Part 1. Overview Information

Participating Organization(s) National Institutes of Health (NIH)

Components of Participating Organizations

• NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS)
• National Eye Institute (NEI)
• National Institute on Aging (NIA)
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• National Institute of Biomedical Imaging and Bioengineering (NIBIB)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• National Institute on Deafness and Other Communication Disorders (NIDCD)
• National Institute on Drug Abuse (NIDA)
• National Institute of Mental Health (NIMH)
• National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

• Office of Behavioral and Social Sciences Research (OBSSR)

Funding Opportunity Title BRAIN Initiative: Integrative Team-Research BRAIN Circuits Program - iBCP (RM1 Clinical Trial Not Allowed)

Activity Code RM1 Research Project with Complex Structure

Announcement Type Reissue of RFA-NS-22-028

Related Notices

• Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON) RFA-NS-27-002

Companion Funding Opportunity None

Number of Applications See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 93.372, 93.853, 93.286, 93.173, 93.279, 93.865, 93.242, 93.213, 93.866, 93.273, 93.867

Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) supports transdisciplinary research teams seeking to develop mechanistic, biologically grounded explanations of how neural circuits and their cellular building blocks give rise to central nervous system (CNS) function. Teams must integrate expertise spanning molecular and cellular through systems neuroscience, with strong collaboration between experimental and computational investigators, to bridge cells, circuits, and behavior in a unified framework that yields mechanistic insight.

Applications must explicitly connect three core elements: (1) characterization of circuit components (e.g., cell types and/or connectivity); (2) measurement of dynamic circuit activity, incorporating in vivo CNS recordings at cellular and sub-second temporal resolution; and (3) analyses of a tractable behavior or functional output.

To address this significant challenge in neuroscience, proposed studies are expected to leverage innovative conceptual or theoretical frameworks, predictive models, and/or cutting-edge approaches that unify these three levels of analysis and bridge experimental and computational components.

Recipients are expected to participate in BRAIN consortia activities to identify standards of practice towards multi-level integration.

Funding Opportunity Goal(s) To provide extramural research support for the Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative's aim of revolutionizing our understanding of the brain and its function in unprecedented detail. The NIH BRAIN Initiative's focus is foundational development of new technologies and tools to map, monitor, and modulate brain circuits in model systems and humans – toward the ultimate goal of treating and curing human brain disorders.

Key Dates

• Posted Date: August 31, 2026
• Open Date (Earliest Submission Date): September 07, 2026

Application Due Dates

Application Due Dates	Review and Award Cycles	AIDS - New/Renewal/Resubmission/Revision, as allowed	Scientific Merit Review	Advisory Council Review	Earliest Start Date
October 07, 2026	Not Applicable	Not Applicable	March 2027	May 2027	July 2027
June 23, 2027	Not Applicable	Not Applicable	November 2027	January 2028	April 2028
June 23, 2028	Not Applicable	Not Applicable	November 2028	January 2029	April 2029

All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Expiration Date: June 24, 2028

Due Dates for E.O. 12372: Not Applicable

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Table of Contents

• Part 1. Overview Information
• Key Dates
• Part 2. Full Text of Announcement
• Section I. Notice of Funding Opportunity Description
• Section II. Award Information
• Section III. Eligibility Information
• Section IV. Application and Submission Information
• Section V. Application Review Information
• Section VI. Award Administration Information
• Section VII. Agency Contacts
• Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

BACKGROUND The BRAIN Initiative Since 2014, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders.

As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN Initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas and was updated and enhanced in 2019 to: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This and other BRAIN Initiative Notices of Funding Opportunities (NOFOs) are based on this vision and issued with input from Advisory Councils of the 10 NIH Institutes and Centers supporting the BRAIN Initiative, as assisted by the NIH BRAIN Multi-Council Working Group and Neuroethics Working Group.

The NIH BRAIN Initiative recognizes innovative ideas require creativity, scientific expertise, and experience along with scientific collaboration. There are many benefits that flow from a scientific workforce with team participation including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, and enhancing public trust.

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, BRAIN consortia activities, and the BRAIN Initiative Biennial Conference. The data sharing expectations for BRAIN Initiative awards can be found at BRAIN Data Knowledge Resources.

The Integrated BRAIN Circuits Program (iBCP): An Overview The iBCP aims to understand how the nervous system gives rise to mental experience and behavior. A multi-level understanding of central nervous system (CNS) function is essential for identifying critical circuits involved in health and disease, and for advancing our ability to monitor and modulate neural circuits for both basic and translational applications.

Despite rapid advances in molecular, cellular, systems, and computational neuroscience, achieving a comprehensive understanding of brain function remains hindered by persistent methodological, conceptual, and disciplinary barriers within and between different levels of analysis. Technically, for example, fully mapping and interpreting the activity patterns of heterogeneous cell types with sub-millisecond temporal resolution in behaving animals remains a challenge. Conceptually, insights into how cellular heterogeneity and connectivity relate to dynamic neural processes and computations that underpin behavior remain limited. Moreover, scientific progress often occurs in disciplinary silos, hampering integration across levels of analysis.

The BRAIN Initiative fosters cross-disciplinary collaboration, yet transdisciplinary integration that enables, for example, a comprehensive linking of cellular components to circuit function and behavior, remains a major hurdle. While molecular and cellular neuroscience offers detailed "parts lists" and targeted manipulation tools, the role of cellular heterogeneity in complex neural computations is not well understood. Conversely, systems neuroscience provides powerful methods for analyzing population-level dynamics but often lacks the cell-type specificity necessary for mechanistic insight.

The iBCP directly addresses this challenge by emphasizing the need for dynamic circuits- and systems-level investigations that incorporate emerging knowledge and data on circuit components, including cell types and connectivity. As this is a significant challenge in neuroscience, the BRAIN Initiative now seeks to support development of innovative conceptual and theoretical frameworks, and cutting-edge approaches, both experimental and computational, to understand brain function holistically, from its circuit components to behavior output.

Deliverables from this effort are expected to advance our ability to investigate and understand how the CNS encodes, processes, and transmits information across spatial (cell to brain region) and temporal (milliseconds to behavioral timescales) dimensions. These will also lead to mechanistic, biologically grounded explanations of CNS function, ultimately revealing how cellular-level interventions produce circuit- and behavior-level effects and offering new targets and insights for treating dysfunction.

Program Expectations Teams of 3–6 PDs/PIs are expected to combine distinct areas of expertise ranging from molecular and cellular to circuits to systems neuroscience, with strong interactions between experimentalists and computational neuroscientists, to pursue a single Specific Aim of developing mechanistic explanations of how neural circuits give rise to behavior and/or defined CNS functions.

A mechanistic insight is defined as an explanation of how defined circuit components and their dynamic activity and/or interactions causally generate CNS function, yielding predictive and testable hypotheses. To achieve this, applications are expected to explicitly integrate the following three levels of analysis (see Section IV for details on how each of these levels is defined):

1. Behavior. Behavior represents the functional output of nervous system activity and provides the essential context for interpreting neural circuit function. Anchoring cellular and circuit-level measurements to a well-defined behavior or clearly defined physiological measures of behavior enables causal links between neural activity, computation, and function, which are critical for understanding both normal brain processes and dysfunction.
2. Circuits. Circuit analysis at the level of population activity during behaviors provides the bridge between cellular properties and behavioral outcomes. This level reveals how neural signals evolve over time, how information flows within and across circuits, and how these dynamics shape behavior.
3. Circuit components. Neural circuits are composed of heterogeneous cell types with distinct roles within networks and characterized by distinct molecular identities, connectivity patterns, morphology, and/or physiological properties. It remains a challenge to identify which and how these components are critical for specific computations or behaviors.

The approach is expected to be driven by innovative conceptual or theoretical frameworks, predictive models, and/or cutting-edge methodologies that unify these three levels of analysis, bridge experimental and computational components, and use BRAIN-developed tools or resources where appropriate. The scale, complexity, and impact of this effort should reflect the transformative nature of the BRAIN Initiative. A successful program will deliver both mechanistic insights and broadly useful solutions to the challenges of bridging these levels of analysis.

This NOFO welcomes the use of a wide range of species, from invertebrate to human studies, including comparative approaches and the use of new approach methodologies (NAMS), with the requirement that these are chosen based on their power to address the specific question at hand and to reveal generalizable and fundamental principles.

Cross-species approaches to investigate generalizability are welcome. At least one species under study is expected to fully integrate all three levels of analysis (circuit components, dynamic circuit activity, and behavior). Other species may be included even if technical limitations prevent accessing all three levels.

Recipients are expected to actively participate in BRAIN Initiative consortium activities aimed at developing, harmonizing, and disseminating standards of practice that facilitate rigorous multi-level integration across cellular, circuit, and behavioral analyses.

Representative (not exhaustive) examples of integrative neuroscience research responsive to this NOFO:

Topics:

• Elucidating how heterogeneous CNS cell types contribute to the dynamic computations underlying behavior or functional output of the circuit (e.g., sensory, motor, cognition, social behavior, internal state, affective, brain-body physiology).
• Neural computations underlying distributed representation and information processing across brain regions during cognitive processes.
• Understanding how behavioral states are emergent properties of the interaction of neurons, circuits, and networks.
• Understanding the role of interactions between neuronal and non-neuronal cells in shaping neurocircuit function and behavior.
• Leveraging developmental processes to understand how cell type heterogeneity and circuit formation and organization contribute to function across life stages.
• Understanding the cellular basis of circuit reconfiguration or plasticity during learning, adaptation, or behavioral state transitions.
• Modeling flexible, goal-directed, or context-dependent behavior through frameworks that incorporate dynamic cellular contributions and network-level computation.

Approaches:

• Using comparative or evolutionary approaches to identify conserved circuit motifs or principles across species that inform general rules of CNS function.
• Using cellular and circuit analyses to generate computational models that are predictive of mechanisms of CNS function and behavior.
• Developing approaches that bridge across spatial (from single cells to networks) and temporal (from milliseconds to behavioral timescales) scales to understand dynamic neural computations that underlie behavior.
• Forming connection across levels of abstraction, by bringing mechanistic approaches, causal explanations, and biological constraints to the rich descriptive observations and/or normative models of brain function
• Developing generalizable analytic or modeling tools that can be applied across systems to facilitate integrative, multi-level analyses.
• Combining cutting-edge tools (e.g., multi-area imaging, electrophysiology, optogenetics, connectomics, single-cell omics) to relate cellular identity with circuit dynamics and behavior.
• Leveraging disease-related perturbations to provide mechanistic insights into normal CNS function and behavior.

Consultation with relevant Program Staff: Potential applicants should consult with the NOFO contact about responsiveness to the NOFO priorities, single research aim, team composition, and anticipated scope very early in the planning stage and a minimum of 8 weeks prior to the application due date. Staff will not assess technical or scientific merit; this will be determined during peer review using the criteria in this NOFO.

Applications that exhibit any of the following characteristics will be considered non-responsive and withdrawn from consideration:

• Primarily focuses on disease mechanisms, therapeutics, or treatments. Although disease-related perturbations may be employed to probe causality, such approaches are allowed only for elucidating fundamental mechanisms of CNS function. This NOFO does not support studies that are explicitly disease-focused; such proposals should be directed to the appropriate NIH IC.
• Fails to investigate and integrate these three levels of analysis (circuit components-dynamic circuits-behavior) in at least one of the species under study
• Does not include in vivo CNS recordings of neural population activity at cellular resolution, with sub-second temporal precision, acquired during the expression of the behavior or behaviorally relevant physiological correlate.
• Does not incorporate cell-type information at a level of heterogeneity or scale appropriate to the CNS function being investigated (e.g., limited to analysis of only one or two cell types)
• Does not integrate experimental and computational components
• Applications primarily consisting of collecting large-scale datasets without a clear plan to use these data to generate mechanistic insights

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed New

Clinical Trial? Not Allowed: Only accepting applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards NIH BRAIN Initiative intends to commit up to $8M per fiscal year to fund up to 5 awards.

Award Budget Application budgets need to reflect the actual needs of the proposed project. It is anticipated that most awards will not exceed $1M direct costs per fiscal year.

Award Project Period The scope of the proposed project should determine the project period. The maximum project period is 5 years

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

• Higher Education Institutions - Includes all types
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
• Nonprofits Other Than Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
• Local Governments
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Foreign Organizations/Foreign Collaborations

• Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.
• Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
• Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
• NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.
• Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

The application is required to be submitted as a multiple PD/PI application, with 3–6 PDs/PIs who have complementary expertise.

Section IV. Application and Submission Information

*(content truncated for brevity; see original HTML for full details)

Section V. Application Review Information

*(content truncated for brevity)

Section VI. Award Administration Information

*(content truncated for brevity)

Section VII. Agency Contacts

*(content truncated for brevity)

Section VIII. Other Information

*(content truncated for brevity)