Multiscale symbolic morpho-barcoding reveals region-specific and scale-dependent neuronal organization

Neuronal morphology shapes circuit organization, yet its multiscale complexity has hindered systematic brain-wide analysis. Here, we introduce multiscale morpho-barcoding (MMB), a framework that encodes whole-brain neuronal morphology into symbolic barcodes spanning cellular geometry, axonal tract routing, arbor organization, and predicted presynaptic distributions. Applying MMB to 1,876 fully reconstructed mouse neurons, comprising 3,776 arbors, and 2.63 million predicted presynaptic sites, we identified distinct multiscale morpho-patterns that help reveal two organizational principles. First, neuronal morphology is region specific: regional identity arises from distinct combinations of shared and region-biased morpho-motifs. Second, organization is scale dependent: different morphological scales contribute differentially to the neuronal classification and circuit architecture. Within this mouse dataset, MMB discriminates major anatomical divisions and resolves canonical thalamic circuit classes, exceeding the resolution of projection strength-based representations. MMB provides an interpretable and scalable framework for integrating morphology with connectivity and function. This framework could further be applicable to analyze disease-oriented structural phenotypes.

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Publication Details

Journal
Cell Reports
Published
2026-07-25
DOI
https://doi.org/10.1016/j.celrep.2026.117712
Primary Topic
Cell Image Analysis Techniques
Type
article
Field-Weighted Citation Impact
0.00

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article

Multiscale symbolic morpho-barcoding reveals region-specific and scale-dependent neuronal organization

Sujun Zhao, Yufeng Liu, Hanchuan Peng, Yingxin Li
Cell Reports
Cell Image Analysis Techniques
article

Multiscale symbolic morpho-barcoding reveals region-specific and scale-dependent neuronal organization

Sujun Zhao, Yufeng Liu, Hanchuan Peng, Yingxin Li
article en

Abstract

Neuronal morphology shapes circuit organization, yet its multiscale complexity has hindered systematic brain-wide analysis. Here, we introduce multiscale morpho-barcoding (MMB), a framework that encodes whole-brain neuronal morphology into symbolic barcodes spanning cellular geometry, axonal tract routing, arbor organization, and predicted presynaptic distributions. Applying MMB to 1,876 fully reconstructed mouse neurons, comprising 3,776 arbors, and 2.63 million predicted presynaptic sites, we identified distinct multiscale morpho-patterns that help reveal two organizational principles. First, neuronal morphology is region specific: regional identity arises from distinct combinations of shared and region-biased morpho-motifs. Second, organization is scale dependent: different morphological scales contribute differentially to the neuronal classification and circuit architecture. Within this mouse dataset, MMB discriminates major anatomical divisions and resolves canonical thalamic circuit classes, exceeding the resolution of projection strength-based representations. MMB provides an interpretable and scalable framework for integrating morphology with connectivity and function. This framework could further be applicable to analyze disease-oriented structural phenotypes.

Cell ReportsVol. 45(8)
Allen Institute for Brain Science (US), Fudan University (CN), Southeast University (CN)
Southeast University
Openalex Percentile: Top 10%
Cell Image Analysis Techniques
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