Analysis of Subcortical Human Brain Structure Using Cellular Resolution Cytoarchitectonic and Chemospecific Maps

COEX 

The cellular anatomy of the human basal ganglia, thalamus and brainstem is generally presented as 2D images in print or digitized formats. 3D reconstruction of brain histology is generally difficult due to a lack of serial sections and technical challenges in reformatting stained 2D slices. Volumetric reconstruction, visualization and annotation of cytoarchitecture can also be challenging in human brain due to large size and high section numbers, which requires intensive computer processing power for 3D visualization and analysis. Unique datasets like the BigBrain allow visualization of the human brain histology at cellular resolution, and advanced software tools allow 3D navigation in any plane and annotation. We will review our recent work that takes advantage of cellular resolution 3-D datasets to annotate nuclei and neighboring tracts of the human basal ganglia, thalamus and brainstem.

Beyond cytoarchitecture, the mammalian brain is characterized by a rich and diverse chemoarchitectural content that defines structure and allows normal function. Compared to non-primate mammals, there is a dearth of detailed knowledge of the chemical anatomy of the primate subcortical brain especially in 3-D format. By way of example, we will present our recent work on creation of a chemo-specific 3D map of the subcortical human brain based on over 2000 serial sections stained with immunochemical markers. We will focus on digital reconstruction and annotation of the dopaminergic system of the brainstem and basal forebrain. To increase utility in brain imaging research these histological and histochemical atlases can be registered to standardized MRI spaces (e.g., The MNI stereotaxic space). As practical clinical applications, these novel atlases can also be used to: a) analyze the MRI location of electrodes in patients who had deep brain stimulation surgery, and b) compare mDA cell types and pathways in healthy brain with similar chemospecific datasets from patients with Parkinson’s disease.