Reid Lab

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 and ultimately the entire brain. 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.

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.

The Reid lab at Harvard began a research program in connectomics in the early years of the field, in 2006. We concentrated on the visual system, with the first connectomics study of the cerebral cortex along with calcium imaging of visual responses (Bock et al, 2011, followed by Lee et al, 2016). At the Allen Institute, the Connectomics Department continued with this research program as participants in the IARPA MICrONS program. The MICrONS cubic millimeter dataset resulted in a suite of papers in Nature in 2025.

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