Granule cells affect dendritic tree selection in purkinje cells during cerebellar development

Abstract

This study investigates the interrelationship between primary dendrite selection of Purkinje cells and migration of their pre-synaptic partner granule cells during cerebellar development. During development of the cerebellar cortex, each Purkinje cell grows more than three dendritic trees, from which a primary tree is selected to develop further, whereas the others completely retract. Experimental studies suggest that this selection process is coordinated by physical and synaptic interactions with granule cells. However, technical limitations hinder a continuous experimental observation of multiple populations. To reveal the mechanism underlying this selection process, we constructed a computational model of dendritic developments and granule cell migrations, using a new computational framework, NeuroDevSim. Comparisons of the resulting morphologies from the model demonstrate the roles of the selection stage in regulating the growth of the selected primary trees. The study presents the first computational model that simultaneously simulates growing Purkinje cells and the dynamics of granule cell migrations, revealing the role of physical and synaptic interactions upon dendritic selection. The model provides new insights about the distinct planar morphology of Purkinje cell dendrites and about roles of the dendritic selection process during the cerebellar development. The model also supports the hypothesis that synaptic interactions by granule cells are likely to be involved in the selection procedure. Author SummaryThe mature structure of a Purkinje cell, the main neuron of the cerebellum, is composed of a large flat dendritic tree composed of a single or sometimes 2 primary dendrites. However, this neuron has multiple similar trees during development, and retracts most of them to select its primary tree. We aim to explore roles of this developmental process as either an important step to attain optimal morphology or merely a redundant step to be eliminated by evolution in the future. We especially focused on environmental interactions on Purkinje cells as criteria to select the dendritic tree, hypothesizing that developing an efficient network with other neurons is one of the main goals of neuronal morphology. We constructed and used computational models to investigate detailed physical interactions and communications between Purkinje cells and their environment. Comparisons of models suggest the role of the selection stage is to obtain favorable growth of primary trees.