Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity.
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.
Okamoto
Ken-Ichi
K
RIKEN-MIT Neuroscience Research Center, The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nagai
Takeharu
T
Miyawaki
Atsushi
A
Hayashi
Yasunori
Y
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D031541:Fluorescence Resonance Energy Transfer; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D019044:Image Cytometry; D051379:Mice; D041681:NIH 3T3 Cells; D009473:Neuronal Plasticity / Q000502:physiology*; D017711:Nonlinear Dynamics; D009924:Organ Culture Techniques; D011485:Protein Binding; D051381:Rats; D013570:Synaptic Membranes / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D000199:Actins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases