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1 Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.; Center for NanoBio Integration, University of Tokyo, Tokyo 113-0033, Japan.; Department of Cell Physiology, National Institute for Physiological Sciences, and Graduate University of Advanced Studies (SOKENDAI), Myodaiji, Okazaki 444-8787, Japan. 2 Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.; Center for NanoBio Integration, University of Tokyo, Tokyo 113-0033, Japan. 3 Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.; Center for NanoBio Integration, University of Tokyo, Tokyo 113-0033, Japan.; Department of Cell Physiology, National Institute for Physiological Sciences, and Graduate University of Advanced Studies (SOKENDAI), Myodaiji, Okazaki 444-8787, Japan.; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, Japan. 4 Department of Pharmacology and Physiology, Drexel University College of Medicine,
Philadelphia, Pennsylvania 19102, USA.
* To whom correspondence should be addressed.
Haruo Kasai , E-mail: hkasai{at}m.u-tokyo.ac.jp
These authors contributed equally to this work.
Long-term potentiation (LTP) at glutamatergic synapses is consideredto underlie learning and memory, and is associated with enlargementof dendritic spines. Because consolidation of memory and LTPrequires protein synthesis, it is important to clarify how proteinsynthesis affects spine enlargement. Repetitive pairing of postsynapticspikes and two-photon uncaging of glutamate at single spines(spike-timing protocol) displayed both immediate and gradualphases of spine enlargement in CA1 pyramidal neurons. The gradualenlargement was strongly dependent on protein-synthesis andBDNF action, often associated with spine twitching, and wasinduced specifically at the spines which were immediately enlargedby the synaptic stimulation. Thus, spike-timing protocol isan efficient trigger for BDNF secretion, and induces protein-synthesisdependent longterm enlargement at the level of single spines.
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