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Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain


Douglas S. Kim, Ph.D.
Office of Technology Development and Coordination


This concept aims to continue a BRAIN Initiative program that supports technology development to probe cell- and circuit-specific processes in the brain (RFA-MH-19-136 ). Relating cognition and behavior of humans and other animals to the functions of specific brain cells and circuits is challenging. Progress in this effort has been limited in part by the complexity, scale, and speed of brain networks. The goal of this concept is to continue supporting research on new technologies for the analysis of brain cells and circuits with greater clarity, scalability, and precision. This work may enable further study of brain circuitry underlying behavior.


The "BRAIN 2025: A Scientific Vision " report recommends comprehensive efforts for "Discovering Diversity" and making "Maps at Multiple Scales" in the brain. This concept aims to continue supporting technology development to map, monitor, and manipulate the diverse components of brain circuits. For example, there has been support for improved methods for molecular access to neural cells, high-resolution sensing of neuronal states, in situ gene expression profiling, and synthetic receptors for perturbing neuronal activity. Moreover, this program has supported new technologies for anatomical reconstruction of developing and mature circuits at the cellular, subcellular, and synaptic levels. These new and improved tools for probing circuits with cellular resolution are intended to aid in the study of basic neuroscience questions and potentially disease-relevant processes in the brain.

This concept aims to continue supporting the development of cell and circuit probing technologies with an emphasis on advancing capabilities further. Researchers would be encouraged to create or substantially improve existing technologies to facilitate analysis of circuits that underlie brain function. The focus would continue to be on mapping, monitoring, and manipulation methods with neural cell-type and/or circuit-level specificity. Improved technologies are still needed to study both the structure and function of circuit components with greater clarity, scalability, and precision. Technologies that can contribute to multiple areas of neuroscience and are potentially applicable across relevant species are a priority. Continued validation of technologies developed through this concept would also to be encouraged. The effort may contribute methods to transform the identification of neural cell diversity, defined access to neural cell types, and characterization of circuit connectivity. The ultimate goal is to foster a set of technologies to delineate a comprehensive structural view of brain circuits at cellular resolution and to create a dynamic picture of brain cell function in the context of behavior.