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Science 319 (5870): 1683-1687

Copyright © 2008 by the American Association for the Advancement of Science

Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines

Jun-ichi Tanaka,1,2,3* Yoshihiro Horiike,1,2* Masanori Matsuzaki,1,2,3,4 Takashi Miyazaki,1,2,3 Graham C. R. Ellis-Davies,5 Haruo Kasai1,2,3{dagger}

Abstract: Long-term potentiation (LTP) at glutamatergic synapses is considered to underlie learning and memory and is associated with the enlargement of dendritic spines. Because the consolidation of memory and LTP require protein synthesis, it is important to clarify how protein synthesis affects spine enlargement. In rat brain slices, the repetitive pairing of postsynaptic spikes and two-photon uncaging of glutamate at single spines (a spike-timing protocol) produced both immediate and gradual phases of spine enlargement in CA1 pyramidal neurons. The gradual enlargement was strongly dependent on protein synthesis and brain-derived neurotrophic factor (BDNF) action, often associated with spine twitching, and was induced specifically at the spines that were immediately enlarged by the synaptic stimulation. Thus, this spike-timing protocol is an efficient trigger for BDNF secretion and induces protein synthesis–dependent long-term enlargement at the level of single spines.

1 Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
2 Center for NanoBio Integration, University of Tokyo, Tokyo 113-0033, Japan.
3 Department of Cell Physiology, National Institute for Physiological Sciences, and Graduate University of Advanced Studies (SOKENDAI), Myodaiji, Okazaki 444-8787, Japan.
4 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
5 Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: hkasai{at}m.u-tokyo.ac.jp

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