Journal
HIPPOCAMPUS
Volume 26, Issue 6, Pages 816-831Publisher
WILEY
DOI: 10.1002/hipo.22565
Keywords
actin cytoskeleton; AMPA receptor insertion; FRAP; neurite-growth inhibitors; structural plasticity
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Funding
- Deutsche Forschungsgemeinschaft [ZA 554/3-1]
- Advanced ERC Grant (NOGORISE) [294115]
- Swiss National Science Foundation [31-138676, 3100A0_12252711]
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Nogo-A and its receptors have been shown to control synaptic plasticity, including negatively regulating long-term potentiation (LTP) in the cortex and hippocampus at a fast time scale and restraining experience-dependent turnover of dendritic spines over days. However, the molecular mechanisms and the precise time course mediating these actions of Nogo-A are largely unexplored. Here we show that Nogo-A signaling in the adult nervous system rapidly modulates the spine actin cytoskeleton within minutes to control structural plasticity at dendritic spines of CA3 pyramidal neurons. Indeed, acute Nogo-A loss-of-function transiently increases F-actin stability and results in an increase in dendritic spine density and length. In addition, Nogo-A acutely restricts AMPAR insertion and mEPSC amplitude at hippocampal synaptic sites. These data indicate a crucial function of Nogo-A in modulating the very tight balance between plasticity and stability of the neuronal circuitry underlying learning processes and the ability to store long-term information in the mature CNS. (C) 2016 Wiley Periodicals, Inc.
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