Chapter 8 - The NMDA Receptor

Abstract

The properties of the N-methyl-D-aspartate (NMDA) receptor that allow to function in unique role of selectively triggering long-term synaptic potentiation, and indeed memory, are important. This chapter discusses regulation of the NMDA receptor. There are three major categories of molecular components and processes that are involved in NMDA receptor regulation. First are the molecular mechanisms upstream of the NMDA receptor that directly regulate its function, processes like phosphorylation, redox regulation, and modulatory ligand binding. These processes can serve to integrate signals over a longer time span than the relatively short-lived glutamate binding and membrane depolarization. Second are the mechanisms upstream of the NMDA receptor that control membrane depolarization. These mechanisms localized in the postsynaptic cell serve to fine-tune and regulate the depolarization envelope that the NMDA receptor senses. Third are the components of the synaptic infrastructure that control its function. The NMDA receptor is embedded in the postsynaptic density, a rich milieu of molecules many of which are able to directly or indirectly affect NMDA receptor function. In addition, many components of the postsynaptic density serve as targets of the NMDA receptor in terms of its triggering downstream molecular consequences. They are functional categories to help organize the complex biochemical machinery of NMDA receptor regulation, not compartmentalized biochemical processes in the cell.