Three-Dimensional Synaptic Organization of Layer III of the Human Temporal Neocortex

Most data are available in the main text or the Supplementary Materials. The datasets used and analyzed during the current study are published in the EBRAINS Knowledge Graph (DOI: 10.25493/5F04-N97): Domínguez-Álvaro M, Montero M, Alonso-Nanclares L, Blazquez-Llorca L, Rodríguez J-R, DeFelipe J. (2020). Densities and 3D distributions of synapses using FIB/SEM imaging in the human neocortex (Temporal cortex, T2) [Data set]. Human Brain Project Neuroinformatics Platform.In the present study, we have used Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to perform a study of the synaptic organization of layer III of Brodmann’s area 21 in human tissue samples obtained from autopsies and biopsies. We analyzed the synaptic density, 3D spatial distribution, and type (asymmetric/symmetric), as well as the size and shape of each synaptic junction of 4945 synapses that were fully reconstructed in 3D. Significant differences in the mean synaptic density between autopsy and biopsy samples were found (0.49 and 0.66 synapses/μm3 , respectively). However, in both types of samples (autopsy and biopsy), the asymmetric:symmetric ratio was similar (93:7) and most asymmetric synapses were established on dendritic spines (75%), while most symmetric synapses were established on dendritic shafts (85%). We also compared several electron microscopy methods and analysis tools to estimate the synaptic density in the same brain tissue. We have shown that FIB/SEM is much more reliable and robust than the majority of the other commonly used EM techniques. The present work constitutes a detailed description of the synaptic organization of cortical layer III. Further studies on the rest of the cortical layers are necessary to better understand the functional organization of this temporal cortical region.This study was funded by grants from the following entities: Spanish “Ministerio de Ciencia e Innovación” grant PGC2018-094307-B-I00, and the Cajal Blue Brain Project made available under aCC-BY-NC 4.0 International license. (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is bioRxiv preprint doi: https://doi.org/10.1101/2021.01.18.427131; this version posted April 8, 2021. The copyright holder for this preprint 59 (the Spanish partner of the Blue Brain Project initiative from EPFL [Switzerland]); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain, CB06/05/0066); and the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreement No. 945539 (Human Brain Project SGA3). N C-A was awarded a research fellowship from the Spanish “Ministerio de Ciencia e Innovación” (PRE2019-089228).Peer reviewe