The article by Christian Lüscher and Robert C. Malenka provides an in-depth review of NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are forms of synaptic plasticity that can be induced by activating NMDA-type glutamate receptors, typically through the coincident activity of pre- and postsynaptic neurons. The early phases of LTP and LTD are mediated by the redistribution of AMPA-type glutamate receptors, with more receptors being added to potentiate the synapse or removed to weaken it. Over time, structural changes become apparent, often requiring the synthesis of new proteins. The authors discuss the molecular and cellular mechanisms underlying these forms of synaptic plasticity, which have attracted significant attention due to their potential role in learning and memory. They focus on the induction, expression, and maintenance of LTP and LTD, highlighting the importance of calcium influx through NMDARs and the subsequent activation of signaling cascades such as CaMKII. The article also explores the involvement of protein synthesis in maintaining the changes in synaptic strength and the structural modifications that occur during LTP and LTD. Additionally, the authors discuss the broader implications of altered LTP and LTD in various brain diseases, including Alzheimer's disease and addiction. They emphasize the need for further research to understand the detailed molecular mechanisms underlying these forms of synaptic plasticity and their role in disease pathophysiology.The article by Christian Lüscher and Robert C. Malenka provides an in-depth review of NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are forms of synaptic plasticity that can be induced by activating NMDA-type glutamate receptors, typically through the coincident activity of pre- and postsynaptic neurons. The early phases of LTP and LTD are mediated by the redistribution of AMPA-type glutamate receptors, with more receptors being added to potentiate the synapse or removed to weaken it. Over time, structural changes become apparent, often requiring the synthesis of new proteins. The authors discuss the molecular and cellular mechanisms underlying these forms of synaptic plasticity, which have attracted significant attention due to their potential role in learning and memory. They focus on the induction, expression, and maintenance of LTP and LTD, highlighting the importance of calcium influx through NMDARs and the subsequent activation of signaling cascades such as CaMKII. The article also explores the involvement of protein synthesis in maintaining the changes in synaptic strength and the structural modifications that occur during LTP and LTD. Additionally, the authors discuss the broader implications of altered LTP and LTD in various brain diseases, including Alzheimer's disease and addiction. They emphasize the need for further research to understand the detailed molecular mechanisms underlying these forms of synaptic plasticity and their role in disease pathophysiology.