Distribution of calbindin-positive neurons across areas and layers of the marmoset cerebral cortex.

The diversity of the mammalian cerebral cortex demands technical approaches to map the spatial distribution of neurons with different biochemical identities. This issue is magnified in the case of the primate cortex, characterized by a large number of areas with distinctive cytoarchitectures. To date, no full map of the distribution of cells expressing a specific protein has been reported for the cortex of any primate. Here we have charted the 3-dimensional distribution of neurons expressing the calcium-binding protein calbindin (CB+ neurons) across the entire marmoset cortex, using a combination of immunohistochemistry, automated cell identification, computerized reconstruction, and cytoarchitecture-aware registration. CB+ neurons formed a heterogeneous population, which together corresponded to 10–20% of the cortical neurons. They occurred in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+ neurons were concentrated in the supragranular and granular layers, there were clear global trends in their laminar distribution. For example, their relative density in infragranular layers increased with hierarchical level along sensorimotor processing streams, and their density in layer 4 was lower in areas involved in sensorimotor integration, action planning and motor control. These results reveal new quantitative aspects of the cytoarchitectural organization of the primate cortex, and demonstrate an approach to mapping the full distribution of neurochemically distinct cells throughout the brain which is readily applicable to most other mammalian species. Author summary: The cerebral cortex is the part of the brain which expanded the most in primate evolution. Part of this change corresponds to differentiation into a larger number of areas, each characterized by a different combination of cells that express different proteins, and the arrangement of these cells into layers. Finding ways to fully map this diversity has been a challenge. We have developed a workflow based on immunohistochemistry, automated cell identification, and computerized reconstruction which allowed us to map the full distribution of neurons expressing calbindin, a protein that is important for regulating the levels of intracellular calcium. This 3-dimensional map has revealed that cortical areas vary not only with respect to the number of cells expressing calbindin, but also to where they are located. This approach is readily adaptable to mapping the distribution of other proteins, across various species, which will allow future work towards understanding the anatomy, physiology and evolution of the cortex. [ABSTRACT FROM AUTHOR]