Network bursts in hippocampal microcultures are terminated by exhaustion of vesicle pools

Synchronized network activity is an essential attribute of the brain. Yet the cellular mechanisms that determine the duration of network bursts are not fully understood. In the present study, synchronized network bursts were evoked by triggering an action potential in a single neuron in otherwise silent microcultures consisting of 4-30 hippocampal neurons. The evoked burst duration, ∼2 s, depended on the recovery time after a previous burst. While interburst intervals of 35 s enabled full-length bursts, they were shortened by half at 5-s intervals. This reduction in burst duration could not be attributed to postsynaptic parameters such as glutamate receptor desensitization, accumulating afterhyperpolarization, inhibitory tone, or sodium channel inactivation. Reducing extracellular Ca(2+) concentration ([Ca(2+)](o)) relieved the effect of short intervals on burst duration, while depletion of synaptic vesicles with α-latrotoxin gradually eliminated network bursts. Finally, a transient exposure to high [K(+)](o) slowed down the recovery time following a burst discharge. We conclude that the limiting factor regulating burst duration is most likely the depletion of presynaptic resources.