Synaptic plasticity / LTP

Synaptic plasticity is the activity-dependent change in synaptic strength considered the cellular substrate of learning and memory. The cardinal form is long-term potentiation (LTP), first reported by Bliss and Lomo in 1973 in the dentate gyrus of the rabbit hippocampus after high-frequency stimulation of the perforant path. Hippocampal LTP is typically NMDA receptor dependent: postsynaptic depolarisation relieves the magnesium block of NMDA receptors, calcium entry activates CaMKII, and AMPA receptors are inserted at the postsynaptic density, increasing synaptic gain. Long-term depression, structural remodelling of dendritic spines and metaplasticity provide complementary mechanisms. NMDA receptor dependent LTP declines with age in rodents and is impaired by amyloid-beta oligomers, linking plasticity loss mechanistically to Alzheimer disease symptoms.