Long-term potentiation (LTP) is believed to be the mechanism through which memories are formed. Playing an integral part are the AMPA and NMDA receptors. They are ionotropic receptors, which control sodium and calcium gradients. At the cellular level, they help mediate synaptic responses enhanced during LTP; additionally, the NMDA receptor is necessary to initiate LTP. Donald Hebb believed that structural changes in synapses were the result of activation of a loop of neurons. These changes lead to functionally connected synapses. This is essentially what LTP does and this intuitive mechanism was postulated without any evidence showing that these theoretical structures even existed. Bliss and Lomo (1973) reported mammalian synapses capable of changes that Hebb had hypothesized years before. At that point, scientists knew they were closer to understanding memory.
Stimulation of these pathways or loops has been shown to produce synaptic responses. Low-frequency stimulation of perforant path axons of hippocampal cells in rats elicits relatively stable depolarization and synaptic response in postsynaptic neurons on the dentate gyrus . Furthermore, repeated high-frequency stimulation of perforant path axons leads to other structural changes. Subsequent stimulation leads to higher magnitude postsynaptic responses. This increased efficacy could last between an hour to several weeks.