Models of Purkinje cell dendritic tree selection during early cerebellar development

摘要

We investigate the relationship between primary dendrite selection of Purkinje cells and migration of their presynaptic partner granule cells during early cerebellar development. During postnatal development, each Purkinje cell grows more than three dendritic trees, from which a primary tree is selected for development, whereas the others completely retract. Experimental studies suggest that this selection process is coordinated by physical and synaptic interactions with granule cells, which undergo a massive migration at the same time. However, technical limitations hinder continuous experimental observation of multiple cell populations. To explore possible mechanisms underlying this selection process, we constructed a computational model using a new computational framework, NeuroDevSim. The study presents the first computational model that simultaneously simulates Purkinje cell growth and the dynamics of granule cell migrations during the first two postnatal weeks, allowing exploration of the role of physical and synaptic interactions upon dendritic selection. The model suggests that interaction with parallel fibers is important to establish the distinct planar morphology of Purkinje cell dendrites. Specific rules to select which dendritic trees to keep or retract result in larger winner trees with more synaptic contacts than using random selection. A rule based on afferent synaptic activity was less effective than rules based on dendritic size or numbers of synapses. 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 two primary dendrites. However, this neuron has multiple similar trees during development, and retracts most of them and keeps its primary tree. At the same time the most numerous neuron type in the brain, cerebellar granule cells, migrate from their place of birth on top of Purkinje cells to a final location below. We focused on interactions of the axons of these granule cells with growing Purkinje dendrites as criteria to select the surviving dendritic tree, hypothesizing that developing an efficient network with other neurons is a main goal of neuronal morphology. We constructed and used computational models to investigate detailed physical interactions and communications between Purkinje and granule cells that are difficult to study experimentally during early postnatal stages.