Enhanced cycling of presynaptic vesicles during long-term potentiation in rat hippocampus.

Long-term potentiation (LTP) is a widely studied form of synaptic plasticity engaged during learning and memory. Here the ultrastructural evidence is reviewed that supports an elevated and sustained increase in the probability of vesicle release and recycling during LTP. In hippocampal area CA1, small dense-core vesicles and tethered synaptic vesicles are recruited to presynaptic boutons enlarging active zones. By 2 h during LTP, there is a sustained loss of vesicles, especially in presynaptic boutons containing mitochondria and clathrin-coated pits. This decrease in vesicles accompanies an enlargement of the presynaptic bouton, suggesting they supply membrane needed for the enlarged bouton surface area. The spatial relationship of vesicles to the active zone varies with functional status. Tightly docked vesicles contact the presynaptic membrane and are primed for release of neurotransmitter upon the next action potential. Loosely docked vesicles are located within 8 nm of the presynaptic membrane. Non-docked vesicles comprise recycling and reserve pools. Vesicles are tethered to the active zone via filaments composed of molecules engaged in docking and release processes. Electron tomography reveals clustering of docked vesicles at higher local densities in active zones after LTP. Furthermore, the tethering filaments on vesicles at the active zone are shorter, and their attachment sites are shifted closer to the active zone. These changes suggest more vesicles are docked, primed and ready for release. The findings provide strong ultrastructural evidence for a long-lasting increase in release probability following LTP.