# Biological Basis of the Model Code The provided code is a computational model simulating synaptic transmission with an emphasis on NMDA receptor properties. This model builds upon the standard dual-exponential synaptic model (Exp2Syn) for synaptic conductance to include features specific to NMDA receptors, a critical component in synaptic plasticity, learning, and memory. ## Key Biological Concepts ### NMDA Receptors NMDA (N-methyl-D-aspartate) receptors are a type of ionotropic glutamate receptor found in neurons. They are unique in that their ion channel opening depends not only on the binding of glutamate but also on the membrane voltage. This voltage-dependence is largely due to a magnesium (Mg²⁺) block that must be removed for the channel to conduct ions like calcium (Ca²⁺), sodium (Na⁺), and potassium (K⁺). ### Voltage-Dependent Magnesium Block The model explicitly incorporates the voltage-dependent Mg²⁺ block of NMDA receptors. At resting membrane potentials, the channel pores are typically blocked by Mg²⁺ ions. Depolarization of the neuron ejects Mg²⁺ from the channel, allowing ion flow. The function `vspom(v)` models this voltage dependence of the Mg²⁺ block with three variations, reflecting different experimental findings: - **Maex and De Schutter (1998)**: Implements a specific exponential relationship between voltage and Mg²⁺ unblock. - **Harnett et al. (2012)**: Offers another experimental perspective on Mg²⁺ block, as input by a different parameterization. - **Jahr & Stevens (1990)**: Provides yet another modelling approach based on historical research on the dynamics of NMDA receptor Mg²⁺ block. ### Synaptic Kinetics The model describes the kinetics of synaptic currents using a dual exponential approach (`Exp2Syn`). The rise (`tau1`) and decay (`tau2`) time constants are parameters influencing how fast the conductance rises to its peak and then decays, mimicking synaptic response properties. The `NET_RECEIVE` block allows the conductance states (A and B) to change in response to synaptic inputs, simulating neurotransmitter release. ### Conductance Calculation The resultant synaptic current `i` is calculated based on the conductance `g`, the NMDA receptor Mg²⁺ block (`mgBlock`), and the difference between the membrane potential (`v`) and the reversal potential (`e`). ### External Magnesium Concentration The `extMgConc` parameter allows the model to incorporate changes in extracellular Mg²⁺ concentration, affecting the degree of the Mg²⁺ block. ## Biological Relevance This model is designed to simulate the behavior of NMDA receptor-mediated synapses accurately, capturing key properties such as dual pathways for synaptic conductance, and voltage-dependent Mg²⁺ blockade. These features make the model pertinent for studies concerning synaptic transmission, neuronal integration, and plasticity mechanisms like long-term potentiation and depression. Notably, NMDA receptor dynamics are crucial for understanding complex information processing in neural networks and how neurons modify their connections in response to activity (a basis for learning and memory).