Whole human-brain mapping of single cortical neurons for profiling morphological diversity and stereotypy

Quantifying neuron morphology and distribution at the whole brain scale is
essential to understand the structure and diversity of cell types. It is
exceedingly challenging to reuse recent technologies of single cell
labeling and whole brain imaging to study human brains. We propose
Adaptive Cell Tomography (ACTomography), a low-cost, high-throughput,
high-efficacy tomography approach, based on adaptive targeting of
individual cells. We established a platform to inject dyes into cortical
neurons in surgical tissues of 18 patients with brain tumors or other
conditions and 1 donated fresh postmortem brain. We collected 3-D images
of 1746 cortical neurons, of which 852 neurons were reconstructed to
quantify local dendritic morphology, and mapped to standard atlases. In
our data, human neurons are more diverse across brain regions than by
subject age or gender. The strong stereotypy within cohorts of brain
regions allows generating a statistical tensor-field of neuron morphology
to characterize anatomical modularity of a human brain.