BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed)

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS)

This announcement is a reissue of RFA-NS-22-049, from the following suite of BRAIN CONNECTS funding opportunities, to develop scalable technologies for brain-wide mapping of neural connectivity.  BRAIN CONNECTS is an anticipated 10-year program to develop the research capacity and technical capabilities to generate wiring diagrams that can span entire brains across multiple scales. The objective of the first five years is to develop these capabilities through innovation, iterative engineering, and optimization for the required throughput and capacity scale-up.

RFA-NS-22-047 UM1 Comprehensive Centers for Human and Non-Human Primate Brain

RFA-NS-22-048 UM1 Comprehensive Centers for Mouse Brain

RFA-NS-22-049 U01 Specialized Projects for Scalable Technologies

RFA-NS-24-028 U24 Data Coordinating Centers

Comprehensive Centers funded under RFA-NS-22-047 and RFA-NS-22-048 use the UM1 activity code for large-scale research activities with interdependent components.  Funded projects aim to establish full production pipelines, from sample collection through data integration, analysis, and dissemination, applied to sub-volumes that are sufficiently large to prove feasibility of whole-brain mapping, and chosen to test specific hypotheses relating circuit structure to function.  Specialized Projects (RFA-NS-22-049 and this re-issue) use the U01 activity code for cooperative agreements to develop current or emerging technologies for scalable mapping of brain connectivity. Data Coordinating Centers (RFA-NS-24-028) facilitate and organize the activities of the BRAIN CONNECTS Network.

Through these awards, the program will support:

• A portfolio of complementary approaches for data acquisition and reconstruction of brain connectivity, with metrics for comparing and choosing approaches
• Teams from a variety of disciplines including but not limited to neuroscience, engineering, computational and molecular biology, chemistry and physics, mathematics, computer and data sciences, and bioethics
• Engineering and innovation efforts aimed at scale-up to map entire brains with high throughput and precise fidelity
• Demonstration of lossless acquisition and accurate reconstruction, validated with ground truth data, across large distances required for whole-brain mapping
• Proof-of-concept datasets, representing large and unprecedented sub-volumes within the brain or spinal cord, aimed at understanding the wiring principles of specific circuits and their implications for neural function
• New approaches and toolsets for mining and integrating into the neuroscience knowledge base, including morphological, functional, and molecular data
• New infrastructure for the research community to discover cell types, circuit motifs, wiring principles and circuit elements, and to develop new computational and conceptual models based on these rich new sources of data

Objectives and Requirements for this Announcement

Applications to this announcement may address any aspect(s) of the production and analysis pipeline – from data collection, reconstruction, analysis, integration, dissemination, and interpretation of brain connectivity and associated data.  The proposed development must aim to enable faster, more precise, and more cost-effective generation and interpretation of brain-wide wiring diagrams.  Projects may develop and optimize current technologies or propose entirely new, disruptive, and potentially risky approaches. In all cases, the expectation is that technologies and approaches will be sufficiently scalable to enable brain-wide connectivity mapping in a subsequent five-year follow-on period, if not earlier.

Applications to this announcement are expected to complement existing BRAIN CONNECTS awards with distinct capabilities and competencies. Applicants are strongly encouraged to use NIH RePORTER to retrieve information on awards from each of aforementioned announcements.

The focus of the BRAIN CONNECTS Program is on human, NHP, and mouse brain.  For mouse, technologies must demonstrate feasibility of local and long-range cell-to-cell connectivity at the level of synaptic connections.  For human and NHP, technologies must demonstrate region-to-region connectivity at the level of axonal projections. Other species are permitted, if their use is well justified and the goal is to test and validate approaches that can be generalized across species.

The BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS) Network

Awards funded under this announcement will be integrated into the BRAIN CONNECTS Network for project coordination and program integration.  Throughout the funding period, all CONNECTS Network recipients will work cooperatively to further common goals and identify collaborative opportunities. The CONNECTS Network will develop and harmonize common data processing pipelines, integrate and disseminate data analytic tools and capabilities, initiate efforts towards a unified knowledge base for connectivity data from a variety of modalities, and organize and implement outreach and engagement to the wider research community and the general public.