Cell Reports
Volume 34, Issue 5, 2 February 2021, 108709
Journal home page for Cell Reports

Resource
Chemical sectioning fluorescence tomography: high-throughput, high-contrast, multicolor, whole-brain imaging at subcellular resolution

https://doi.org/10.1016/j.celrep.2021.108709Get rights and content
Under a Creative Commons license
open access

Highlights

  • Chemical sectioning enables wide-field based blockface imaging with high resolution

  • The CSFT method is compatible with the multicolor imaging of FP-labeled samples

  • CSFT enables whole-brain imaging of single-neuron anatomy at subcellular resolution

Summary

A thorough neuroanatomical study of the brain architecture is crucial for understanding its cellular compositions, connections, and working mechanisms. However, the fine- and multiscale features of neuron structures make it challenging for microscopic imaging, as it requires high contrast and high throughput simultaneously. Here, we propose chemical sectioning fluorescence tomography (CSFT) to solve this problem. By chemically switching OFF/ON the fluorescent state of the labeled proteins (FPs), we light only the top layer as thin as submicron for imaging without background interference. Combined with the wide-field fluorescence micro-optical sectioning tomography (fMOST) system, we have shown multicolor CSFT imaging. We also demonstrate mouse whole-brain imaging at the subcellular resolution, as well as the power for quantitative acquisition of synaptic-connection-related pyramidal dendritic spines and axon boutons on the brain-wide scale at the complete single-neuron level. We believe that the CSFT method would greatly facilitate our understanding of the brain-wide neuron networks.

Keywords

chemical sectioning fluorescence tomography
whole-brain imaging
subcellular resolution
multicolor imaging
high-contrast
high-throughput

Cited by (0)

5

These authors contributed equally

6

Lead contact