Density-dependence of functional development in spiking cortical   networks grown in vitro
  During development, the mammalian brain differentiates into specialized regions with distinct functional abilities. While many factors contribute to functional specialization, we explore the effect of neuronal density on the development of neuronal interactions in vitro. Two types of cortical networks, dense and sparse, with 50,000 and 12,000 total cells respectively, are studied. Activation graphs that represent pairwise neuronal interactions are constructed using a competitive first response model. These graphs reveal that, during development in vitro, dense networks form activation connections earlier than sparse networks. Link entropy analysis of dense net- work activation graphs suggests that the majority of connections between electrodes are reciprocal in nature. Information theoretic measures reveal that early functional information interactions (among 3 cells) are synergetic in both dense and sparse networks. However, during later stages of development, previously synergetic relationships become primarily redundant in dense, but not in sparse networks. Large link entropy values in the activation graph are related to the domination of redundant ensembles in late stages of development in dense networks. Results demonstrate differences between dense and sparse networks in terms of informational groups, pairwise relationships, and activation graphs. These differences suggest that variations in cell density may result in different functional specialization of nervous system tissue in vivo. 
Michael I. Ham, Vadas Gintautas, Marko A. Rodriguez, Ryan A. Bennett,   Cara L. Santa Maria, Luis M.A. Bettencourt