Abstract
The synapse is a highly organized cellular specialization whose structure and composition are reorganized, both positively and negatively, depending on the strength of input signals. The mechanisms orchestrating these changes are not well understood. A plausible locus for the reorganization of synapse components and structure is actin, because it serves as both cytoskeleton and scaffold for synapses and exists in a dynamic equilibrium between F-actin and G-actin that is modulated bidirectionally by cellular signaling. Using a new FRET-based imaging technique to monitor F-actin/G-actin equilibrium, we show here that tetanic stimulation causes a rapid, persistent shift of actin equilibrium toward F-actin in the dendritic spines of rat hippocampal neurons. This enlarges the spines and increases postsynaptic binding capacity. In contrast, prolonged low-frequency stimulation shifts the equilibrium toward G-actin, resulting in a loss of postsynaptic actin and of structure. This bidirectional regulation of actin is actively involved in protein assembly and disassembly and provides a substrate for bidirectional synaptic plasticity.
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Acknowledgements
We thank K. Takao, H. Fujisawa, T. Kiuchi, E. Ruthazer, R. Malinow, M. Sheng, J. Lisman, F. Gertler, T. Emery and E. Hueske for valuable advice and sharing of resources. Y.H. is supported in part by The Ellison Medical Foundation.
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Okamoto, KI., Nagai, T., Miyawaki, A. et al. Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci 7, 1104–1112 (2004). https://doi.org/10.1038/nn1311
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DOI: https://doi.org/10.1038/nn1311