Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics

• Published in: The EMBO journal Vol. 29; no. 11; pp. 1889 - 1902
• Main Authors: Rust, Marco B, Gurniak, Christine B, Renner, Marianne, Vara, Hugo, Morando, Laura, Görlich, Andreas, Sassoè-Pognetto, Marco, Banchaabouchi, Mumna Al, Giustetto, Maurizio, Triller, Antoine, Choquet, Daniel, Witke, Walter
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 02.06.2010; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: actin cytoskeleton; Actin Depolymerizing Factors - metabolism; Actins - metabolism; Actins - physiology; Animals; Binding sites; Carrier Proteins - metabolism; Cell Membrane - metabolism; Cofilin 1 - metabolism; Cytoskeleton - metabolism; Dendritic Spines - metabolism; Dendritic Spines - physiology; EMBO05; EMBO27; Learning; Long-Term Potentiation - physiology; Memory; Mice; Mice, Transgenic; Microfilament Proteins - metabolism; Molecular biology; Neurology; neuronal physiology; Neuronal Plasticity - physiology; Neurons; Physiology; Proteins; Receptors, AMPA - metabolism; Spine; synaptic plasticity; actin cytoskeleton; neuronal physiology; synaptic plasticity
• DOI: 10.1038/emboj.2010.72
• ISSN: 0261-4189

Neuronal plasticity is an important process for learning, memory and complex behaviour. Rapid remodelling of the actin cytoskeleton in the postsynaptic compartment is thought to have an important function for synaptic plasticity. However, the actin‐binding proteins involved and the molecular mechanisms that in vivo link actin dynamics to postsynaptic physiology are not well understood. Here, we show that the actin filament depolymerizing protein n‐cofilin is controlling dendritic spine morphology and postsynaptic parameters such as late long‐term potentiation and long‐term depression. Loss of n‐cofilin‐mediated synaptic actin dynamics in the forebrain specifically leads to impairment of all types of associative learning, whereas exploratory learning is not affected. We provide evidence for a novel function of n‐cofilin function in synaptic plasticity and in the control of extrasynaptic excitatory AMPA receptors diffusion. These results suggest a critical function of actin dynamics in associative learning and postsynaptic receptor availability.