Ash's grade

Long-term potentiation (LTP) is a persistent strengthening of synaptic transmission triggered by high-frequency stimulation of a synapse. The NMDA receptor acts as a 'coincidence detector': it only opens when two conditions are simultaneously met — glutamate binds to it AND the postsynaptic membrane is sufficiently depolarized (which displaces the Mg²⁺ ion that normally blocks the channel at rest). When both conditions are met, Ca²⁺ flows into the postsynaptic neuron through the NMDA receptor, activating kinases like CaMKII, which phosphorylate existing AMPA receptors (increasing their conductance) and trigger the insertion of additional AMPA receptors into the synapse — this is the early, rapid phase of LTP. For late-phase LTP (lasting hours to days), gene expression and protein synthesis are required, leading to structural changes such as dendritic spine enlargement and even the formation of new synaptic contacts, making the potentiation anatomically durable. AMPA receptors thus serve as the primary mediators of the strengthened response, while NMDA receptors serve as the induction gate that initiates the entire cascade.