Synaptic transmission is incredibly fast. For example at the neuromuscular junction, the minimum time between the appearance of the electrical activity in the axon terminal and the appearance of electrical activity in the muscle as little as .4-.5 ms.

How is this managed?

One of the ways is that the vesicles that contain neurotransmitters are docked very close to the membrane. I talked about this is an earlier article where reconstruction of electron micrographs showed that synaptic vesicles are hemifused to the membrane.

Here is another article in this vein. Siksou et al. in the Journal of Neuroscience performed elaborate 3D reconstruction of electron micrographs from the presynapse. These 3D reconstructions show that synaptic vesicles are tethered in little daisy chains to the membrane by filaments of protein.

Photos of this are below the fold (warning these are big files).

The following is from Figure 3 of the paper. The caption reads:

Figure 3. Filaments linking the SVs to the presynaptic membrane. A-E, Example of virtual sections through the same bouton. A, B, Low-power view with SVs either docked (arrow) or at distance (crossed arrow). Filaments interconnect SVs together (white arrowhead) or with the plasma membrane (black arrowhead). Note the short strands (white arrow) between a docked vesicle (black arrow) and the presynaptic membrane. C-E, Sequence of virtual sections (one of six serial sections) establishing the continuity of a filament (arrowheads) linking a vesicle (crossed arrow) to the presynaptic membrane. F-H, Example of a filament contacting several SVs in virtual sections through another bouton. Five SVs are in contact with a filament (arrowheads). I, 3D reconstruction of the filaments (pink) and the adjacent SVs. The SVs numbered in I are those in F-H. Scale bars: A, B, 200 nm; C-H, 100 nm.

Here is the figure (click to enlarge):

Figure 3 shows how they make these 3D reconstructions. They methodically go section by section following the tiny filaments that tether to the vesicles to the membrane.

Below is from Figure 4 of the paper. It shows what the presynapse looks like when they bring these images together. The white part is the axon terminal. The yellow are tethered vesicles. Blue is docked vesicles. The pink is filaments. The dark blue is the post-synaptic density.

The researchers indicate in their discussion that on average a synaptic vesicle is tethered to about 1.5 other vesicles and that the length of the bridging filaments is about 30 nm.

I don't have much to say about this paper other than we now know that there are at least two ways that the synapse guarantees that neurotransmitters are released quickly: hemifusion and vesicle tethering.

I just think it is really cool that they can get pictures with such great resolution.