title: Wiring cost and topological participation of the mouse brain connectome.
abstract: 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.
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge CB2 3EB, United Kingdom; Churchill College, University of Cambridge, Cambridge CB3 0DS, United Kingdom; mr572@cam.ac.uk.
authors.forename: Mikail
authors.initials: M
authors.lastname: Rubinov
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge CB2 3EB, United Kingdom; Hughes Hall, University of Cambridge, Cambridge CB1 2EW, United Kingdom;
authors.forename: Rolf J F
authors.initials: RJ
authors.lastname: Ypma
authors.affiliation: Neuroscience Research Australia, University of New South Wales, Sydney NSW 2031, Australia; Faculty of Health Sciences, Curtin University, Kent Street, Bentley, WA 6102, Australia;
authors.forename: Charles
authors.initials: C
authors.lastname: Watson
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge CB2 3EB, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Huntingdon PE29 3RJ, United Kingdom; Alternative Discovery and Development, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
mesh_terms: D000818:Animals; D063132:Connectome; D020869:Gene Expression Profiling; D051379:Mice; D009415:Nerve Net / Q000502:physiology*
keywords: conservation law; cytoarchitectonics; graph theory; transcriptomics; viral tracing