A blueprint of mammalian cortical connectomes

The cerebral cortex of mammals exhibits intricate interareal wiring. Moreover, mammalian cortices differ vastly in size, cytological composition, and phylogenetic distance. Given such complexity and pronounced species differences, it is a considerable challenge to decipher organizational principles of mammalian connectomes. Here, we demonstrate species-specific and species-general unifying principles linking the physical, cytological, and connectional dimensions of architecture in the mouse, cat, marmoset, and macaque monkey. The existence of connections is related to the cytology of cortical areas, in addition to the role of physical distance, but this relation is attenuated in mice and marmoset monkeys. The cytoarchitectonic cortical gradients, and not the rostrocaudal axis of the cortex, are closely linked to the laminar origin of connections, a principle that allows the extrapolation of this connectional feature to humans. Lastly, a network core, with a central role under different modes of network communication, characterizes all cortical connectomes. We observe a displacement of the network core in mammals, with a shift of the core of cats and macaque monkeys toward the less neuronally dense areas of the cerebral cortex. This displacement has functional ramifications but also entails a potential increased degree of vulnerability to pathology. In sum, our results sketch out a blueprint of mammalian connectomes consisting of species-specific and species-general links between the connectional, physical, and cytological dimensions of the cerebral cortex, possibly reflecting variations and persistence of evolutionarily conserved mechanisms and cellular phenomena. Our framework elucidates organizational principles that encompass but also extend beyond the wiring economy principle imposed by the physical embedding of the cerebral cortex. Author summary The cerebral cortex is wired in a highly intricate manner and exhibits striking differences across mammalsfor instance, in overall size and number of neurons. Here, we uncover common, but also species-specific, principles that link the physical, cellular, and connectional architecture of mouse, cat, and monkey brains. Commonalities allow the extrapolation of features to further, unexamined species, such as humans, whereas the species-specific principles point at potential functional differences, but also varied degrees of vulnerability, of mammalian brains. The observed unifying principles may reflect variations of evolutionarily conserved neurodevelopmental mechanisms. In sum, we sketch out a blueprint of mammalian cortical organization that elucidates the links between the physical, cytological, and connectional architecture. Our results indicate that caution is warranted when translating findings from one mammalian species to another, since some, but not all, cortical organizational properties are common across the mammalian spectrum.