Rapid Ultrastructural Changes of PSD and Extrasynaptic Axon-spine Interface Membrane during LTP Induced in Single Dendritic Spine

Structural plasticity of dendritic spines is considered to be the basis of synaptic plasticity, learning and memory. Here, we performed ultrastructural analysis of spines undergoing LTP using a novel high throughput correlative light-electron microscopy approach. We found that the PSD displays rapid (< 3 min) reorganization of its nanostructure, including perforation and segmentation. This increased structural complexity is maintained over intermediate and late phases of LTP (20 and 120 min). In a few spines, segmented PSDs are connected to different presynaptic terminals, producing a multi-innervated spine in the intermediate and late phases. In addition, the area of extrasynaptic axon-spine interface (eASI) displayed a pronounced, rapid and sustained increase. Finally, presynaptic vesicle number increased slowly and became significantly higher at late phases of LTP. These rapid ultrastructural changes in PSD and surrounding membrane, together with the slow increase in presynaptic vesicle number, likely support the rapid and sustained increase in synaptic transmission during LTP.