Even though scientists have been captivated by the diversity of brain cells for well over a century, since the initial anatomical descriptions by Santiago Ramón y Cajal, it is only recently that the developments in new technologies allowed us to truly appreciate the astonishing complexity of cell types in the mammalian brain. Yet, even today, our knowledge of cell type anatomy and function is largely limited to a few brain areas, such as the sensory cortex or the hippocampus. This lack of whole-brain data has led to generalizations from one brain area to other regions with similar architecture. However, our preliminary studies applying quantitative whole brain analyses have revealed unexpected region specific differences in cell type ratios and uncovered new gender-based differences in cellular anatomy that can inform our understanding of brain development, wiring and function. We thus believe that closing the gaps in our knowledge of the cellular architecture of the brain will be a major contribution to enable a modern quantitative understanding of the brain as a system. Here we propose to establish an Anatomical Collaboratory for Systematic Atlasing of Cell-Type Distribution and Morphology in female and male brain. This Collaboratory will apply standardized, unbiased and largely automated methods developed in our laboratories to atlas the distribution and morphology of >80 molecularly defined cell classes and cell type across all regions of the female and male brain. This work will yield the most comprehensive characterization of cell type anatomy in the mammalian brain to date, establishing a structural basis for building an integrated Cell Type Brain Atlas. Specific Aim 1: Quantify and atlas the brainwide distribution of molecularly defined cell types. This work will generate a quantitative brain atlas of the distributions of molecularly defined cell classes and cell types within the Common Coordinated Framework (CCF) of the adult brain. Specific Aim 2: Quantify and atlas the brainwide morphologies of molecularly defined cell types. This work will generate a comprehensive structural brain atlas of somatodendritic cell-type morphologies across all CCF anatomical areas in the female and male brain. Specific Aim 3: Develop and deploy a neuroinformatics infrastructure: an integrated web portal for cell-type specific data, tools, and analytics. This work will disseminate the generated data via CSHL cell type-dedicated BrainArchitecture web portal and through the BRAIN Cell Data Center (BCDC). !

Narrative There is no topic in neuroscience that is not informed by a detailed knowledge of brain cell types and their connectivity. We propose to apply a platform of standardized and largely automated methods to generate a comprehensive and quantitative anatomical atlas of >80 molecularly defined cell classes and cell types in the female and male brain. This work will establish a structural basis for building an integrated Cell Type Brain Atlas. .