Clay Reid

Tracing individual axons
through the human brain.

The Reid lab has launched a new research program to map long-range projection axons through human white matter at the scale of centimeters — something never achieved before. Using post-mortem human tissue, dense antibody staining, tissue expansion, and light-sheet fluorescence microscopy, the lab is characterizing the 3D trajectories and architectural organization of individual myelinated axons across regions of the entire brain.

Figure 2. Three architectural motifs in human white matter. (A–C) Grayscale axons labeled with neurofilament-H (NFH) antibodies: multi-orientation, laminar/orthogonal, and bundled. (D–F) Structure tensor color maps (red = ML, green = DV, blue = AP). (G–I) Orientation distribution functions.

bioRxiv · April 2026

Heterogeneity of white-matter organization in the human brain

Turschak E, Yu W-Q, Takasaki K, Cook SJ, Torres R, Gliko O, Hellevik A, Villalobos K, Guadarrama E, Chatterjee S, Perlman E, Laughland C, Glaser A, Sümbül U, Reid RC

White matter makes up nearly half the human brain, yet the 3D organization of individual axons has never been directly characterized. Using a histological pipeline optimized for post-mortem human tissue, this work reveals striking regional diversity — from loosely packed meshworks in superficial white matter to tightly packed parallel bundles in the corpus callosum.

These distinct motifs likely reflect local adaptations to spatial constraints, axonal density, and the diversity of sources and targets — offering region-specific solutions to anatomical optimization problems.

View on bioRxiv →

Human white matter
from slab to single axon.

The pipeline moves from post-mortem brain slabs to tissue punchouts, through expansion clearing, and into a custom ExA-SPIM lightsheet microscope — resolving individual axons at sub-micron voxels across centimeter-scale volumes.

Figure 1. (A) Fixed hemi-coronal brain slab with numbered punchout locations marked in yellow, alongside an Allen Institute atlas section. (B) 500 μm vibratome section. (C) Cleared tissue-hydrogel matrix after 3× expansion. (D) Confocal pre-expansion overview. (E) ExA-SPIM lightsheet image showing individual NFH-labeled axons (scale bar 100 μm).

Figure 3. Montage of four central punchouts (centrum semiovale, corpus callosum, cingulum bundle, basal ganglia region) with structure tensor color coding: red = medio-lateral, green = dorso-ventral, blue = antero-posterior. Panels B–H show three orthogonal views through 500×500×350 μm image stacks. Scale bar 1 mm (panel A).

More from the axonal
connectomics program.

EM connectomics &
the MICrONS program.

For many years the Reid lab was at the forefront of large-scale electron microscopy connectomics, producing some of the most complete synaptic-resolution circuit maps ever assembled. This work — now continued by colleagues at the Allen Institute — culminated in the MICrONS cubic millimeter dataset and a suite of papers in Nature in 2025.

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