Serial sectioning and electron microscopy of large tissue volumes for 3D analysis and reconstruction: a case study of the calyx of Held.

Serial section electron microscopy is typically applied to investigation of small tissue volumes encompassing subcellular structures. However, in neurobiology, the need to relate subcellular structure to organization of neural circuits can require investigation of large tissue volumes at ultrastructural resolution. Analysis of ultrastructure and three-dimensional reconstruction of even one to a few cells is time consuming, and still does not generate the necessary numbers of observations to form well-grounded insights into biological principles.