BRAIN CONNECTS: The Axonal Projectome EXchange (APEX)

Project Summary The brain is the most complex organ in the human body. Millions of interconnected cells communicate through an intricate network of pathways to give rise to our cognition, perception, and emotional experiences. At present we lack an accurate and complete map of the axonal projections that form the wiring of this network (the “pro- jectome”) in the primate brain. Such a map would be an invaluable resource for basic and clinical neuroscience, revolutionizing our understanding of the brain and advancing clinical applications in neurosurgery and neuro- modulation. Over the next five years, the BRAIN Initiative Connectivity Across Scales (CONNECTS) program is set to “develop research and techniques with the capacity to generate wiring diagrams that can span entire brains across multiple scales and species.” Five UM1 comprehensive centers (two in mouse, one in marmoset, and two in macaque/human) and several U01 specialized projects have been funded by CONNECTS to develop new technologies for data acquisition and analysis. We propose to establish the Axonal Projectome Exchange (APEX), a Data Coordinating Center (DCC) for the CONNECTS program, in response to RFA-NS-24-028. The APEX DCC will integrate and coordinate activities across CONNECTS data-generating UM1 and U01 projects that focus on multimodal imaging of axonal projec- tions in macaque and human. This includes two CONNECTS UM1s: the Center for Large-scale Imaging of Neu- ral Circuits (LINC) and the Center for Mesoscale Connectomics (CMC). The APEX DCC is a collaborative effort of investigators from the LINC and CMC consortia, and thus uniquely positioned to integrate data collected by these two centers and by any specialized projects funded by CONNECTS in this domain. The overarching goal of APEX is to enable a transformative shift toward petascale and eventually exascale primate axonal projectomes, laying the foundations for generating whole-brain wiring diagrams across scales in macaque and human at the end of this 5-year period. APEX will pursue two key objectives: First, it will coordinate consortium activities among CONNECTS projects that focus on multimodal imaging of axonal projections in macaque and human, and between these projects and other relevant efforts in CONNECTS, the BRAIN Initiative Cell Census Network, and BRAIN Initiative Cell Atlas Network. Second, it will integrate and harmonize analytic tools that are developed by its constituent UM1 and U01 projects to process multi-scale data from optical mi- croscopy, X-ray microscopy, and diffusion MRI. Rigorous standards and performance metrics will be established to benchmark analytic pipelines, ensure high data quality, and plan for scalability. APEX will contribute to building a unified knowledge base for brain connectivity across species and modalities. It will disseminate these re- sources to the scientific community, and it will establish a strong outreach and engagement strategy to com- municate the significance of the CONNECTS program's ambitious objectives to the general public.