How the molecular dynamics in axons shape presynaptic response
1 IEECR
Understanding how neurons regulate their protein composition to refine their synaptic connections across millimetres of space can provide insights into the mechanism of plasticity. The discovery of local protein synthesis in subcellular compartments has illustrated how neuronal activity can meet the metabolic demands of synaptic plasticity locally. However, such research in axons remains experimentally challenging due to their long and complex branches. We thus developed an in silico approach to pinpoint the factors that markedly impact mRNA localization along the axon of a typical pyramidal neuron. We investigated the contribution of dynamical factors such as diffusion, active transport and degradation in maintaining baseline counts of mRNA along a linear axon with one presynaptic bouton at the end. We characterized this relationship with an endogenous distribution describing the spatial profile and introduced a bias of anterograde active mRNA transport motivated by experimental reports. Using a broad range of values, we found a bimodal distribution of mRNA between the soma and the tip that was determined by the above factors. A higher degradation rate relative to the transport velocity rate led to a higher somatic accumulation and vice-versa, while a higher diffusion rate led to a more evenly-spaced mRNA concentration along the axon. Our approach integrates multiple molecular dynamical processes with axonal morphology. Identifying causal factors for the baseline mRNA distribution can serve as an indicator of conducting new experiments for studying animal models of disease. In the future, we intend to extend the analysis to include the induction of synaptic plasticity.