquisition of multiple volumes using serial block-face electron microscopy (SBEM). In the olfactory bulb, combining SXRT and SBEM enabled disambiguation of in vivo-assigned regions of interest. In the hippocampus, we found that superficial pyramidal neurons in CA1a displayed a larger density of spine apparati than deeper ones. Altogether, this approach can enable a functional and structural investigation of subcellular features in the context of cells and tissues.