Long-term potentiation (LTP) is a persistent increase in synaptic strength following high-frequency stimulation of a synapse. First described by Bliss and Lomo (1973) in the hippocampus, LTP has the properties expected of a memory mechanism: it is activity-dependent, input-specific, associative, and long-lasting (hours to weeks or longer). It is widely considered the primary cellular mechanism underlying learning and memory.
Mechanisms
LTP at glutamatergic synapses (the most common form) requires activation of NMDA receptors, which serve as coincidence detectors: they open only when the postsynaptic membrane is already depolarized (indicating the neuron has recently been active) and glutamate is bound (indicating the presynaptic neuron has fired). This coincidence detection implements the Hebbian principle: "neurons that fire together, wire together." The resulting calcium influx triggers signaling cascades that increase the number and efficacy of AMPA receptors at the synapse.
The link between LTP and memory is supported by multiple lines of evidence: drugs that block LTP impair learning, genetic manipulations that enhance LTP improve memory in mice, and the induction of LTP at specific synapses can create artificial memories. The discovery of place cells, grid cells, and sharp-wave ripples in the hippocampus has provided increasingly detailed models of how LTP-like synaptic changes encode specific memories during experience and consolidate them during sleep.