Imaging brain tissue architecture across millimeter to nanometer scales

Area of Science:

• Neuroscience
• Cell Biology
• Microscopy

Background:

• Mapping brain architecture requires nanoscale resolution for cellular and synaptic details.
• Super-resolution microscopy offers molecular insights but lacks tissue-wide context.
• Existing methods struggle to bridge the gap between regional and synaptic scales.

Purpose of the Study:

• To develop a technology for dense mapping of brain tissue architecture across multiple scales.
• To enable 3D reconstruction and connectivity analysis of neural circuits.
• To demonstrate the applicability of the technology to diverse brain preparations, including human samples.

Main Methods:

• Developed Comprehensive Analysis of Tissues across Scales (CATS) technology.
• Utilized fixation-compatible extracellular labeling and advanced optical imaging (STED/ExM).
• Enabled 3D reconstruction of synapses and mapping of synaptic clefts.

Main Results:

• Densely mapped brain tissue architecture from millimeter to nanometer scales.
• Reconstructed and quantified synaptic input/output structures in mouse hippocampus.
• Demonstrated CATS applicability to formalin-fixed paraffin-embedded human brain tissue.

Conclusions:

• CATS technology enables comprehensive nanoscale mapping of brain tissue architecture.
• The method bridges the gap between cellular and synaptic resolution in diverse samples.
• CATS has potential applications in understanding brain health and disease.