Synaptic plasticity is a cellular model for learning and memory. However, the expression mechanisms underlying presynaptic forms of plasticity are not well understood. Orlando et al. investigate functional and structural correlates of presynaptic potentiation at large hippocampal mossy fiber boutons induced by the adenylyl cyclase activator forskolin. The authors performed 2-photon imaging of the genetically encoded glutamate sensor iGluu that revealed an increase in the surface area used for glutamate release at potentiated terminals. By high-pressure freezing and transmission electron microscopy analysis, they found a rapid remodeling of synaptic ultrastructure at potentiated boutons: Synaptic vesicles dispersed in the terminal and accumulated at the active zones, while active zone density and synaptic complexity increased. The researchers suggest that these rapid and early structural rearrangements might enable long-term increase in synaptic strength. The image shows manual renderings of partial 3D reconstruction of hippocampal mossy fiber boutons in control conditions (left) or after forskolin treatment (right). The presynaptic membrane is green, and postsynaptic membrane is light blue. In the top images, synaptic vesicles are yellow, and active zones and docked or tethered vesicles are blue (control) or red (forskolin). In the bottom images, synaptic vesicles are blue (control) or red (forskolin).

Image Credit: pbio.3001149