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Structural basis of long-term potentiation in single dendritic spines


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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Figure 1: Spine-head enlargement induced by repetitive uncaging of MNI-glutamate.
Figure 2: Properties of the spine-head enlargement.
Figure 3: Colocalization of enlargement of spine heads and potentiation of AMPA-receptor-mediated currents.
Figure 4: Relationship between spine-head enlargement and potentiation of AMPA-receptor-mediated currents.

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We thank P. Haydon for reading the manuscript, N. Takahashi and T. Kise for technical assistance and Y. Yanagawa and M. Okabe for the eGFP construct. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (H.K. and M.M.) and by the Human Frontier Science Program Organization (G.C.R.E.-D. and H.K.), the NIH (G.C.R.E.-D. and H.K.), the NSF (G.C.R.E.-D) and the McKnight Endowment Fund for Neuroscience (G.C.R.E.-D).

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Correspondence to Haruo Kasai.

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Supplementary information

Supplementary Information

This contains additional figures (Supplementary Figures 1-3) and descriptions of spine-head enlargement. (DOC 532 kb)

Supplementary Methods

This file describes supplementary methods for estimation of spine-head volume. (DOC 21 kb)

Supplementary Movie 1

This movie shows enlargement of the spine head shown in Figure 1a. The stacked images were acquired every 3 to 16 min. The horizontal white bar shows time of image acquisition. Each marker represents 30 min. Repetitive uncaging of MNI-glutamate was affected when the white square appears. (MP4 209 kb)

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Matsuzaki, M., Honkura, N., Ellis-Davies, G. et al. Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761–766 (2004).

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