Memory  >   NMDA Receptors Control Memory Processes

The NMDA Receptor

An NMDA receptor (NMDAR) consists of two GluN1 (formerly NR1) subunits and two additional subunits which are predominately either GluN2A (NR2A) or GluN2B (NR2B). Other subunits, GluN3, GluN2C and GluN2D, are relatively rare. The activation of NMDAR requires two events: binding of glutamate and relief of Mg2+ block. NMDARs are localized to the postsynaptic membrane. At the resting membrane potential, NMDARs are blocked by Mg2+ ions. If the membrane potential is sufficiently depolarized, the outward depolarizing field may repel Mg2+ out of the pore. On the other hand, binding of glutamate can open the intrinsic gate of NMDARs (via unknown mechanisms).


Figure 4-1. Schematic drawing of the NMDAR, whose activation requires the glutamate binding to open an intrinsic gate, and the membrane depolarizing field to relieve Mg2+ block. In this example, the NMDAR contains the GluN2B subunit, which plays a much more important role than GluN2A in memory processes.

Crucial Enzymes for Memory Processes

The opening of NMDAR allows Ca2+ ions to enter the neuron. Inside a cell, many enzymes are known to be under the regulation of Ca2+ ions, either directly or indirectly. Regarding memory, three enzymes are most relevant: Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA) and protein phosphatase 2B (also known as calcineurin). A protein kinase catalyzes the phosphorylation reaction, which adds a negatively charged phosphate group PO43- to a protein. A phosphatase catalyzes the reverse reaction, i.e., removing a phosphate group from a protein. The three enzymes play crucial roles in long-term potentiation (LTP), long-term depression (LTD), memory extinction and memory retrieval.


Author: Frank Lee
First Published: January, 2018