BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional) | RFA MH 23 295

Opportunity Information: Apply for RFA MH 23 295

The NIH BRAIN Initiative funding opportunity RFA-MH-23-295 supports the development and validation of new neurotechnology tools designed specifically for studying and influencing cell-specific and circuit-specific activity in the brains of humans and non-human primates. It is a reissue of an earlier announcement (RFA-MH-22-115) updated to comply with NIH Data Management and Sharing Policy requirements. The overall goal is to move beyond tools optimized for small animal models and push forward technologies that work reliably in large, complex brains that are more directly relevant to human biology and potential clinical use.

The program is centered on a major gap in neuroscience and medicine: many brain disorders are ultimately problems of malfunctioning circuits, but current approaches often cannot monitor those circuits with enough specificity or intervene in a way that is both safe and minimally invasive. Because of that limitation, progress toward transformative treatments has been slowed. This opportunity emphasizes tool development that can help researchers precisely measure, map, or manipulate defined cell types and/or defined circuits in large brains. In practical terms, that could include methods that improve targeted delivery, increase specificity of expression or engagement, or enable clearer readouts of circuit function at the relevant spatial and temporal scales. The announcement highlights that gene-therapy-like strategies and viral delivery of genetic constructs are increasingly seen not just as research tools, but as possible therapeutic approaches, which raises the stakes for solving real-world barriers to delivery and specificity.

A key theme is translation of innovation from traditional model organisms to primate and human-relevant contexts. Over the last decade, and especially since the launch of the BRAIN Initiative, neuroscience has produced a wave of sophisticated tools, but most were built and tested primarily in rodents, fish, and flies. This funding opportunity targets the pressing need to adapt or reinvent those tools so they can function in large brains, where issues like scale, access, heterogeneity, immune response, delivery constraints, and circuit architecture create challenges that do not show up the same way in smaller systems. Projects are expected to address these barriers directly, particularly those that stand in the way of eventual clinical intervention using cell- and circuit-specific strategies.

The award uses a UG3/UH3 phased cooperative agreement structure, which typically supports a milestone-driven approach: an initial development and feasibility phase (UG3) followed by an implementation/expansion phase (UH3) if predefined goals are met. The listing notes "Clinical Trial Optional," meaning applicants may propose studies that include clinical trials if appropriate, but they are not required to do so. Regardless of whether a clinical trial is involved, successful applications are expected to include clear, rigorous plans for validation. In other words, it is not enough to propose a promising tool concept; applicants should also show how they will demonstrate that the tool actually works as intended in relevant large-brain settings and that it meaningfully enables the intended kinds of measurements or interventions.

Eligibility is broad and includes many types of organizations: state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized tribal governments; tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (including those other than small businesses); and small businesses. The announcement also explicitly calls out additional eligible applicants such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, AANAPISI institutions, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and even non-U.S. (foreign) entities and regional organizations. This breadth is meant to encourage participation from a wide range of research, clinical, and technology-development ecosystems.

Administratively, this opportunity is offered by the National Institutes of Health as a discretionary cooperative agreement, and it is associated with multiple CFDA numbers (93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, 93.867), reflecting the cross-institute nature of BRAIN-related activities. The posting lists an original closing date of June 7, 2024, and a creation date of May 8, 2023. While the public summary does not provide a stated award ceiling or expected number of awards, the emphasis on cooperative agreement mechanisms signals that NIH program staff will likely have substantial involvement through milestones and coordination, which is common for complex tool-building efforts intended to create broadly enabling platforms.

In summary, this grant opportunity is aimed at teams that can create and convincingly validate next-generation tools capable of probing and controlling neural activity with cell-type and circuit-level precision in human and non-human primate brains. The intended impact is to remove practical barriers to targeted delivery and specificity, strengthen the experimental foundation for understanding how cellular interactions and circuits produce brain function, and accelerate the path toward future, safer, more precise interventions for brain disorders.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2023-05-08.
• Applicants must submit their applications by 2024-06-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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