Exploiting volume electron microscopy to investigate structural plasticity and stability of the postsynaptic compartment of central synapses

Volume reconstruction from electron microscopy datasets is a tool increasingly used to study the ultrastructure of the synapse in the broader context of neuronal network and brain organization. Fine modifications of synapse structure, such as activity-dependent dendritic spine enlargement and changes in the size and shape of the postsynaptic density, occur upon maturation and plasticity. The lack of structural plasticity or the inability to stabilize potentiated synapses are associated with synaptic and neuronal functional impairment. Mapping these rearrangements with the high resolution of electron microscopy proved to be essential in order to establish precise correlations between the geometry of synapses and their functional states. In this review we discuss recent discoveries on the substructure of the postsynaptic compartment of central excitatory synapses and how those are correlated with functional states of the neuronal network. The added value of volume electron microscopy analyses with respect to conventional transmission electron microscopy studies is highlighted considering that some limitations of volume-based methods imposed several adjustments to describe the geometry of this synaptic compartment and new parameters–that are good indicators of synapses strength and activity–have been introduced.