This study investigates the structural basis of long-term potentiation (LTP) in single dendritic spines of hippocampal CA1 pyramidal neurons. Using two-photon photolysis of caged glutamate, the researchers found that repetitive quantum-like photorelease of glutamate induces rapid and selective enlargement of stimulated spines, which is transient in large mushroom spines but persistent in small spines. The spine enlargement is associated with an increase in AMPA-receptor-mediated currents and is dependent on NMDA receptors, calmodulin, and actin polymerization. Long-lasting spine enlargement also requires Ca/calmodulin-dependent protein kinase II. The results suggest that individual spines follow Hebb's postulate for learning, with small spines being preferential sites for LTP induction, while large spines may represent physical traces of long-term memory. The study provides insights into the structural and functional plasticity of dendritic spines and their role in synaptic potentiation and memory formation.This study investigates the structural basis of long-term potentiation (LTP) in single dendritic spines of hippocampal CA1 pyramidal neurons. Using two-photon photolysis of caged glutamate, the researchers found that repetitive quantum-like photorelease of glutamate induces rapid and selective enlargement of stimulated spines, which is transient in large mushroom spines but persistent in small spines. The spine enlargement is associated with an increase in AMPA-receptor-mediated currents and is dependent on NMDA receptors, calmodulin, and actin polymerization. Long-lasting spine enlargement also requires Ca/calmodulin-dependent protein kinase II. The results suggest that individual spines follow Hebb's postulate for learning, with small spines being preferential sites for LTP induction, while large spines may represent physical traces of long-term memory. The study provides insights into the structural and functional plasticity of dendritic spines and their role in synaptic potentiation and memory formation.