Letters to Nature
Nature 429, 761-766 (17 June 2004) | doi:10.1038/nature02617; Received 18 December 2003; Accepted 10 May 2004; Published online 9 June 2004
Structural basis of long-term potentiation in single dendritic spines
Masanori Matsuzaki1, Naoki Honkura1, Graham C. R. Ellis-Davies2 & Haruo Kasai1
- Department of Cell Physiology, National Institute for Physiological Sciences and The Graduate University of Advanced Studies (Sokendai), Myodaiji, Okazaki 444-8787, Japan
- Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA
Correspondence to: Haruo Kasai1 Correspondence and requests for materials should be addressed to H.K. (Email: hkasai@nips.ac.jp).
Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling1, 2, 3, 4, 5 that has been proposed to be a cellular basis of learning and memory6. How structural remodelling supports synaptic plasticity4, 5, such as long-term potentiation7, 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 neurons8. 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.
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