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Index: #1

Most Brain Circuitry is Still Invisible

Understanding the complete wiring of the brain at single–cell resolution, along with detailed molecular annotations, is critical for revealing how neural circuits support learning, memory, and behavior. Current technologies are prohibitively expensive and lack scalability, limiting our ability to link molecular composition with circuit connectivity and to understand the alterations present in brain disorders. This gap fundamentally makes diagnosis, treatment, and prevention of many brain disorders more difficult. Beyond the biomedical applications, maps of brain circuitry could play a fundamental role in grounding principles of safety for brain-like AI systems. Initiatives like the NIH BRAIN Initiative’s transformative projects (the BRAIN Initiative Cell Atlas Network (BICAN), the BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS) Network, and the Armamentarium for Precision Brain Cell Access) represent important efforts to illuminate foundational principles governing the circuit basis of behavior and to inform new approaches to treating human brain disorders by radically enhancing our understanding of brain cell types and the tools needed to access them (The BRAIN Initiative® 2.0: From Cells to Circuits, Toward Cures).

Foundational Capabilities (3)

Combine advanced imaging methods—such as synchrotron X–ray microscopy and expansion microscopy—to rapidly and scalably image neural circuits in both small and large brain regions. This method promises high spatial resolution with faster throughput.
Develop new physical detection methods for electron microscopy that improves scalability of visualization of brain circuitry.