Integrated Functional Mapping and Molecular Profiling of Cell Ensembles Encoding the Effects of Addictive Substances in Rodents (R01 Clinical Trial Not Allowed) | RFA DA 25 023

Opportunity Information: Apply for RFA DA 25 023

This NIH grant opportunity, titled "Integrated Functional Mapping and Molecular Profiling of Cell Ensembles Encoding the Effects of Addictive Substances in Rodents (R01 Clinical Trial Not Allowed)" (RFA-DA-25-023), supports research projects that can systematically identify and characterize the specific groups of cells (often called neuronal or cellular ensembles) that encode the behavioral and brain-state effects of addictive substances in rodent models. The central idea is to move beyond measuring either brain activity or molecular identity in isolation, and instead build integrated, cell-by-cell "reference" maps that connect what cells do during drug-related behaviors with what those same cells are (their molecular type and state), where they are located, and how they are wired into circuits.

The NOFO emphasizes technologies and workflows that are both innovative and scalable, meaning they should be capable of handling large numbers of cells and broad, distributed brain networks rather than small, localized samples. Applicants are expected to "inventory" and "register" ensembles across the brain, which in practical terms means identifying the relevant cells, aligning them to anatomical frameworks, and making the data comparable across animals, experiments, and laboratories. The research focus spans multiple stages of substance exposure and addiction-relevant behavior, including acute exposure, chronic exposure, withdrawal, abstinence, and relapse. By covering these stages, the program aims to capture how ensemble membership and function change over time, not just what is active at a single snapshot.

A major priority is true multimodal integration from the same cells at single-cell resolution. The NOFO specifically highlights combining population-scale measurements of cellular activity dynamics in behaving rodents (for example, large-scale recordings or imaging approaches that track activity patterns during behavior) with more granular molecular and anatomical measurements on those identical cells. Examples of desired complementary modalities include transcriptomic class (gene-expression-based cell types), epigenetic state (regulatory changes that can reflect experience or drug exposure), connectivity (how cells are synaptically linked and which pathways they participate in), and spatial localization (precise anatomical position). The expectation is not merely to collect multiple data types, but to connect them in a way that allows investigators to interpret ensemble activity in terms of cell identity, plasticity state, circuit role, and anatomical organization.

The overarching deliverable is high-quality, reference-grade multimodal datasets that can be used broadly by the field to build new descriptive and predictive models of addiction. "Descriptive" in this context means clarifying which ensembles are involved, how they are distributed across brain regions, and how their activity patterns relate to behavioral states associated with addiction. "Predictive" means enabling models that can anticipate state transitions (for example, vulnerability to relapse) or infer how molecular or circuit-level features shape ensemble dynamics. The program is designed to push toward integrated frameworks where activity patterns, molecular phenotypes, and circuit architecture jointly explain addiction-associated neurobehavioral states.

Mechanistically, this is an R01 research project grant and is explicitly "Clinical Trial Not Allowed," indicating the work should be preclinical and conducted in rodents rather than human clinical intervention studies. The funding activity category is listed under Education and Health, and the CFDA number is 93.279. The agency is the National Institutes of Health. The posted award ceiling is $700,000, and the original application due date is 2026-02-23.

Eligibility is broad and includes many organization types: state, county, and local governments; 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 tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations other than small businesses; and small businesses. The NOFO also calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. (foreign) entities. Overall, the opportunity targets teams capable of combining advanced neural recording or imaging in behaving rodents with single-cell molecular profiling and circuit/anatomical mapping, producing integrated datasets that clarify how distributed ensembles encode the effects of addictive substances across the addiction cycle.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Integrated Functional Mapping and Molecular Profiling of Cell Ensembles Encoding the Effects of Addictive Substances in Rodents (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): 93.279.
• This funding opportunity was created on 2023-12-06.
• Applicants must submit their applications by 2026-02-23. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $700,000.00 in funding.
• 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 DA 25 023

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