Though a neuron’s cell body is small, its projections may extend across the entire brain, branching tens to hundreds of times and intertwining with other neurons’ projections along the way. Due to their complex three-dimensional morphology, neuronal structures are hard to profile with traditional section-based histology (where, for example, transverse axons appear as small dots). Along the same lines, brain protein distributions and functions are likely not to be refined to the original cell body regions, but exhibit rather complex three-dimensional patterns and attributes.

Imaging the intact brain in three-dimensions provides a more accurate and complete characterization of the structures which compose the brain’s functional circuitry. Through this method, we can also more effectively assess changes in proteomic distribution that occur across the brain due to genetic disorders or disease.

While our interest and focus are on the nervous system, our protocols and resources could be adapted to other tissues and organs across broad animal species to appreciate organ/system level molecular patterns and cellular interactions.