Single-spine functions studied with two-photon photolysis of caged-glutamate

Haruo Kasai

Abstract

Dendritic spines of pyramidal neurons in the cerebral cortex undergo an activity-dependent structural remodeling that has been proposed to be a cellular basis of learning and memory. It has remained unknown, however, how structural remodeling supports synaptic plasticity, such as long-term potentiation (LTP), and whether such plasticity is input specific at the level of the individual spine. We have now investigated the structural basis of LTP with the use of two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons8. Repetitive quantum-like uncaging of glutamate induced a rapid and selective enlargement of stimulated spines that was transient in large mushroom spines but persistent in small spines. Spine enlargement was associated with an increase in AMPA receptor-mediated currents at the stimulated synapse and was dependent on NMDA receptors, calmodulin, and actin polymerization. Long-lasting spine enlargement also required 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 LTP induction, while large spines might represent physical traces of long-term memory.

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Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N., Nakahara, H. (2003). Structure-stability-function relationships of dendritic spines. Trends in Neurosciences 26, 360-368.

Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R. & Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature in press. PDF

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