- coincidence detector requiring Glutamate, a co-agonist (Glycine or D-serine), and postsynaptic depolarization to relieve the Mg²⁺ block
- depolarization usually comes from AMPA Receptors, but can also come from backpropagating action potentials or local dendritic activity
- conducts Na⁺ and Ca²⁺ inward, K⁺ outward; Ca²⁺ links electrical activity to intracellular plasticity signaling
- in many synapses, NMDA helps trigger Long Term Potentiation and Long Term Depression, while changes in AMPA Receptor number and conductance express the altered synaptic strength
- not a clean NMDA = Hebbian / AMPA = homeostatic split becuase AMPA participates in both
- conventional receptors have two GluN1 and two GluN2 subunits; subunit compositon changes kinetics, pharmacology, and how inputs are integrated over time
- slower currents than AMPA Receptors extend the window for integrating nearby inputs
- important for many forms of learning-related plasticity and local circuit changes, but not the universal mechanism behind all LTP, LTD, or memory
- NMDA is a synthetic agonist used to define the receptor class; Glutamate is the endogenous agonist
- inhibitors act through different mechanisms
- Mg²⁺ produces voltage-dependent pore block; Zn²⁺ inhibition depends on subunit composition
- D-AP5 competes at the glutamate-binding site; Ketamine and Memantine are open-channel blockers