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Wiring cost and topological participation of the mouse brain connectome.



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Rubinov, Mikail 
Ypma, Rolf JF 
Watson, Charles 
Bullmore, Edward T 


Brain connectomes are topologically complex systems, anatomically embedded in 3D space. Anatomical conservation of "wiring cost" explains many but not all aspects of these networks. Here, we examined the relationship between topology and wiring cost in the mouse connectome by using data from 461 systematically acquired anterograde-tracer injections into the right cortical and subcortical regions of the mouse brain. We estimated brain-wide weights, distances, and wiring costs of axonal projections and performed a multiscale topological and spatial analysis of the resulting weighted and directed mouse brain connectome. Our analysis showed that the mouse connectome has small-world properties, a hierarchical modular structure, and greater-than-minimal wiring costs. High-participation hubs of this connectome mediated communication between functionally specialized and anatomically localized modules, had especially high wiring costs, and closely corresponded to regions of the default mode network. Analyses of independently acquired histological and gene-expression data showed that nodal participation colocalized with low neuronal density and high expression of genes enriched for cognition, learning and memory, and behavior. The mouse connectome contains high-participation hubs, which are not explained by wiring-cost minimization but instead reflect competitive selection pressures for integrated network topology as a basis for higher cognitive and behavioral functions.



conservation law, cytoarchitectonics, graph theory, transcriptomics, viral tracing, Animals, Connectome, Gene Expression Profiling, Mice, Nerve Net

Journal Title

Proc Natl Acad Sci U S A

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Proceedings of the National Academy of Sciences
Medical Research Council (G1000183)
Medical Research Council (G0001354)
Wellcome Trust (095844/Z/11/Z)
Wellcome Trust (093875/Z/10/Z)
Funding was provided by a NARSAD Young Investigator award and Isaac Newton Trust (to M.R.); a Rubicon Fellowship (to R.J.F.Y.); the Medical Research Council and the Wellcome Trust (Behavioural & Clinical Neuroscience Institute); and the National Institute for Health Research Cambridge Biomedical Research Centre (high-performance computing facilities).