ADF/Cofilin-Mediated Actin Dynamics Regulate AMPA Receptor Trafficking during Synaptic Plasticity

Synapses of the vertebrate nervous system are highly plastic and undergo short- and long-term modifications during developmental refinement of the neural circuitry, as well as during learning and memory. Synaptic modulation can occur at the pre- and postsynaptic sides of the synapse. Presynaptically, synaptic strength can be modified by the altered probability of neurotransmitter release in response to each action potential. At the postsynaptic site, modification of the number, types and properties of surface neurotransmitter receptors is believed to give rise to bidirectional plasticity of the synapse 1–4 . Several ionotropic glutamate receptors are involved in excitatory synaptic transmission, of which AMPARs are best known for their rapid trafficking into and out of the synapse by cycling between intracellular stores and the cell surface during synaptic potentiation and depression, respectively 1–4 . Most of the excitatory synapses in the vertebrate brain reside on dendritic spines, tiny actin-based membrane protrusions that serve as the platform for postsynaptic specializations. Growth and shrinkage of dendritic spines have also been associated with long-term potentiation and depression (LTP and LTD), respectively 5–7 . It is generally thought that the morphological changes of postsynaptic spines are coupled to receptor trafficking during plasticity, which may function to dynamically adjust the membrane area for accommodating the changing number of synaptic receptors 8–10 . The actin cytoskeleton is important for postsynaptic structure, function and plasticity 10–12 . Actin is highly enriched in spines and