Highlight: Slicing Optional
CLARITY provided this 3-D view showing a thick slice of a mouse brain’s memory hub, or hippocampus. It reveals a few different types of cells: projecting neurons (green), connecting interneurons (red), and layers of support cells, or glia (blue). Conventional 2-D methods require that brain tissue be thinly sliced, sacrificing the ability to analyze such intact components in relation to each other.
Source: Kwanghun Chung, Ph.D., and Karl Deisseroth, M.D., Ph.D., Stanford University
Until recently, researchers studying the brain’s fine structure and connections faced tradeoffs. To probe deeply and with high enough resolution to analyze cells, molecules, and genes, researchers had to slice brain tissue into thin sections— making it hard to relate fine structure to more macro-level information about wiring and circuitry. Enter Karl Deisseroth, M.D., Ph.D., of Stanford University and colleagues. By replacing the fat that normally holds the brain’s working components in place with a clear gel, these researchers made the brain’s normally opaque and impenetrable tissue transparent and permeable. This opens the intact post-mortem brain to the same kind of chemical, genetic, and optical analyses that used to require slicing—while preserving the brain’s 3-D structure and the integrity of its circuitry and other biological machinery. The technique—CLARITY (Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue Hydrogel)—promises to transform the way scientists study the brain’s anatomy and how disease changes it.20
“CLARITY will help support integrative understanding of large-scale, intact biological systems. It provides access to subcellular proteins and molecules, while preserving the continuity of intact neuronal structures such as long-range circuit projections, local circuit wiring, and cellular spatial relationships."
Karl Deisseroth, M.D., Ph.D., Stanford University
Highlight from Strategic Objective 1