Name: Whole-neuron morphology and genetic identity define cell types and reveal principles of brain-wide cortical connectivity
Published: 2026

Whole-neuron morphology and genetic identity define cell types and reveal principles of brain-wide cortical connectivity

[ DOI: https://doi.org/10.35077/g.1198 ]

Dataset Citation:

Hongkui, Zeng, Wang, Yun. (2026). Whole-neuron morphology and genetic identity define cell types and reveal principles of brain-wide cortical connectivity. [ Collection / Dataset ]. Brain Image Library. https://doi.org/10.35077/g.1198

Methods:

Neuron sparse labeling was achieved using transgenic mouse lines combined with viral drivers and reporters. Many expression patterns are available in the AIBS Transgenic Characterization database (http://connectivity.brain-map.org/transgenic/search/basic). Cre driver lines were crossed with GFP reporters to enable sparse, robust labeling of genetically defined populations. Whole-brain imaging at high resolution (0.35 × 0.35 × 1 µm; ~11,000 sections per brain) generated terabyte-scale datasets preserving dendritic and axonal morphology. From these data, we reconstructed 1,418 cortical excitatory neurons from 79 brains across 25 transgenic lines, primarily sampling 15 cortical areas.

TechnicalInfo:

Apical dendritic, basal dendritic, and axonal features were extracted from SWC files of studied cells using in-house Arboreta’s neuron_statistics.exe, and for calculating projected axon lengths, using in-house NeuronMetrics, an implementation of neuron_statistics.exe.

Abstract:

Neocortex contains diverse excitatory neurons whose dendritic and axonal architectures shape computation and long-range communication, yet a unified framework linking neuronal structure, molecular identity, and brain-wide connectivity is lacking. Here, we combine complete whole-neuron morphology (WNM) reconstructions with paired genetic identities across 15 cortical areas to define organizing principles of cortical wiring at single-cell resolution. We identify ten stable excitatory cell types with conserved morphology and predominant genetic correspondence. Their axonal target spectra reveal four output architectures and cell-type- resolved principles of corticocortical and cortico-subcortical organization, including conserved cell types across regions, modular convergence in downstream targets, distinct spatial topographical rules across projection pathways, and hierarchical organization better predicted by targeting probability and projection distribution than projection strength, while refining bulk-derived projectomes by resolving artifacts from bulk approaches. Together, these findings establish whole-neuron morphology as a principled axis for defining cortical cell types as building blocks of large-scale connectomes.

Funding:

National Institutes of Health U19-MH114830 A comprehensive whole-brain atlas of cell types in the mouse;
National Institutes of Health U01-NS132267 BRAIN CONNECTS: PatchLink, scalable tools for integrating connectomes, projectomes, and transcriptomes

Contributors:

Hongkui, Zeng (ProjectLeader) [ORCID: https://orcid.org/0000-0002-0326-5878 ] Allen Institute for Brain Science
Wang, Yun (DataCollector) [ORCID: https://orcid.org/0000-0001-5501-8433 ] Allen Institute for Brain Science

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