Computational models of developing neural systems

Thework of this thesis has focused on creating computational models of developing neurons. Three different but related areas of research have been studied how cells make connections, what influences the shape of these connections and how neuronal network behaviour can be influenced by local interactions. In order to understand how cells make connections I simulated the dynamics of the neuronal growth cone a structure which guides the developing axon to its target cells. Results from the first models showed that small interaction effects between structural proteins in the axon called microtubules can significantly alter the rate of axonal elongation and turning. I also simulated the dynamics of growth cone filopodia. The filopodia act as antennae and explore the extracellular environment surrounding the growth cone. This model showed that a reaction-diffusion system based on Turing morphogenesis patterns could account for the dynamic behaviour of filopodia. To find out what influences the shape of neuronal connections I simulated the branching patterns of neuronal dendrites. These are tree-like structures which receive input from other cells. Recent experiments indicate that dendrite branching is dependent on the phosphorylation status of microtubule associated protein 2 (MAP2)which affects the growth rate and spacing ofmicrotubules. MAP2phosphorylation can occur through calcium activation of the protein CaMKII. In the model the phosphorylation status and physical distribution of MAP2within the cell can be varied to produce a wide range of biologically realistic dendritic patterns. The final model simulates emergent synchronisation of neuronal spike firing which can occur in cultures of developing neurons. In the model the frequency and phase of cell firing is modified by the pattern of input signals received by the cell through local connections. This mechanism alone can lead to synchronous oscillation of the entire network of cells. The results of the model indicate that synchronization of firing in developing neurons in culture occurs through a passive spread of activity, rather through an active coupling mechanism.