BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed) | RFA NS 21 026

Opportunity Information: Apply for RFA NS 21 026

The National Institutes of Health (NIH) is soliciting R01 grant applications under the BRAIN Initiative for proof-of-concept testing and development of brand-new technologies and unconventional approaches that can record and modulate activity in the central nervous system (CNS). The opportunity, titled "BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-NS-21-026), is a reissue of an earlier announcement (RFA-NS-18-020) and is aimed squarely at advancing the technical foundation of modern neuroscience rather than running clinical trials in humans.

The core purpose is to make it possible to measure and manipulate brain circuit activity in ways that are currently difficult or impossible, with an emphasis on capturing dynamic signaling in the brain. Projects are expected to push toward recording and modulation at or near cellular resolution, while also spanning multiple spatial and/or temporal scales. Importantly, NIH is looking for tools that can work in any brain region and, ideally, throughout the full depth of the brain, addressing long-standing challenges like accessing deep structures, maintaining signal quality, minimizing invasiveness, and scaling up measurements without losing resolution.

A major theme of the announcement is high-risk, high-reward engineering and science. The agency explicitly anticipates that proposed work may be risky and technically ambitious, but it prioritizes approaches that, if successful, would remove major barriers that slow neurobiological experiments and limit discovery. The expected payoff is transformative: technologies that could change how researchers study the CNS, enabling experiments that reveal circuit mechanisms underlying behavior, cognition, sensation, and disease-relevant processes.

The FOA covers both recording and modulation, and it is broad about what "signals" count. While classic electrophysiology and neuronal spiking are within scope, NIH also encourages technologies that use or read out other modalities such as optical, magnetic, acoustic, and genetic methods, and that can target not only neurons but also non-neuronal cells (for example glia and other supporting cell types) and networks. On the modulation side, the announcement encompasses stimulation or activation, inhibition, and more general manipulation approaches, including multimodal strategies that combine reading and writing of neural activity in coordinated ways.

To keep the work grounded in realistic neuroscience use-cases, NIH expects proposed technologies to be compatible with experiments in behaving animals and to be validated under in vivo experimental conditions. In other words, the focus is not just on a benchtop prototype, but on demonstrating that the method can function in living systems in a way that neuroscientists can actually use for experiments that involve behavior. Proposals that integrate multiple approaches are specifically encouraged, reflecting the idea that the biggest advances often come from combining innovations in hardware, chemistry, biology, and data analysis rather than relying on a single technique.

Because these projects can be highly interdisciplinary, applicants are expected, when appropriate, to assemble teams that cover the necessary expertise. The FOA calls out integration across biological, chemical, and physical sciences, along with engineering, computational modeling, and statistical analysis. This signals that strong applications will often include not only a device or method, but also rigorous plans for analysis, modeling, quantification of performance, and clear validation benchmarks relevant to neuroscience experiments.

The funding mechanism is an NIH R01 grant, categorized as a discretionary grant program in health-related research (CFDA numbers listed include 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, and 93.866). Clinical trials are not allowed under this announcement, reinforcing that the intended outcomes are enabling technologies and foundational capabilities rather than clinical testing.

Eligibility is broad and includes many organization types. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other categories. The FOA also highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). This wide eligibility reflects an intent to draw in innovators from many sectors and communities, including institutions that may bring unique perspectives, engineering strengths, or underserved-area research capacity.

Key administrative details from the source data include the agency (NIH), the opportunity category (discretionary), the funding instrument (grant), and the creation date (2021-06-08). The original closing date listed is 2023-02-08. The award ceiling and the expected number of awards are not specified in the provided data, which typically means applicants need to consult the full FOA or NIH budget guidance for institute-specific expectations and constraints.

In practical terms, a strong proposal under this opportunity would read like a technology-driven neuroscience plan: it would define a major unmet need in recording and/or modulation, present a creative solution that goes beyond incremental improvements, lay out measurable performance targets (for example resolution, depth, coverage, speed, stability, specificity, or invasiveness), and demonstrate a credible path to in vivo validation in behaving animals. It would also explain how the new capability reduces barriers for the broader community and opens doors to experiments that could not be done before, which is the central motivation of this BRAIN Initiative technology program.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed)" 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.
• This funding opportunity was created on 2021-06-08.
• Applicants must submit their applications by 2023-02-08. (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.

Apply for RFA NS 21 026

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