Mechanical regulation of synapse formation and plasticity

Dendritic spines are small protrusions arising from dendrites and constitute the major compartment of excitatory post-synapses. They change in number, shape, and size throughout life; these changes are thought to be associated with formation and reorganization of neuronal networks underlying learning and memory. As spines in the brain are surrounded by the microenvironment including neighboring cells and the extracellular matrix, their protrusion requires generation of force to push against these structures. In turn, neighboring cells receive force from protruding spines. Recent studies have identified BAR-domain proteins as being involved in membrane deformation to initiate spine formation. In addition, forces for dendritic filopodium extension and activity-induced spine expansion are generated through cooperation between actin polymerization and clutch coupling. On the other hand, force from expanding spines affects neurotransmitter release from presynaptic terminals. Here, we review recent advances in our understanding of the physical aspects of synapse formation and plasticity, mainly focusing on spine dynamics. [Display omitted] •BAR-domain proteins deform the dendritic membrane to initiate spine formation.•Actin polymerization and clutch coupling produce force to extend dendritic filopodia.•Cytoskeletons, CAMs, and the ECM provide mechanical support for spine structure.•Tunable clutch coupling mediates generation of force for spine structural plasticity.•Force from expanding spines affects presynaptic neurotransmitter release.