# Biological Basis of the Glutamate Synaptic Current Model The provided model code simulates glutamatergic synaptic currents, focusing specifically on the synaptic activation caused by AMPA and NMDA receptors, which are critical for excitatory transmission in the central nervous system. ## Key Biological Components Modeled ### AMPA and NMDA Receptors - **AMPA Receptors (AMPARs):** These are ionotropic receptors mediating fast synaptic transmission. In the code, AMPARs are described using an alpha function model, characterized by a rapid rise time (tau1) and exponential decay. AMPARs are highly permeable to Na⁺ ions and contribute to the initial phase of excitatory postsynaptic potentials (EPSPs). - **NMDA Receptors (NMDARs):** These receptors are unique due to their voltage-dependent ion channel gating mechanisms and permeability to Ca²⁺ ions in addition to Na⁺. The model uses a bi-exponential function to simulate NMDAR dynamics, capturing the slow rise and decay times of NMDAR currents. The code also incorporates magnesium (Mg²⁺) block, a key feature of NMDARs that makes their activity dependent on the membrane voltage. This is modeled using the "mgblock" function, which factors in external Mg²⁺ concentration and membrane potential to determine the extent of the block. ### Voltage Dependency and Mg²⁺ Block NMDARs exhibit a Mg²⁺ block that is relieved upon depolarization. This voltage-dependence is crucial for synaptic plasticity processes, such as long-term potentiation (LTP). The model adopts the Mg²⁺ blocking mechanism from the Jahr & Stevens equation, reflecting the physical blockage of the channel in a voltage-dependent manner. ### Short-term Synaptic Plasticity - **Facilitation:** The model includes a facilitation mechanism, where the probability of neurotransmitter release increases after an action potential (AP). This is modeled by an increment factor (Af) impacting the release probability (Pr) and its decay over time (tauF). - **Depression:** A depletion of readily releasable pool (RRP) of vesicles following an AP leads to synaptic depression. This is captured by reducing available vesicles based on factors such as utilization of synaptic resources, depressed by the product of release probability and facilitation. ### Synaptic Parameters - **Conductance Ratios:** The model specifies an NMDA/AMPA ratio (ntar) to balance the contribution of each receptor type to the synaptic current. - **Kinetic Parameters:** Parameters such as rise (tau2) and decay (tau3) times for NMDARs and tau1 for AMPARs are set to capture the temporal aspects of synaptic current responses. ### External and Resting Conditions - **Resting Membrane Potential:** The reversal potential is set to 0 mV, typical for excitatory postsynaptic current calculations. - **External Mg²⁺ Concentration:** The concentration of Mg²⁺ in the extracellular space significantly influences NMDAR activity. In summary, this model simulates the electrochemical and kinetic properties of AMPA and NMDA receptor-mediated synaptic currents, considering key factors such as synaptic plasticity, receptor kinetics, and voltage-dependent ion channel gating to reflect the physiological behavior of glutamatergic synapses.