NMDA Receptors, Multi-protein Complexes, & LTP

Professor Tom O'Dell describes the role played by NMDA receptors, as part of a large multi-protein complex, in facilitating long-term potentiation (LTP).

We think that crucial to detecting these different patterns of activity at the synapse – the patterns that will induce long-term potentiation or long-term depression – a key component of the machinery that detects those patterns is something called the NMDA (or N-methyl-D-aspartate) receptor for glutamate. But in addition, and coupled to, the NMDA receptor in this large multi-protein signaling complex is a whole host of signaling proteins and adaptor molecules and cytoskeletal proteins. We think what is happening (and much of this is still not well understood) is that these proteins, these signaling molecules, are being brought into this complex, so that they can produce a coordinated cellular response to activation of those NMDA-type receptors. In other words, when the synapse gets stronger there’s changes happening at the glutamate receptors that are at the synapse. There are also structural changes that are happening in the dendritic spines, in the dendritic trees of those cells. There are signals that are going down to the nucleus that cause changes in the gene expression. There are also signals that are regulating the excitability of the cell at many, many different places in the cell. This coordinated cellular response to a given input – activation of those NMDA receptors – is probably being coordinated by this large multi-protein complex, or signal receptor complex.