Structural basis of long-term potentiation in single dendritic spines.
Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.
Matsuzaki
Masanori
M
Department of Cell Physiology, National Institute for Physiological Sciences and The Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki 444-8787, Japan.
Honkura
Naoki
N
Ellis-Davies
Graham C R
GC
Kasai
Haruo
H
D000199:Actins / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D004553:Electric Conductivity; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D010782:Photolysis; D017785:Photons; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D000199:Actins; D002147:Calmodulin; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid