How can the same NMDA receptor make a synapse stronger or weaker? · Grey Matter

Both directions start with calcium entering a spine through NMDA receptors, and the pattern of that calcium decides which way the synapse goes.

How can the same NMDA receptor make a synapse stronger or weaker?

Both directions start with calcium entering a spine through NMDA receptors, and the pattern of that calcium decides which way the synapse goes. A large, fast rise, produced by strong coincident activity such as a high-frequency burst, activates kinases (above all CaMKII) that add and strengthen AMPA receptors, which is LTP. A modest, prolonged rise, produced by low-frequency activity such as 900 pulses at 1 Hz, favours phosphatases that dephosphorylate AMPA receptors and pull them out of the membrane, which is LTD. NMDA receptor blockers prevent both, which is how Dudek and Bear showed in 1992 that this form of LTD needs the same receptor as LTP.