Synaptic vesicle recycling adapts to chronic changes in activity.

Synaptic vesicle recycling is essential for maintaining neurotransmission during rhythmic activity. To test whether the demands imposed by ambient activity influences synaptic vesicle trafficking, we compared the kinetics of synaptic depression in hippocampal versus neocortical cultures, which have high and low levels of intrinsic activity, respectively. In response to moderate 10 Hz stimulation, hippocampal synapses depressed less compared with neocortical synapses, although they reused vesicles more slowly. Therefore, during stimulation, hippocampal synapses used more vesicles from the reserve pool, whereas neocortical synapses relied on vesicle reuse. In hippocampal cultures, chronic block of network activity increased synaptic depression by decreasing the rate of vesicle mobilization, with little effect on the rate of vesicle reuse. In contrast, in neocortical cultures, an increase in the normally low network activity reduced synaptic depression by robustly increasing vesicle reuse with no effect on vesicle mobilization. These results suggest that synaptic vesicle trafficking and the resulting synaptic dynamics adapt to meet the changing demands on neurotransmitter release. Furthermore, during these functional modifications, synapses use alternate strategies to adjust to changes in activity.