Dissecting origins of wiring specificity in dense cortical connectomes

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Abstract

The organization of synaptic connections between neurons shapes the computations performed by cortical circuits. Understanding the principles governing this organization requires dissecting the contributions of different factors to synaptic specificity. Here, we analyze dense electron microscopy reconstructions of cortical tissue to identify the origins of wiring specificity. We develop a computational framework that separates the contributions of neuronal morphology, spatial proximity, and cell-type-specific connectivity rules to the observed connectivity patterns. Our analysis reveals that while spatial proximity and morphological constraints explain a substantial fraction of connectivity, cell-type-specific rules add critical specificity that cannot be explained by geometry alone. We identify systematic deviations from random connectivity that vary across cell types and cortical layers, suggesting functionally specialized wiring motifs. These findings provide insights into how evolution and development shape cortical circuits to support computation, and offer constraints for biologically realistic models of cortical networks.

Citation

@article{harth2024dissecting,
  title={Dissecting origins of wiring specificity in dense cortical connectomes},
  author={Harth, Philipp and Udvary, Daniel and Boelts, Jan and Baum, Daniel and Macke, Jakob H and Hege, Hans-Christian and Oberlaender, Marcel},
  journal={bioRxiv},
  year={2024},
  publisher={Cold Spring Harbor Laboratory}
}