NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD) are forms of synaptic plasticity that occur when NMDA-type glutamate receptors are activated by the simultaneous activity of pre- and postsynaptic neurons. These processes are essential for learning and memory. LTP involves the strengthening of synapses, while LTD involves their weakening. The early phases of LTP and LTD are mediated by the redistribution of AMPA-type glutamate receptors, with more receptors added or removed to alter synaptic strength. Over time, structural changes occur, requiring new protein synthesis. AMPARs and NMDARs are ionotropic glutamate receptors that are permeable to Na+ and K+. AMPARs are calcium-impermeable when they contain GluA2, while NMDARs are permeable to calcium but only when the postsynaptic neuron is depolarized. The current-voltage relationship of these receptors varies, with AMPARs showing linear or inward-rectifying behavior depending on the presence of GluA2. LTP and LTD are induced by specific patterns of neuronal activity. LTP requires simultaneous activation of pre- and postsynaptic neurons, leading to calcium influx through NMDARs and subsequent signaling cascades that alter synaptic strength. LTD can be induced by low-frequency activation of the presynaptic neuron without postsynaptic activity. The expression of LTP and LTD involves the insertion or removal of AMPARs into or from the postsynaptic membrane, which is regulated by proteins such as stargazin and PICK1. The induction of LTP and LTD is linked to the timing of presynaptic and postsynaptic activity, with spike-timing-dependent plasticity being a key mechanism. The expression of LTP and LTD involves the redistribution of AMPARs, which is regulated by SNARE-mediated exocytosis and dynamin-dependent endocytosis. These processes are influenced by signaling cascades involving CaMKII, protein kinases, and phosphatases. LTP and LTD are maintained by protein synthesis, with local dendritic translation and nuclear transcription playing key roles. Structural changes in synapses, such as spine enlargement or shrinkage, are associated with LTP and LTD, respectively. These changes are linked to the stabilization or removal of synaptic inputs. Altered LTP and LTD have been implicated in various brain diseases, including Alzheimer's disease and addiction. In Alzheimer's, soluble Aβ oligomers disrupt LTP and LTD mechanisms, leading to synaptic dysfunction. In addiction, drugs like cocaine alter synaptic transmission and plasticity, leading to long-lasting changes in excitatory synapses. Understanding the molecular and cellular mechanisms underlying LTP and LTD is crucial for elucidating the mechanisms of learning and memory, as well as for developing treatments for neurological disorders.NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD) are forms of synaptic plasticity that occur when NMDA-type glutamate receptors are activated by the simultaneous activity of pre- and postsynaptic neurons. These processes are essential for learning and memory. LTP involves the strengthening of synapses, while LTD involves their weakening. The early phases of LTP and LTD are mediated by the redistribution of AMPA-type glutamate receptors, with more receptors added or removed to alter synaptic strength. Over time, structural changes occur, requiring new protein synthesis. AMPARs and NMDARs are ionotropic glutamate receptors that are permeable to Na+ and K+. AMPARs are calcium-impermeable when they contain GluA2, while NMDARs are permeable to calcium but only when the postsynaptic neuron is depolarized. The current-voltage relationship of these receptors varies, with AMPARs showing linear or inward-rectifying behavior depending on the presence of GluA2. LTP and LTD are induced by specific patterns of neuronal activity. LTP requires simultaneous activation of pre- and postsynaptic neurons, leading to calcium influx through NMDARs and subsequent signaling cascades that alter synaptic strength. LTD can be induced by low-frequency activation of the presynaptic neuron without postsynaptic activity. The expression of LTP and LTD involves the insertion or removal of AMPARs into or from the postsynaptic membrane, which is regulated by proteins such as stargazin and PICK1. The induction of LTP and LTD is linked to the timing of presynaptic and postsynaptic activity, with spike-timing-dependent plasticity being a key mechanism. The expression of LTP and LTD involves the redistribution of AMPARs, which is regulated by SNARE-mediated exocytosis and dynamin-dependent endocytosis. These processes are influenced by signaling cascades involving CaMKII, protein kinases, and phosphatases. LTP and LTD are maintained by protein synthesis, with local dendritic translation and nuclear transcription playing key roles. Structural changes in synapses, such as spine enlargement or shrinkage, are associated with LTP and LTD, respectively. These changes are linked to the stabilization or removal of synaptic inputs. Altered LTP and LTD have been implicated in various brain diseases, including Alzheimer's disease and addiction. In Alzheimer's, soluble Aβ oligomers disrupt LTP and LTD mechanisms, leading to synaptic dysfunction. In addiction, drugs like cocaine alter synaptic transmission and plasticity, leading to long-lasting changes in excitatory synapses. Understanding the molecular and cellular mechanisms underlying LTP and LTD is crucial for elucidating the mechanisms of learning and memory, as well as for developing treatments for neurological disorders.