ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity

Abstract

Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity, in which the actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins are important. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology but can also enhance synaptic potentiation in some cases. Thus, ADF/cofilin may have distinct effects on postsynaptic structure and function. We found that ADF/cofilin-mediated actin dynamics regulated AMPA receptor (AMPAR) trafficking during synaptic potentiation, which was distinct from actin's structural role in spine morphology. Specifically, elevated ADF/cofilin activity markedly enhanced surface addition of AMPARs after chemically induced long-term potentiation (LTP), whereas inhibition of ADF/cofilin abolished AMPAR addition. We found that chemically induced LTP elicited a temporal sequence of ADF/cofilin dephosphorylation and phosphorylation that underlies AMPAR trafficking and spine enlargement. These findings suggest that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity. © 2010 Nature America, Inc. All rights reserved.