Modeling the Co-existence of NMDAR-Dependent and AMPAR-Regulated Long-Term Potentiation/Depression

In this work, we develop a mathematical model that captures both the early and late phases of Long-Term Potentiation (LTP) and Long-Term Depression (LTD) within an NMDAR-dependent and AMPA-regulated framework. The model combines multiple essential properties. First, it emphasizes a detailed representation of biochemical processes within the postsynaptic neuron, thereby illustrating the interaction between LTD and distinct forms of LTP. Second, the dynamic modulation of postsynaptic AMPA receptor conductance is represented through nonlinear differential equations and algebraic relations. Third, the model incorporates input specificity, associativity, and cooperativity, allowing synaptic changes at one site to influence the strength of neighboring synapses. These features provide a comprehensive description of synaptic dynamics, allowing the simulation of plasticity at both the cellular and the network levels. Overall, the model offers a valuable framework for studying NMDAR-dependent LTP and LTD by explicitly incorporating AMPA currents. We believe that this model provides deeper insights into the molecular mechanisms of synaptic plasticity and paves the way for the construction of network-level models by linking multiple cells through AMPA receptor conductance.