VIDEO ABSTRACT.

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Decoding the human brain is perhaps the most fascinating scientific challenge in the 21st century. The Human Brain Project (HBP), a 10-year European Flagship, targets the reconstruction of the brain's multi-scale organization. It uses productive loops of experiments, medical, data, data analytics, and simulation on all levels that will eventually bridge the scales. The HBP IT architecture is unique, utilizing cloud-based collaboration and development platforms with databases, workflow systems, petabyte storage, and supercomputers. The HBP is developing toward a European research infrastructure advancing brain research, medicine, and brain-inspired information technology.

Correct positioning of cortical neurons during development depends on the radial migration of the projection neurons and on the coordinated tangential and radial migrations of the subcortically generated interneurons. As previously shown, a transient and moderate maternal deficiency in thyroxin during early corticogenesis alters the radial migration of projection neurons. To determine if a similar effect might also affect tangential migration of medial ganglionic eminence (MGE)-derived neurons at the origin of cortical interneurons, explants of MGE from green fluorescent protein (GFP)-transgenic embryos were implanted into flat cortical mounts from wild-type embryos. The distances covered and the preferential migration (medially) of GFP-MGE neurons from embryos of hypothyroxinemic dams are not affected in their tangential migration into wild-type control cortices. In contrast, when GFP-MGE neurons from embryos of control or hypothyroxinemic dams migrate within cortices from embryos of hypothyroxinemic dams, the GFP-MGE-derived neurons lose their preferential direction of migration, although they still migrate for long distances throughout the cortex. Our results show that maternal hypothyroxinemia alters the tangential migration of GFP-MGE-derived neurons in the neocortex of the progeny and suggest that this alteration is not derived from the migratory neurons themselves but through undefined short- and long-range cues responsible for the guidance of their migration.

The organization of connectivity in neuronal networks is fundamental to understanding the activity and function of neural networks and information processing in the brain. Recent studies show that the neocortex is not only organized in columns and layers but also, within these, into synaptically connected clusters of neurons (Ko et al., 2011; Perin et al., 2011). The recently discovered common neighbor rule, according to which the probability of any two neurons being synaptically connected grows with the number of their common neighbors, is an organizing principle for this local clustering. Here we investigated the theoretical constraints for how the spatial extent of neuronal axonal and dendritic arborization, heretofore described by morphological reach, the density of neurons and the size of the network determine cluster size and numbers within neural networks constructed according to the common neighbor rule. In the formulation we developed, morphological reach, cell density, and network size are sufficient to estimate how many neurons, on average, occur in a cluster and how many clusters exist in a given network. We find that cluster sizes do not grow indefinitely as network parameters increase, but tend to characteristic limiting values.