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Reissue of RFA-NS-18-020: Understanding the dynamic activity of brain circuits is central to the NIH BRAIN Initiative. This FOA seeks applications for proof-of-concept testing and development of new technologies and novel approaches for recording and modulation (including various modalities for stimulation/activation, inhibition and manipulation) of cells (i.e., neuronal and non-neuronal) and networks to enable transformative understanding of dynamic signaling in the central nervous system (CNS). This FOA seeks exceptionally creative approaches to address major challenges associated with recording and modulating CNS activity, at or near cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. It is expected that the proposed research may be high-risk, but if successful, could profoundly change the course of neuroscience research. Proposed technologies should be compatible with experiments in behaving animals, validated under in vivo experimental conditions, and capable of reducing major barriers to conducting neurobiological experiments and making new discoveries about the CNS. Technologies may engage diverse types of signaling beyond neuronal electrical activity such as optical, magnetic, acoustic and/or genetic recording/manipulation. Applications that seek to integrate multiple approaches are encouraged. If suitable, applications are expected to integrate appropriate domains of expertise, including biological, chemical and physical sciences, engineering, computational modeling and statistical analysis.

Reissue of RFA-NS-18-019: Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. The invention, proof-of-concept investigation, and optimization of new technologies through iterative feedback from end users are key components of the BRAIN Initiative. This FOA seeks applications to optimize existing or emerging technologies through iterative testing with end users. The technologies and approaches should have potential to address major challenges associated with recording and modulation (including various modalities for stimulation/activation, inhibition and manipulation) of cells (i.e., neuronal and non-neuronal) and networks to enable transformative understanding of dynamic signaling in the central nervous system (CNS). These technologies and approaches should have previously demonstrated their transformative potential through initial proof-of-concept testing and are now ready for accelerated refinement. In conjunction, the manufacturing techniques should be scalable towards sustainable, broad dissemination and user-friendly incorporation into regular neuroscience research.Proposed technologies should be compatible with experiments in behaving animals, validated under in vivo experimental conditions, and capable of reducing major barriers to conducting neurobiological experiments and making new discoveries about the CNS. Technologies may engage diverse types of signaling beyond neuronal electrical activity such as optical, electrical, magnetic, acoustic or genetic recording/manipulation. Applications that seek to integrate multiple approaches are encouraged. If suitable, applications are expected to integrate appropriate domains of expertise, including biological, chemical and physical sciences, engineering, computational modeling and statistical analysis.

This NOSI supports creation of data archive(s), development of software tools, and establishment of data standards for BBQS-related studies to address the above-described challenges in the research program. The informatics infrastructure and tools to be developed under this NOSI are expected to be widely used by BBQS investigators, as well as by a broader community. Applications in response to this NOSI should therefore clearly justify the importance and implications of the proposed informatics infrastructure or tools to the BBQS program, and identify the potential user base. The projects funded under this NOSI are expected to support, communicate and collaborate with the funded BBQS research projects. Applicants should therefore familiarize themselves with the BBQS research program and funded projects (https://www.braininitiative.nih.gov/funding/initiatives.htm; also see RFA-MH-22-240 and RFA-DA-23-030).

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at revolutionizing neuroscience through development and application of innovative technologies to map neural circuits, monitor and modulate their activity, and understand how they contribute to thoughts, sensations, emotions, and behaviors. NIH has issued a variety of Funding Opportunity Announcements (FOAs) that will support projects that apply technologies to understand neural circuit function in the context of specific circuits, resulting in a diverse portfolio of research into the fundamental biology of nervous system function.

This FOA solicits the development of theories, computational models, and analytical tools to derive understanding of brain function from complex neuroscience data. Proposed projects could develop tools to integrate existing theories or formulate new theories; conceptual frameworks to organize or fuse data to infer general principles of brain function; multiscale/multiphysics models to generate new testable hypotheses to design/drive future experiments; new analytical methods to either support or refute a stated hypothesis about brain function. It is expected that the tools developed under this FOA will be made widely available to the neuroscience research community for their use and modification. Investigative studies should be limited to model parameter estimation and/or validity testing of the tools being developed.

This BRAIN Initiative FOA is to further develop molecular tools of high impact that are targetable to brain cell types for the monitoring and manipulation of neural circuits in experimental animals. This FOA is part of the BRAIN Initiative Armamentarium for Brain Cell Access transformative project. This will support iterative improvement of molecular payloads capable of monitoring and manipulating neural cell activity and that can be delivered to specific brain cell types using targeting technologies.

This FOA will support integrated, interdisciplinary research teams that focus on examining dynamic circuit functions related to behavior, using advanced and innovative technologies. The FOA will support programs with a necessarily-synergistic, team science approach. Awards will be made for 5 years, with a possibility of one competing renewal. Applications should incorporate overarching principles of circuit function in the context of specific neural systems underlying sensation, perception, emotion, motivation, cognition, decision-making, motor control, communication, or homeostasis. Applications should incorporate theory-/model-driven experimental design and should offer predictive models as deliverables. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Applications are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate. Applications will be required to manage their data and analysis methods in a framework that will be developed and used in the proposed U19 project and exchanged with other BRAIN U19 awardees for further refinement and development. Model systems, including the possibility of multiple species ranging from invertebrates to humans, can be employed and should be appropriately justified. Programs should employ multi-component teams of research expertise including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration. Applicants proposing to include human subjects with invasive neural recording must apply to the companion FOA, RFA-NS-XX-XXX.

This FOA will support integrated, interdisciplinary research teams from prior BRAIN technology and/or integrated approaches teams, and/or new projects from the research community that focus on examining circuit functions related to behavior, using advanced and innovative technologies. The goal will be to support programs with a team science approach that can realize meaningful outcomes within 5-plus years. Awards will be made for 5 years, with a possibility of one competing renewal. Applications should address overarching principles of circuit function in the context of specific neural systems underlying sensation, perception, emotion, motivation, cognition, decision-making, motor control, communication, or homeostasis. Applications should incorporate theory-/model-driven experimental design and should offer predictive models as deliverables. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Applications are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate. Applications will be required to manage their data and analysis methods in a prototype framework that will be developed and used in the proposed U19 project and exchanged with other U19 awardees for further refinement and development. Model systems, including the possibility of multiple species ranging from invertebrates to humans, can be employed and should be appropriately justified. Budgets should be commensurate with multi-component teams of research expertise including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration.

This FOA will support integrated, interdisciplinary research teams that focus on examining dynamic circuit functions related to behavior, using advanced and innovative technologies. The FOA will support programs with a necessarily-synergistic, team science approach. Awards will be made for 5 years, with a possibility of one competing renewal. Applications should focus on overarching principles of circuit function in the context of specific neural systems underlying sensation, perception, emotion, motivation, cognition, decision-making, motor control, communication, or homeostasis. Applications should aim to understand these circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Applications are expected to employ approaches and experimental design guided by specified theoretical constructs, are encouraged to employ quantitative, mechanistic and predictive models where appropriate. Model systems, including the possibility of multiple species ranging from invertebrates to humans, can be employed and should be appropriately justified. Programs should employ multi-component teams of research expertise including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration. Applications will be required to manage their data and analysis methods in a framework that will be developed and used in the proposed U19 project and exchanged with other BRAIN U19 awardees for further refinement and development.

This is a reissue of RFA-MH-21-135. This FOA supports the development of software to visualize and analyze the data as part of programs of building the informatics infrastructure for the BRAIN Initiative. Other informatics programs include developing data standards that are needed to describe the new experiments that are being created by or used in the BRAIN Initiative ( RFA-MH-19-146 ), and creating the data infrastructures that will house the data from multiple experimental groups ( RFA-MH-19-145 ). Each of the programs is aimed at building an infrastructure that is used by a particular sub-domain of experimentalists rather than building a single all-encompassing informatics infrastructure now. Building the infrastructure one experimental area at a time will ensure that the infrastructure is immediately useful to components of the research community. As our understanding of the brain improves, it may be possible to create linkages between these various sub-domain specific informatics programs. Investigators of the informatics programs should keep that goal in mind and build for the future even though the current efforts are more limited in scope.