The Armamentarium for Precision Brain Cell Access is developing a collection of molecular genetic reagents to gain access to many different brain cell types. The expanded collection of Armamentarium tools will aid neuroscientists in studying circuits in laboratory animals and human tissue specimens. These technologies have the potential to transform neuroscience research by bringing the precision of molecular targeting to specific neural circuits that underlie behavior and network function.
With these reagents, molecular genetic probes can be addressed to specific cell types not only to map circuits but also to monitor and manipulate neural activity. The precise and reproducible access to these circuit components enables the functional relevance of cell types in behavior to be explored in detail. The cause-and-effect relationships of cell types defined by recent brain cell census efforts and behavior can be delineated using targeted probes. Electrode- and neuroimaging-based technologies have greatly informed the understanding of the brain. Cell type-specific targeted probes from the Armamentarium hold promise to drive new discoveries about brain function. The cellular resolution and potential brain-wide scale of access will aid in uncovering new insights about brain circuits.
Gaining access to brain cell types using genetically engineered animals, like transgenic mice, has led to considerable progress in understanding circuits. But different tools are needed for use in less genetically tractable organisms, such as non-human primates. Brain cell type-selective access tools that are non-transgenic (e.g., engineered viral vectors) are needed for these species, which are important for understanding the human brain and behavior. Engineering hundreds of these reagents and disseminating them to neuroscientists are the focus of the Armamentarium. In the future, these types of precision targeting tools could be used in strategies to access human disease-relevant circuits to deliver gene therapies, gene editing tools, or circuit therapeutic technologies.
The Armamentarium encompasses multiple efforts supported by the following funding opportunities. With this support, which began in 2021, researchers are: (1) developing molecular genetic access reagents for specific brain cell types, (2) optimizing functional probes to be delivered as payloads by the access tools, (3) disseminating reagents widely to neuroscience researchers, and (4) building research infrastructure for cutting-edge technologies at historically under-resourced institutions.
“BRAIN Initiative: Reagent Resources for Brain Cell Type-Specific Access and Manipulation to Broaden Distribution of Enabling Technologies for Neuroscience” (U24 Clinical Trial Not Allowed) [RFA-MH-21-180]
The Armamentarium for Precision Brain Cell Access is one of three NIH BRAIN Initiative transformative projects outlined in The BRAIN Initiative® 2.0: From Cells to Circuits, Toward Cures report. Together with the BRAIN Initiative Cell Atlas Network (BICAN) and the BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS) Network, these large-scale projects promise to transform neuroscience research, illuminating foundational principles governing the circuit basis of behavior and informing new approaches to the treatment of human brain disorders.