ADF/cofilin: a crucial regulator of synapse physiology and behavior

Actin filaments (F-actin) are the major structural component of excitatory synapses, being present in presynaptic terminals and in postsynaptic dendritic spines. In the last decade, it has been appreciated that actin dynamics, the assembly and disassembly of F-actin, is crucial not only for the structure of excitatory synapses, but also for pre- and postsynaptic physiology. Hence, regulators of actin dynamics take a central role in mediating neurotransmitter release, synaptic plasticity, and ultimately behavior. Actin depolymerizing proteins of the ADF/cofilin family are essential regulators of actin dynamics, and a number of recent studies highlighted their crucial functions in excitatory synapses. In dendritic spines, ADF/cofilin activity is required for spine enlargement during initial long-term potentiation (LTP), but needs to be switched off during spine stabilization and LTP consolidation. Conversely, active ADF/cofilin is needed for spine pruning during long-term depression (LTD). Moreover, ADF/cofilin controls activity-induced synaptic availability of glutamate receptors, and exocytosis of synaptic vesicles. These data show that the activity of ADF/cofilin in synapses needs to be spatially and temporally tightly controlled through several upstream regulatory pathways, which have been identified recently. Hence, ADF/cofilin-controlled actin dynamics emerged as a critical and central regulator of synapse physiology. In this review, I will summarize and discuss our current knowledge on the roles of ADF/cofilin in synapse physiology and behavior, by focusing on excitatory synapses of the mammalian central nervous system.