Why does the NMDA receptor need glycine as well as glutamate? · Grey Matter

The NMDA receptor is built from GluN1 subunits, which bind glycine (or D-serine), and GluN2 subunits, which bind glutamate, and the channel opens only when both sites are occupied.

Why does the NMDA receptor need glycine as well as glutamate?

The NMDA receptor is built from GluN1 subunits, which bind glycine (or D-serine), and GluN2 subunits, which bind glutamate, and the channel opens only when both sites are occupied. Johnson and Ascher showed in 1987 that glycine at low concentrations strongly increases NMDA responses, and later work found it to be required. The co-agonist site is a second key: glutamate signals the synapse's activity, and the level of glycine or D-serine, partly set by glial transporters and release, adjusts how readily NMDA receptors in a region can open. This glycine site is separate from the glycine receptor that inhibits spinal neurons, and it is insensitive to strychnine.