Regulation of actin dynamics in dendritic spines: Nanostructure, molecular mobility, and signaling mechanisms.

Dendritic spines are major sites of excitatory synaptic connection in pyramidal neurons of the forebrain, and their functional regulation underlies the development of functional neuronal circuits and experience-dependent circuit plasticity. Dendritic spines contain a large amount of actin filaments, and their organization and dynamics control both the morphology and function of dendritic spines. New optical technologies, including super-resolution microscopy, fluorescence lifetime imaging, and fluorescence correlation measurements, have helped gather further information about the nanoscale features of spine structure and cytoskeletal organization, together with the molecular interactions and mobility within spines. These experiments identified signals that are responsible for actin reorganization in nascent spine formation, the dynamic regulation of actin assembly/disassembly in spine nanodomains, and the interaction between actin and other cytoskeletal and membranous components that modulate synaptic functions. We discuss the crucial roles of nanoscale actin dynamics in both nascent and mature spines, which may differ fundamentally in the organization of actin filaments. Combined with the progress in the mathematical simulation of spine actin dynamics, realistic modeling of spine nanostructure based on the dynamic organization of actin filaments will become possible. The models will promote our understanding of the complex interaction between the structure, function, and signaling of dendritic spines.