AMPAR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, is a receptor concentrated at the postsynaptic density (PSD) of dendritic spines. AMPAR is often used as a readout for synaptic plasticity since increased AMPAR density at the PSD leads to a stronger synaptic response to a stimulus while decreased AMPAR density leads to a weaker response. Changes in AMPAR density during synaptic plasticity involve numerous complex signaling pathways, many of which have been studied both experimentally and computationally. However, there are still open questions regarding how the dynamics of several key components upstream of AMPAR, including CaMKII and phosphatase dynamics, influence the mechanisms and dynamics of AMPAR trafficking. Here we construct both a deterministic compartmental ordinary differential equations model and a deterministic reaction-diffusion model of the simplified signaling network underlying AMPAR dynamics during synaptic plasticity to probe how upstream kinase and phosphatase dynamics influence AMPAR dynamics and trafficking. We find that key signaling components and trafficking mechanisms act over different timescales to modulate AMPAR density at the PSD. In particular, AMPAR temporal dynamics show two timescales associated with endo/exocytosis and total available AMPAR sources, while there is a strong relationship between total AMPAR number at the PSD and the spine volume to surface area ratio.

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