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.Apply for RFA MH 23 295
- 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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Frequently Asked Questions (FAQs) - NIH BRAIN Initiative RFA-MH-23-295
What is RFA-MH-23-295 focused on?
RFA-MH-23-295 supports the development and validation of new neurotechnology tools designed specifically to study and influence cell-specific and circuit-specific activity in the brains of humans and non-human primates. The intent is to move beyond tools optimized for small animal models and advance technologies that work reliably in large, complex brains that are more directly relevant to human biology and potential clinical use.
What is the bigger problem this funding opportunity is trying to solve?
The opportunity targets a major gap in neuroscience and medicine: many brain disorders are fundamentally problems of malfunctioning neural circuits, but current methods often cannot monitor those circuits with enough specificity or intervene in a way that is both safe and minimally invasive. By enabling more precise measurement, mapping, or manipulation of defined cell types and/or defined circuits in large brains, these tools are meant to remove key bottlenecks that slow progress toward transformative treatments.
Which species or systems are the main priority for tool development?
The emphasis is on tools that work in human and non-human primate brains. The announcement highlights that many existing advanced tools were built and tested primarily in rodents, fish, and flies, and this program prioritizes adapting or reinventing technologies so they function in large brains.
Why does NIH emphasize tools for large, complex brains instead of rodents?
Large brains introduce challenges that do not show up the same way in small animal models, including scale, access, heterogeneity, immune response, delivery constraints, and differences in circuit architecture. This funding opportunity focuses on addressing these barriers directly so that cell- and circuit-specific strategies can be used reliably in primate and human-relevant contexts.
What types of tools or capabilities are encouraged under this opportunity?
The opportunity emphasizes tool development that helps researchers precisely measure, map, or manipulate defined cell types and/or defined circuits in large brains. Practical examples of encouraged capabilities include methods that improve targeted delivery, increase specificity of expression or engagement, and enable clearer readouts of circuit function at the relevant spatial and temporal scales.
Does this funding opportunity relate to gene-therapy-like or viral delivery approaches?
Yes. The announcement highlights that gene-therapy-like strategies and viral delivery of genetic constructs are increasingly viewed not only as research tools but also as potential therapeutic approaches. Because of that, the program places added importance on solving real-world barriers to delivery and specificity in large brains.
Is this a new announcement or an update to a previous one?
This funding opportunity is a reissue of an earlier announcement (RFA-MH-22-115). It was updated to comply with NIH Data Management and Sharing Policy requirements.
What award mechanism is used (and what does it imply for project structure)?
The award uses a UG3/UH3 phased cooperative agreement structure. This typically supports a milestone-driven approach with an initial development and feasibility phase (UG3) followed by an implementation/expansion phase (UH3) if predefined goals are met. Because it is a cooperative agreement, NIH program staff are likely to have substantial involvement through milestones and coordination.
What does "Clinical Trial Optional" mean for applicants?
"Clinical Trial Optional" means applicants may propose studies that include clinical trials if appropriate, but they are not required to include a clinical trial. The program is focused on tool development and validation in relevant large-brain settings, regardless of whether a clinical trial is part of the project.
How important is validation in this program?
Validation is central. The opportunity emphasizes that it is not enough to propose a promising tool concept. Successful applications are expected to include clear and rigorous plans to demonstrate that the tool works as intended in relevant large-brain settings and that it meaningfully enables the intended measurements or interventions.
What kind of outcomes is NIH looking for from supported projects?
The intended outcomes include next-generation tools that can probe and control neural activity with cell-type and circuit-level precision in humans and non-human primates. The broader impact is to remove practical barriers to targeted delivery and specificity, strengthen the experimental foundation for understanding how circuits produce brain function, and accelerate the path toward safer, more precise future interventions for brain disorders.
Who is eligible to apply?
Eligibility is broad. Eligible applicants include 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 (501(c)(3) and non-501(c)(3)); for-profit organizations (including those other than small businesses); and small businesses.
Are minority-serving institutions and community-based organizations eligible?
Yes. The announcement explicitly notes additional eligible applicants such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, AANAPISI institutions, and faith-based or community-based organizations.
Can federal agencies, U.S. territories, or foreign entities apply?
Yes. The eligibility list includes eligible federal agencies, U.S. territories or possessions, and non-U.S. (foreign) entities and regional organizations.
Which agency is offering this opportunity?
This opportunity is offered by the National Institutes of Health (NIH) as a discretionary cooperative agreement and is part of the NIH BRAIN Initiative.
Are there specific program identifiers associated with this funding opportunity?
Yes. The opportunity 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. This reflects the cross-institute nature of BRAIN-related activities.
What are the key dates mentioned in the public summary?
The posting lists a creation date of May 8, 2023, and an original closing date of June 7, 2024.
Is there an award ceiling or an expected number of awards listed?
The public summary provided does not state an award ceiling or the expected number of awards.
What does NIH mean by "cell-specific" and "circuit-specific" in this context?
Within the scope of this opportunity, "cell-specific" and "circuit-specific" refer to the ability to precisely measure, map, or manipulate defined cell types and/or defined neural circuits in large brains. The goal is to achieve specificity that is high enough to support meaningful scientific conclusions and, longer term, enable more precise intervention strategies.
What kinds of barriers are projects expected to address?
Projects are expected to directly address barriers that limit translation of tools from small animals to primates and humans. The announcement calls out challenges such as scale, access, heterogeneity, immune response, delivery constraints, and circuit architecture, particularly where these issues block eventual clinical intervention using cell- and circuit-specific approaches.
How does the phased UG3/UH3 approach relate to milestones?
The UG3/UH3 structure is typically milestone-driven. A project begins with a development and feasibility phase (UG3). Transition to the implementation/expansion phase (UH3) is expected to depend on meeting predefined goals, reflecting the program's emphasis on measurable progress and coordinated oversight common to cooperative agreements.
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| BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed) Apply for RFA EY 23 001 Funding Number: RFA EY 23 001 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $400,000 |
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| BRAIN Initiative Connectivity across Scales Data Coordinating Center (BRAIN CONNECTS DCC) (U24 Clinical Trial Not Allowed) Apply for RFA NS 24 028 Funding Number: RFA NS 24 028 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
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