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 multiscale 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. Although 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 that regions with larger and more complex pyramidal cells to have more macroscale corticocortical connections. In this study, 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 magnetic resonance imaging (human). Across these three mammalian species, we show cortical variation in neural organization to be associated with 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.