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The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired. Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged.

This Notice of Funding Opportunity (NOFO) encourages research on the biology of high confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular and circuit substrates of neural function. For the purposes of this NOFO, the term complex can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder. Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ, or in vitro experimental paradigms, e.g., model organisms or human cell-based assays. While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular and circuit mechanisms, these are neither required nor expected. Studies should not attempt to model disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). The R21 activity code is intended for early stage, high-risk, exploratory approaches or to establish proof-of-concept where there is little or no preliminary data. The resulting paradigms, component pathways and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification.

This Notice of Funding Opportunity (NOFO) encourages research on the biology of high-confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular, and circuit substrates of neural function. Studies may be either hypothesis-generating or hypothesis-testing in design and may utilize in vivo, in situ or in vitro experimental paradigms, including model organisms or human cell-based assays. Studies should aim to elucidate the neurobiological impact of individual or combined risk factors, such as the affected molecular and cellular components and their relationships within defined biological processes. The resulting paradigms, component pathways, and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification. This R01 activity code is for applications to further develop lines of inquiry where feasibility or proof-of-concept has been established.