Cortical synapses have structural, molecular and functional
heterogeneity; our knowledge regarding the relationship between
their ultrastructural and functional parameters is still
fragmented. Here we asked how the neurotransmitter release
probability and presynaptic [Ca(2+)] transients relate to the
ultrastructure of rat hippocampal glutamatergic axon terminals.
Two-photon Ca(2+) imaging-derived optical quantal analysis and
correlated electron microscopic reconstructions revealed a tight
correlation between the release probability and the active-zone
area. Peak amplitude of [Ca(2+)] transients in single boutons
also positively correlated with the active-zone area. Freeze-
fracture immunogold labeling revealed that the voltage-gated
calcium channel subunit Cav2.1 and the presynaptic protein
Rim1/2 are confined to the active zone and their numbers scale
linearly with the active-zone area. Gold particles labeling
Cav2.1 were nonrandomly distributed in the active zones. Our
results demonstrate that the numbers of several active-zone
proteins, including presynaptic calcium channels, as well as
the number of docked vesicles and the release probability, scale
linearly with the active-zone area.
