Counting Synaptic Vesicles: As Simple as That?

One critical parameter determining synaptic transmission and the modulation of long- and short-term synaptic plasticity is the size of the three functionally defined pools of synaptic vesicles (SVs) in particular that of the so-called readily releasable pool of SVs (RRP). However, due to the random distribution of SVs within a given synaptic bouton, it is impossible to describe a structural correlate to the functionally defined pools. Thus, the so-called “docked” SVs fused with the presynaptic density (PreAZ) or omega-shaped bodies already opened that released a quantum of neurotransmitter were regarded to represent the RRP. However, whether only “docked” or omega-shaped bodies represent the structural correlate of the RRP still remains controversially discussed. Here, we represent and compare two methods that can be used to describe the size of the RRP, a perimeter analysis where SVs are classified according to their distance to the PreAZ and high-resolution EM tomography by which the number of “docked” or omega-shaped SVs along the active zone are counted in individual tilt series along the PreAZ.