Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics.
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.
Rust
Marco B
MB
Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo, Italy.
Gurniak
Christine B
CB
Renner
Marianne
M
Vara
Hugo
H
Morando
Laura
L
Görlich
Andreas
A
Sassoè-Pognetto
Marco
M
Banchaabouchi
Mumna Al
MA
Giustetto
Maurizio
M
Triller
Antoine
A
Choquet
Daniel
D
Witke
Walter
W
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D051338:Cofilin 1 / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology; D007858:Learning; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D051338:Cofilin 1; D008840:Microfilament Proteins; D018091:Receptors, AMPA
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