ABSTRACT
Mammalian neurons operate at length scales spanning five orders of magnitude; micron-scale-diameter myelinated axons project millimeters across brain regions, ultimately forming nanometer scale synapses on individual post-synaptic neurons. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities (e.g. MRI, electron microscopy, etc.). Translating between the different modalities, however, requires imaging the same brain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micron-scale synchrotron x-ray tomography (μCT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brain’s multi-scaled organization as well as a vehicle for studying the brain’s multi-scale pathologies.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
This version of the manuscript has been revised as follows: ∼600 words of text have been removed to adhere to formatting requirements for a technical note in NeuroImage. Neither the story nor the substance of the text has changed, though. Figure 5 caption was also corrected to remove typos.
6. ABBREVIATIONS
- MRI
- Magnetic Resonance Imaging
- DTI
- Diffusion tensor Imaging
- EM
- Automated Electron Microscopy
- μCT
- Synchrotron-based x-ray tomography