Three small vesicular pools in sequence govern synaptic response dynamics during action potential trains

During prolonged trains of presynaptic action potentials (APs), synaptic release reaches a stable level that reflects the speed of replenishment of the readily releasable pool (RRP). Determining the size and filling dynamics of vesicular pools upstream of the RRP has been hampered by a lack of precision of synaptic output measurements during trains. Using the recent technique of tracking vesicular release in single active zone synapses, we now developed a method that allows the sizes of the RRP and upstream pools to be followed in time. We find that the RRP is fed by a small-sized pool containing approximately one to four vesicles per docking site at rest. This upstream pool is significantly depleted by short AP trains, and reaches a steady, depleted state for trains of >10 APs. We conclude that a small, highly dynamic vesicular pool upstream of the RRP potently controls synaptic strength during sustained stimulation.

Automated summary

During the transmission of presynaptic action potentials, there is a small vesicular pool that replenishes the readily releasable pool of synapses. This vesicular pool is significantly depleted by short bursts of action potentials and reaches a steady state when stimulated by more than 10 action potentials. The control of this vesicular pool plays a crucial role in synaptic strength.