A framework for modeling the growth and development of neurons and networks

The development of neural tissue is a complex organizing process, in which it is difficult to grasp how the various localized interactions between dividing cells leads relentlessly to global network organization. Simulation is a useful tool for exploring such complex processes because it permits rigorous analysis of observed global behavior in terms of the mechanistic axioms declared in the simulated model. We describe a novel simulation tool, CX3D, for modeling the development of large realistic neural networks such as the neocortex, in a physical 3D space. In CX3D, as in biology, neurons arise by the replication and migration of precursors, which mature into cells able to extend axons and dendrites. Individual neurons are discretized into spherical (for the soma) and cylindrical (for neurites) elements that have appropriate mechanical properties. The growth functions of each neuron are encapsulated in set of pre-defined modules that are automatically distributed across its segments during growth. The extracellular space is also discretized, and allows for the diffusion of extracellular signaling molecules, as well as the physical interactions of the many developing neurons. We demonstrate the utility of CX3D by simulating three interesting developmental processes: neocortical lamination based on mechanical properties of tissues; a growth model of a neocortical pyramidal cell based on layer-specific guidance cues; and the formation of a neural network in vitro by employing neurite fasciculation. We also provide some examples in which previous models from the literature are re-implemented in CX3D. Our results suggest that CX3D is a powerful tool for understanding neural development.