Correlative microscopy: A powerful tool for exploring neurological cells and tissues

Imaging tools for exploring the neurological samples have seen a rapid transformation over the last decade. Approaches that allow clear and specific delineation of targeted tissues, individual neurons, and their cell–cell connections as well as subcellular constituents have been especially valuable. Considering the significant complexity and extent to which the nervous system interacts with every organ system in the body, one non-trivial challenge has been how to identify and target specific structures and pathologies by microscopy. To this end, correlative methods enable one to view the same exact structure of interest utilizing the capabilities of typically separate, but powerful, microscopy platforms. As such, correlative microscopy is well-positioned to address the three critical problems of identification, scale, and resolution inherent to neurological systems. Furthermore, the application of multiple imaging platforms to the study of singular biological events enables more detailed investigations of structure–function relationships to be conducted, greatly facilitating our understanding of relevant phenomenon. This comprehensive review provides an overview of methods for correlative microscopy, including histochemistry, transgenic markers, immunocytochemistry, photo-oxidation as well as various probes and tracers. An emphasis is placed on correlative light and electron microscopic strategies used to facilitate relocation of neurological structures. Correlative microscopy is an invaluable tool for neurological research, and we fully anticipate developments in automation of the process, and the increasing availability of genomic and transgenic tools will facilitate the adoption of correlative microscopy as the method of choice for many imaging experiments.

► We review correlative microscopy methods used for neurobiology.
► Classical techniques use histochemistry, immunocytochemistry, and neural tracers.
► Contemporary approaches include photo-oxidation, array tomography, and genomic approaches.
► Correlative microscopy is needed to target specific structures for electron microscopy.