This Notice of Funding Opportunity (NOFO) seeks applications to optimize instrumentation and device technologies for recording and modulation of neural cells and circuits, to address major challenges and to enable transformative understanding of dynamic signaling in the central nervous system. It is expected that the proposed technologies and approaches have previously demonstrated their transformative potential through initial proof-of-concept testing, and are ready for accelerated refinement through iterative engineering and end-user feedback, appropriate for a path towards sustainable dissemination and user-friendly incorporation into routine neuroscience research. Applications may propose development of instrumentation hardware and/or devices and associated software. Approaches may utilize any modality such as optical, electrical, magnetic, or acoustic recording/manipulation, to target neuronal electrical signals or other forms of neural activity, including intracellular signaling and engagement of non-neuronal cells in circuit function. This NOFO is a re-issue of RFA-NS-21-027, but unlike the previous NOFO the focus is narrowed to technologies associated with recording/manipulation instrumentation and devices, and excludes projects primarily focused on development of molecular reagents. Potential applicants primarily optimizing molecular constructs should consider RFA-MH-22-245 (or its reissue), BRAIN Initiative: Engineering and optimization of molecular technologies for functional dissection of neural circuits (UM1 Clinical Trial Not Allowed). For projects at an earlier stage of development of molecular reagents, potential applicants should consider the companion FOA (RFA-NS-25-018) or alternative BRAIN Initiative announcements including RFA-MH-21-175 and RFA-EY-21-001 (or their reissues). For this and the companion NOFO, the aim of the proposed technologies should be to reduce major barriers to conducting neurobiological experiments, including considerations of cost and ease of access, and to enable new discoveries for understanding neural circuit function. Technologies should address major challenges associated with recording and modulating CNS activity, at cellular or circuit resolution, and should contribute to an overall ecosystem of technologies spanning multiple spatial and temporal scales in any region throughout the CNS. The approaches should be compatible with experiments in behaving animals, with an expectation that they will be validated with in vivo experiments during the course of the project. Proposed validation experiments must focus on demonstrating the capabilities and potential impact of the technology, rather than advancing the state of biological knowledge as the primary project goal. Applications are encouraged to integrate multiple approaches, and where appropriate, to leverage a variety of domains of expertise from biological, chemical, and physical sciences, engineering, computational modeling, and statistical analysis.

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