Although the correlation between synaptic structure and function has been studied in detail at the neuromuscular junction, we face many open questions. Central synapses are even less well understood. Recent studies have shown that the size of a single synaptic contact is correlated to its function. In particular the number of vesicles docked at the active zone seems to accurately predict the release probability of that contact. It is not clear, however, whether every vesicle contributes equally to the release probability. An exact mapping of the position of docked vesicles might reveal functional differences between individual vesicles. We, therefore, reconstructed hippocampal synapses by using high voltage electron microscopy and tomographic 3-D reconstructions. Using this method we can resolve the position of every vesicle with an error of less than 10 nm in all dimensions, whereas reconstructions from serial sections are limited to a 6 times lower resolution in the z-axis. Thus far, 10 synapses have been reconstructed. The center to center distances of the docked vesicles were calculated using the program xdsphere developed at NCMIR by Stephan Lamont and analyzed with the pair correlation function. The function shows a complex but orderly pattern that is consistent between active zones. This work was presented at the Winter Brain Conference this year in Park City, Utah.
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