NIH BRAIN Initiative Connectivity across Scales (CONNECTS): The Past, Present, and Future of Brain-wide Connectivity Mapping

The NIH BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS) program is a coordinated effort aimed at developing the research capacity and technical capabilities to generate wiring diagrams that can span entire brains across multiple scales. A central goal of BRAIN CONNECTS is to enable generation of comprehensive wiring diagrams that allow scientists to identify conserved wiring principles, test new hypotheses about how brain circuits process information and produce behavior, and develop new approaches for precise diagnosis and targeted therapies for neurological and psychiatric disorders. This talk will address current challenges to brain-wide connectivity mapping and highlight recent milestones towards producing large scale reconstructions of synaptic connectivity in Drosophila, mouse, and human brains. We will provide an overview of technology development that is currently supported through the BRAIN CONNECTS program, including electron microscopy and optical techniques for comprehensive nanoscale reconstruction of neurons and their synapses, nucleotide barcoding techniques that allow dense mapping of single neuron projection patterns across species, and multimodal imaging of primate brains to map long-range axonal projections at high resolution. We will also describe integrated efforts to build pipelines, models, and infrastructure for scalable data processing, analysis, integration across modalities, and dissemination. 

Learning Objectives:

1. Identify recent advances that demonstrate feasibility of generating brain-wide wiring diagrams.

2. Describe current challenges to scaling connectivity mapping to full brains. 

3. Compare approaches to connectivity mapping at various scales.