Cross-species evidence of interplay between neural connectivity at the micro- and macroscale of connectome organization in human, mouse and rat brain

The mammalian brain describes a multi-scale system. At the microscale, axonal, dendritic and synaptic elements ensure neuron-to-neuron communication, and at the macroscale, large-scale projections form the anatomical wiring for communication between cortical areas. While it is clear that both levels of neural organization play a crucial role in brain functioning, their interaction is not extensively studied. Connectome studies of the mammalian brain in cat, macaque and human have recently shown regions with larger and more complex pyramidal cells to have more macroscale corticocortical connections. Here, we aimed to further validate these cross-scale findings in the human, mouse and rat brain. We combined neuron reconstructions from the NeuroMorpho.org neuroarchitecture database with macroscale connectivity data derived from connectome mapping by means of tract-tracing (rat, mouse) and in vivo diffusion MRI (human). Across these three mammalian species we show cortical variation in neural organization to be associated to features of macroscale connectivity, with cortical variation in neuronal complexity explaining significant proportions of cortical variation in the number of white matter projections of cortical areas. Our findings converge on the notion of a relationship between features of micro- and macroscale neural connectivity to form a central aspect of mammalian neural architecture.