Long-Term Potentiation / Depression (LTP/LTD)
Activity-dependent strengthening or weakening of synaptic connections.
Overview
LTP is a persistent increase in synaptic strength following high-frequency stimulation. NMDA receptor activation by coincident pre- and postsynaptic activity allows Ca²⁺ influx, activating CaMKII. CaMKII phosphorylates AMPA receptors and promotes their insertion into the postsynaptic membrane. Late-phase LTP requires CREB-mediated gene transcription and protein synthesis. LTD involves lower Ca²⁺ levels activating calcineurin and protein phosphatases, leading to AMPA receptor internalization.
Cellular Location
Hippocampal and cortical synapses
Clinical Significance
Cellular basis of learning and memory; impaired in Alzheimer's disease; enhanced understanding informs nootropic development; synaptic tagging explains input-specific plasticity.