Comprehensive computational modelling of the development of mammalian cortical connectivity underlying an architectonic type principle
The architectonic type principle attributes patterns of cortico-cortical connectivity to the relative architectonic differentiation of cortical regions. One mechanism through which the observed close relation between cortical architecture and connectivity may be established is the joint development of cortical areas and their connections in developmental time windows. Here, we describe a theoretical exploration of the possible mechanistic underpinnings of the architectonic type principle, by performing systematic computational simulations of cortical development. The main component of our in silico model was a developing two-dimensional cortical sheet, which was gradually populated by neurons that formed cortico-cortical connections. To assess different explanatory mechanisms, we varied the spatiotemporal trajectory of the simulated histogenesis. By keeping the rules governing axon outgrowth and connection formation constant across all variants of simulated development, we were able to create model variants which differed exclusively by the specifics of when and where neurons were generated. Thus, all differences in the resulting connectivity were due to the variations in spatiotemporal growth trajectories. Our results demonstrated that a prescribed targeting of interareal connection sites was not necessary for obtaining a realistic replication of experimentally observed connection patterns. Instead, we found that spatiotemporal interactions within the forming cortical sheet were sufficient if a small number of empirically well-grounded assumptions were met, namely planar, expansive growth of the cortical sheet around two points of origin as neurogenesis progressed, stronger architectonic differentiation of cortical areas for later neurogenetic time windows, and stochastic connection formation. Our study pinpointed potential mechanisms of how relative architectonic differentiation and cortical connectivity become linked during development. The successful prediction of connectivity in two species, cat and macaque, from simulated cortico-cortical connection networks further underscored the general applicability of mechanisms through which the architectonic type principle can explain cortical connectivity in terms of the relative architectonic differentiation of cortical regions.\n\nAuthor SummaryThe mechanisms that govern the establishment of cortico-cortical connections during the development of the mammalian brain are not completely understood. In computational simulation experiments reported here, we explored the foundations of an architectonic type principle, which attributes adult cortical connectivity to the relative architectonic differentiation of connected areas. Architectonic differentiation refers, among other characteristics, to the cellular make-up of cortical areas. This architectonic type principle has been found to account for diverse properties of cortical connectivity across mammalian species. Our in silico model generated connectivity patterns consistent with the architectonic type principle and typically observed in mammalian cortices, if model settings were chosen such that they corresponded to empirical observations about how cortical development proceeds. Our computational experiments systematically evaluated previously proposed mechanisms of cortical development and showed that connectivity consistent with the architectonic type principle arises only from realistic assumptions about the growth of the cortical sheet.