%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.