The neuroanatomical architecture is considered to be the basis for understanding brain function and dysfunction. However, existing imaging tools have limitations for brainwide mapping of neural circuits at a mesoscale level. We developed a micro-optical sectioning tomography (MOST) system that can provide micrometer-scale tomography of a centimeter-sized whole mouse brain. Using MOST, we obtained a three-dimensional structural data set of a Golgi-stained whole mouse brain at the neurite level. The morphology and spatial locations of neurons and traces of neurites could be clearly distinguished. We found that neighboring Purkinje cells stick to each other.

The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 × 0.32 × 2.0 μm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei.

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