Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy

Actin filaments are the major cytoskeletal elements of pre- and postsynaptic terminals.Actin exists in two states in the cell: as monomeric G-actin and as a two-stranded polar helical filament (F-actin) composed of G-actin. F-actin preferentially polymerizes at the barbed end of the filament and depolymerizes at the opposite, pointed end. A variety of actin-binding proteins influence the structure and organization of the actin cytoskeleton.By engaging actin regulatory proteins, synaptic activity can remodel both the pre- and the postsynaptic actin cytoskeleton.In the presynaptic terminal, actin is involved in maintaining and regulating synaptic vesicle pools, probably by serving as a scaffold to restrict vesicle mobility and by providing tracks to direct the transfer of vesicles between pools. At the active zone, actin can regulate vesicle docking and priming. Actin also facilitates the endocytic retrieval of synaptic vesicles.Recent findings show that actin dynamics are required for the sharing of synaptic vesicles between boutons along the axon, and that promoting actin polymerization is sufficient to unsilence presynaptic boutons in young neurons.At postsynaptic terminals, different pools of actin are specialized for the synaptic anchoring and exo–endocytic trafficking of neurotransmitter receptors.Most excitatory synapses are made onto dendritic spines that are enriched for F-actin. The size of dendritic spines positively correlates with the number of glutamate receptors at the postsynaptic density.Induction of synaptic plasticity changes the size and shape of spines, at least in part by reorganizing the underlying actin cytoskeleton. With LTP, spines become larger and increase their relative content of F-actin; with LTD, spines shrink and depolymerize their F-actin.The signalling pathways responsible for structural and functional synaptic plasticity diverge considerably, and conditions can be found for uncoupling the two processes. Under normal conditions, however, structural and functional modifications are interdependent and coordinated.Dysfunctions in synaptic actin dynamics have significant consequences for cognition and are closely associated with neurological disorders and dementia.