284579 Mathematical Modeling of Synaptic Vesicle Trafficking in C. Elegans
C. elegans, a soil dwelling nematode, is a highly studied multi-cellular organism that offers several experimental advantages, including a short life span, ease of culture and transparency, to name a few. Additionally, its full genome and neuronal wiring diagram are known. This, combined with current molecular biological techniques, make it an excellent model system for biological study, especially for neuroscience. Synaptic function, assembly and maintenance is one of the areas where C. elegans has become an ideal model system.
Synapse assembly and maintenance is determined in part by the transport of synaptic vesicles along microtubules that run along the axon and dendrite of neurons. Pre-synaptic regions are well-defined regions in the axon, where these vesicles preferentially dock onto active zones where synapses are created onto other neurons’ post-synaptic regions in the dendrite or muscles at the neuromuscular junction. Many players in the localization of such pre-synaptic regions have been identified, although the regulation of vesicle trafficking and its influence on the final location of active zones is far from understood. We generated a simple mathematical model to describe experimental data obtained for the dynamic transport of synaptic vesicle precursors in C. elegans obtained with neuron-wide time-lapse microscopy. The model describes synaptic vesicle transport in different regions of the neuron from a mass balance approach, and predicts that new, previously unexplored parameters are relevant for vesicle transport and distribution. Additionally, sensitivity analysis of the model hints at the most relevant parameters that ultimately determine transport and the final, steady state concentration of synaptic vesicles, as well as synapse location.