Circuit Diagrams

ABSTRACT Morphology is an essential phenotype in the characterization of cells and their states. It reflects the progression of functional cellular processes, such as morphogenesis, migration, or dendrite arborization, and can be indicative of disease. Delineating the molecular pathways that underlie morphological phenotypes is critical to understanding the relation between genetic pathways, morphology, and function of cells in the brain.

The brain is a massively interconnected network of specialized circuits. Understanding how these circuits support sensation, perception, cognition, and action requires measuring activity patterns within and across regions, but the measurements themselves do not produce insight into the structure or function of the underlying neuronal system. Insight requires the applications of quantitative methods that relate neuronal activity patterns to experimentally measurable variables, including things like present and past sensory inputs, current location, and current or future motor outputs.

Bridging Function, Connectivity, and Transcriptomics of Mouse Cortical Neurons The versatile and powerful functional properties of the brain are reflected in the neuronal activity patterns and computations, and their evolution over time due to learning, homeostatic plasticity, and other processes.

Project Summary BRAIN Initiative Cell Census Network (BICCN) is completing a comprehensive cell census of the adult mouse brain, and BRAIN Initiative Cell Atlas Network (BICAN) will extend this work with emphasis on human and non- human primates.

Project Summary The BRAIN Initiative Cell Atlas Network (BICAN) will generate comprehensive molecular taxonomies and organizational principles of cell type diversity in the human and non-human primate extending comprehensive BICCN work in the mouse.

PROJECT SUMMARY The developing mouse brain is a foundational experimental model for investigation of the origins of cell types in the mammalian brain. Comprehensive knowledge of mouse brain development is critical for comparative studies of neurodevelopmental processes, which are key to understanding the remarkable evolutionary innovations that distinguish humans from other species. In addition, developmental information enables refining cell taxonomy in the adult brain by incorporating knowledge of cell type and lineage origins into adult cell classification.

PROJECT SUMMARY/ABSTRACT The human brain exhibits profound diversity in biological function and vulnerability to disease. Despite the biomedical and cultural importance of inter-individual variation, we know relatively little about its underlying cellular and molecular substrates. In this work we will leverage new technologies in single-cell and spatial genomics to construct an Atlas of Human Brain Cell Variation. We will analyze tens of millions of cells from more than 200 people by single-nucleus RNA-seq and single-nucleus ATAC-seq, and a subset of these by spatial transcriptomics.

PROJECT SUMMARY This project will create scalable resources that will be critical to the development of BRAIN Initiative Cell Atlas Network (BICAN) consortium brain atlases. This team will focus on the development of common molecular data processing pipelines that are cloud-native and FAIR.

Progress in treating brain disorders has been frustratingly slow, in large part due to the extraordinary complexity of the human brain and its inaccessibility to study. Remarkable advances in technologies for studying individual cells, most notably single cell genomics, have revolutionized the study of complex nervous tissues and have been used to map cellular diversity across the entire mouse brain with cell types defined by their specific patterns of gene usage and gene regulatory mechanisms.

As a part of BRAIN 2.0, the BRAIN Initiative Cell Atlas Network (BICAN) is expected to advance fundamental knowledge and enabling technology for classifying human brain cell types, understanding their organizational principles, and providing open-access digital brain cell reference atlases, emphasizing c