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 show that repetitive glutamate uncaging induces rapid and selective enlargement of stimulated spines. Small spines show persistent enlargement, while large spines exhibit transient changes. Spine enlargement is associated with increased AMPA receptor-mediated currents and depends on NMDA receptors, calmodulin, and actin polymerization. Long-lasting enlargement also requires Ca/calmodulin-dependent protein kinase II, indicating that spines individually follow Hebb's postulate for learning. Small spines are preferential sites for LTP induction, while large spines may represent physical traces of long-term memory. The study also shows that spine enlargement is closely related to the pharmacology, amplitude, time course, and spatial localization of synaptic potentiation. Spine enlargement occurs rapidly, similar to LTP, and is dependent on actin polymerization. The expression of AMPA receptors in spines is dependent on F-actin and scaffolding proteins. Spine enlargement, which is also dependent on actin polymerization, may promote the accumulation of AMPA receptors. However, the precise molecular mechanisms of F-actin reorganization and AMPA receptor expression remain to be clarified. The study demonstrates that both structural and functional plasticity can be induced at the level of the individual spine. The results indicate that a Hebbian mechanism can operate individually in single spines of hippocampal CA1 pyramidal neurons. Small spines are preferential sites for LTP induction, which may correspond to the postsynaptic structures of silent synapses. Large spines, which express AMPA receptors abundantly and are stable for months in the mouse cerebral cortex, may represent physical traces of long-term memory. The memory stored in large spines might be protected from further potentiation caused by its readout and new memory formation. Further clarification of the structural bases of synaptic potentiation and depression should give greater insight into the operation of memory units in the brain.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 show that repetitive glutamate uncaging induces rapid and selective enlargement of stimulated spines. Small spines show persistent enlargement, while large spines exhibit transient changes. Spine enlargement is associated with increased AMPA receptor-mediated currents and depends on NMDA receptors, calmodulin, and actin polymerization. Long-lasting enlargement also requires Ca/calmodulin-dependent protein kinase II, indicating that spines individually follow Hebb's postulate for learning. Small spines are preferential sites for LTP induction, while large spines may represent physical traces of long-term memory. The study also shows that spine enlargement is closely related to the pharmacology, amplitude, time course, and spatial localization of synaptic potentiation. Spine enlargement occurs rapidly, similar to LTP, and is dependent on actin polymerization. The expression of AMPA receptors in spines is dependent on F-actin and scaffolding proteins. Spine enlargement, which is also dependent on actin polymerization, may promote the accumulation of AMPA receptors. However, the precise molecular mechanisms of F-actin reorganization and AMPA receptor expression remain to be clarified. The study demonstrates that both structural and functional plasticity can be induced at the level of the individual spine. The results indicate that a Hebbian mechanism can operate individually in single spines of hippocampal CA1 pyramidal neurons. Small spines are preferential sites for LTP induction, which may correspond to the postsynaptic structures of silent synapses. Large spines, which express AMPA receptors abundantly and are stable for months in the mouse cerebral cortex, may represent physical traces of long-term memory. The memory stored in large spines might be protected from further potentiation caused by its readout and new memory formation. Further clarification of the structural bases of synaptic potentiation and depression should give greater insight into the operation of memory units in the brain.