Vesicle number does not predict postsynaptic measures of miniature synaptic activity frequency in cultured cortical neurons.

We tested the hypothesis that heterogeneity in the frequency of miniature synaptic activity reflects differences in the number of vesicles present in presynaptic terminals. Using imaging techniques, we measured dendritic miniature synaptic calcium transients attributed to the spontaneous release of single transmitter quanta. Following imaging, the identified neurons were processed for serial transmission electron microscopy. At sites of quantal Ca(2+) transients mediated by N-methyl-D-aspartate receptors, we confirmed the presence of excitatory synapses and measured the total number of vesicles and the number of docked vesicles. We observed no correlation between the frequency of spontaneous miniature activity and either the total vesicle number or the number of docked vesicles. We conclude that the presynaptic vesicle complement as measured by ultrastructural analysis does not necessarily determine the frequency of spontaneous activity at synapses mediated by N-methyl-D-aspartate receptors.