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

Frequently Asked Questions (FAQs)

What is this NIH funding opportunity?

This opportunity is an NIH Notice of Funding Opportunity (NOFO) titled "Integrated Functional Mapping and Molecular Profiling of Cell Ensembles Encoding the Effects of Addictive Substances in Rodents (R01 Clinical Trial Not Allowed)" with funding opportunity number RFA-DA-25-023.

What is the main goal of the program?

The program supports research projects that 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. A core goal is to create integrated, cell-by-cell reference maps that connect what cells do during drug-related behaviors with what those same cells are (their molecular type/state), where they are located, and how they are connected in circuits.

What kind of grant mechanism is this?

This is an R01 research project grant.

Are clinical trials allowed under this opportunity?

No. The NOFO is explicitly "Clinical Trial Not Allowed," meaning the work should be preclinical and conducted in rodents rather than human clinical intervention studies.

What species or model system is the NOFO focused on?

The focus is on rodent models, with research aimed at understanding how addictive substances affect neuronal/cellular ensembles and related behaviors and brain states in rodents.

What types of research questions fit this NOFO?

Projects should move beyond measuring either brain activity or molecular identity alone. The emphasis is on integrated approaches that link ensemble activity during drug-related behaviors to molecular identity and state, anatomical position, and circuit wiring, building reference-grade maps that are useful across the field.

What does the NOFO mean by "cell ensembles" in this context?

In this NOFO, "cell ensembles" refers to specific groups of cells (often neuronal ensembles) whose collective activity patterns encode behavioral and brain-state effects of addictive substances.

What does "multimodal integration" mean here?

Multimodal integration means combining multiple measurement types and connecting them at single-cell resolution, ideally from the same cells. The goal is not just to collect different data types, but to link them so ensemble activity can be interpreted in terms of cell identity, plasticity state, circuit role, and anatomical organization.

Does the NOFO prioritize collecting multiple data types from the same cells?

Yes. A major priority is true multimodal integration from the same cells at single-cell resolution, connecting population-scale activity dynamics measured during behavior with molecular and anatomical features measured on those identical cells.

What kinds of activity measurements are relevant?

The NOFO highlights population-scale measurements of cellular activity dynamics in behaving rodents, including large-scale recordings or imaging approaches that track activity patterns during behavior.

What complementary modalities are specifically called out?

Examples of desired complementary modalities include transcriptomic class (gene-expression-based cell types), epigenetic state (regulatory changes reflecting experience or drug exposure), connectivity (synaptic and pathway participation), and spatial localization (precise anatomical position).

Is the program limited to small, localized brain samples?

No. The NOFO emphasizes workflows that are innovative and scalable, capable of handling large numbers of cells and broad, distributed brain networks rather than small, localized samples.

What does it mean to "inventory" and "register" ensembles across the brain?

In practical terms, this means identifying relevant cells, aligning them to anatomical frameworks, and making the resulting data comparable across animals, experiments, and laboratories.

What stages of substance exposure or addiction-related behavior are in scope?

The scope spans multiple stages, including acute exposure, chronic exposure, withdrawal, abstinence, and relapse. The intent is to capture how ensemble membership and function change over time, not just what is active at one snapshot.

What is the expected overarching deliverable from funded projects?

The NOFO emphasizes producing high-quality, reference-grade multimodal datasets that the broader research community can use to build new descriptive and predictive models of addiction.

What does the NOFO mean by "descriptive" models?

"Descriptive" refers to clarifying which ensembles are involved, how they are distributed across brain regions, and how their activity patterns relate to behavioral states associated with addiction.

What does the NOFO mean by "predictive" models?

"Predictive" refers to enabling models that can anticipate state transitions (for example, vulnerability to relapse) or infer how molecular or circuit-level features shape ensemble dynamics.

What agency is offering this opportunity?

The agency is the National Institutes of Health (NIH).

What is the CFDA number listed for this opportunity?

The CFDA number provided is 93.279.

What is the funding activity category?

The funding activity category is listed under Education and Health.

What is the award ceiling for this opportunity?

The posted award ceiling is $700,000.

When is the application due?

The original application due date listed is 2026-02-23.

Who is eligible to apply?

Eligibility is broad and includes 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.

Are specific institution types explicitly mentioned as eligible?

Yes. The NOFO calls out additional eligible 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.

Are non-U.S. (foreign) entities eligible?

Yes. Non-U.S. (foreign) entities are included in the eligibility list as described.

What kinds of teams does this opportunity target?

The opportunity targets teams capable of combining advanced neural recording or imaging in behaving rodents with single-cell molecular profiling and circuit/anatomical mapping, with an emphasis on producing integrated datasets that clarify how distributed ensembles encode the effects of addictive substances across the addiction cycle.

Is the NOFO more about technology development, dataset generation, or both?

Based on the description, the NOFO emphasizes innovative and scalable technologies and workflows, and it also emphasizes generating high-quality, reference-grade multimodal datasets that can be broadly used by the field.

Does the program expect cross-animal or cross-lab comparability?

Yes. The NOFO emphasizes registering ensembles to anatomical frameworks and making the data comparable across animals, experiments, and laboratories.

Does the NOFO require linking function to identity and circuitry?

Yes. The central theme is to connect what cells do during drug-related behaviors (activity dynamics) with what those cells are (molecular type and state), where they are located (spatial localization/anatomy), and how they are wired (connectivity/circuit participation).