AMPA receptor

One of three types of ionotropic glutamate receptor, along with NMDA receptors and kainate receptors. It is commonly co-located with NMDA receptors in the post-synaptic membrane.

AMPA receptors act faster than NMDA receptors: a 1ms 'pulse' of increased glutamate concentration almost instantly leads to about 1ms of current flow through the AMPA receptor (but this then shuts off, even if the glutamate concentration is sustained), whereas the response at an NMDA receptor takes ~20ms to ramp up and lasts ~100ms, long after the glutamate release has finished.

When bound to glutamate, the AMPA receptor ion channel opens to allow sodium and potassium ions into the cell. If the glutamate signal is strong enough, these ions will depolarize the synaptic membrane enough to unblock the NMDA receptor channels (which are ordinarily blocked by magnesium ions). So AMPA receptors are not just faster than NMDA receptors, but are actually a prerequisite.

In a predictive processing model of the brain, there is some evidence suggesting that NMDA receptor signaling tends to carry top-down predictions, while AMPA receptor signaling tends to carry bottom-up sensory information (prediction errors):

In a hierarchical cortical system in which representations become more abstract with increasing distance from the primary input, higher levels of the hierarchy specify top-down predictions through NMDA receptor signaling and any mismatches between expectancy and experience are conveyed upward through the hierarchy via rapid AMPA and GABA signaling.

There is some neurophysiological support for this contention; however, it is unlikely that NMDA receptors only signal predictions and AMPA receptors signal prediction errors; rather, there may be a division of labor where AMPA receptors are relatively more engaged bottom-up and NMDA receptors are relatively more involved in top-down processes.

References:

• https://smoothbrains.net/posts/2023-08-01-ketamine.html