Selective collateralization of transcriptomically distinct neurons organizes visual-stream output from the primary visual cortex
- 1Allen Institute, Brain Science
Abstract
Parallel visual streams segregate information into pathways specialized for distinct computations, but how this segregation is achieved by anatomical segregation of primary visual cortex output remains unclear. This problem is complicated because individual neurons frequently send broadcasting projections to multiple cortical areas, and the target choice depends on both topographical location and molecular identity. Here we developed axonal BARseq2 to jointly map gene expression and high-resolution axonal projections from 1,448 neurons spanning the mouse primary visual cortex (VISp). Axonal BARseq2 recapitulated projection patterns observed by bulk tracing and single-neuron reconstruction, and recovered transcriptomic identities consistent with reference snRNA-seq datasets. Retinotopy strongly predicted projections to individual cortical targets, particularly for areas proximal to VISp, but explained little of which areas are frequently co-innervated. Instead, co-innervation patterns defined three preferential output pathways that largely corresponded to the ventral stream and two subdivisions of the dorsal stream. These pathways were associated with fine-grained transcriptional identities of L4/5 intra-telencephalic neurons, which were further validated with an external MERFISH dataset. Thus, VISp output is organized by two distinct rules: retinotopy constrains where neurons project, whereas cell-type-associated collateralization constrains which targets are co-innervated. This selective broadcasting, in which single neurons reach many higher visual areas in cell-type-specific combinations, could provide an anatomical substrate for visual-stream segregation at the level of VISp output in mice.
Related
- Single-nucleus transcriptomics uncovers region-specific molecular features underlying selective aging vulnerability of cholinergic neurons
- Tunable neuronal microenvironments drive distinct functional phenotypes in human iPSCs-derived dopaminergic neurons
- Distinct properties of glutamate-dopamine, nonglutamate-dopamine, and glutamate-only ventral tegmental area neurons
- A fibril-selective single-domain antibody targets pathogenic amyloid-β assemblies and protects human neurons
- Visual-cortex-projecting neurons in mouse auditory cortex show distinct audiovisual responses independent of motor-related activity
BibTeX
@misc{majeed2026selective,
title = {{Selective collateralization of transcriptomically distinct neurons organizes visual-stream output from the primary visual cortex}},
author = {M. Majeed and M. C. P. Rue and A. Zhang and S. Cheng and J. Wang and S. Khem and A. Alaya and J. Ariza and O. Helbeck and K. Nguyen and B. Ouellette and A. Oyama and M. Reding and D. Rette and J. Weber and A. Williford and Y. Isogai and X. Chen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748541},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748541v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Selective collateralization of transcriptomically distinct neurons organizes visual-stream output from the primary visual cortex
AU - M. Majeed
AU - M. C. P. Rue
AU - A. Zhang
AU - S. Cheng
AU - J. Wang
AU - S. Khem
AU - A. Alaya
AU - J. Ariza
AU - O. Helbeck
AU - K. Nguyen
AU - B. Ouellette
AU - A. Oyama
AU - M. Reding
AU - D. Rette
AU - J. Weber
AU - A. Williford
AU - Y. Isogai
AU - X. Chen
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748541
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748541v1
AB - Parallel visual streams segregate information into pathways specialized for distinct computations, but how this segregation is achieved by anatomical segregation of primary visual cortex output remains unclear. This problem is complicated because individual neurons frequently send broadcasting projections to multiple cortical areas, and the target choice depends on both topographical location and molecular identity. Here we developed axonal BARseq2 to jointly map gene expression and high-resolution axonal projections from 1,448 neurons spanning the mouse primary visual cortex (VISp). Axonal BARseq2 recapitulated projection patterns observed by bulk tracing and single-neuron reconstruction, and recovered transcriptomic identities consistent with reference snRNA-seq datasets. Retinotopy strongly predicted projections to individual cortical targets, particularly for areas proximal to VISp, but explained little of which areas are frequently co-innervated. Instead, co-innervation patterns defined three preferential output pathways that largely corresponded to the ventral stream and two subdivisions of the dorsal stream. These pathways were associated with fine-grained transcriptional identities of L4/5 intra-telencephalic neurons, which were further validated with an external MERFISH dataset. Thus, VISp output is organized by two distinct rules: retinotopy constrains where neurons project, whereas cell-type-associated collateralization constrains which targets are co-innervated. This selective broadcasting, in which single neurons reach many higher visual areas in cell-type-specific combinations, could provide an anatomical substrate for visual-stream segregation at the level of VISp output in mice.
ER -