PT - JOURNAL ARTICLE AU - Lydia Maus AU - Bekir Altas AU - JeongSeop Rhee AU - Nils Brose AU - Cordelia Imig AU - Benjamin H. Cooper TI - Correlating Synaptic Ultrastructure and Function at the Nanoscale AID - 10.1101/588848 DP - 2019 Jan 01 TA - bioRxiv PG - 588848 4099 - http://biorxiv.org/content/early/2019/03/26/588848.short 4100 - http://biorxiv.org/content/early/2019/03/26/588848.full AB - Despite similarities in the composition of the molecular release machinery, synapses can exhibit strikingly different functional transmitter release properties and short- and long-term plasticity characteristics. To address the question whether ultrastructural differences could contribute to this functional synaptic heterogeneity, we employed a combination of hippocampal organotypic slice cultures, high-pressure freezing, freeze substitution, and 3D-electron tomography to resolve the spatial organization of vesicle pools at individual active zones (AZ) in two functionally distinct synapses, namely Schaffer collateral (SC) and mossy fiber (MF) synapses. We found that mature MF and SC synapses harbor equal numbers of docked vesicles at their AZs, MF synapses at rest exhibit a second pool of possibly ‘tethered’ vesicles in the AZ vicinity, and MF synapses contain at least three morphological types of docked vesicles, indicating that differences in the ultrastructural organization of MF and SC synapses may contribute to their respective functional properties and corresponding plasticity characteristics.