biostudies-literatureUnknownGlausier JRNIEHS NIH HHSNIMH NIH HHSNIAAA NIH HHSSynaptic function is directly reflected in quantifiable ultrastructural features using electron microscopy (EM) approaches. This coupling of synaptic function and ultrastructure suggests that <i>in vivo</i> synaptic function can be inferred from EM analysis of <i>ex vivo</i> human brain tissue. To investigate this, we employed focused ion beam-scanning electron microscopy (FIB-SEM), a volume EM (VEM) approach, to generate ultrafine-resolution, three-dimensional (3D) micrographic datasets of postmortem human dorsolateral prefrontal cortex (DLPFC), a region with cytoarchitectonic characteristics distinct to human brain. Synaptic, sub-synaptic, and organelle measures were highly consistent with findings from experimental models that are free from antemortem or postmortem effects. Further, 3D neuropil reconstruction revealed a unique, ultrastructurally-complex, spiny dendritic shaft that exhibited features characteristic of heightened synaptic communication, integration, and plasticity. Altogether, our findings provide critical proof-of-concept data demonstrating that <i>ex vivo</i> VEM analysis is an effective approach to infer <i>in vivo</i> synaptic functioning in human brain.bioRxiv : the preprint server for biology2024.02.26.582174https://www.ebi.ac.uk/biostudies/studies/S-EPMC10925168biostudies-literatureVolume electron microscopy reveals 3D synaptic nanoarchitecture in postmortem human prefrontal cortex.PMC10925168R21 AA028800R01 ES034037S10 MH133575R01 MH132544Banks-Tibbs TWu KGlausier JRMaier MFreyberg ZMelchitzky DBouchet-Marquis CNing JLewis DAfalseVolume electron microscopy reveals 3D synaptic nanoarchitecture in postmortem human prefrontal cortex.Synaptic function is directly reflected in quantifiable ultrastructural features using electron microscopy (EM) approaches. This coupling of synaptic function and ultrastructure suggests that <i>in vivo</i> synaptic function can be inferred from EM analysis of <i>ex vivo</i> human brain tissue. To investigate this, we employed focused ion beam-scanning electron microscopy (FIB-SEM), a volume EM (VEM) approach, to generate ultrafine-resolution, three-dimensional (3D) micrographic datasets of postmortem human dorsolateral prefrontal cortex (DLPFC), a region with cytoarchitectonic characteristics distinct to human brain. Synaptic, sub-synaptic, and organelle measures were highly consistent with findings from experimental models that are free from antemortem or postmortem effects. Further, 3D neuropil reconstruction revealed a unique, ultrastructurally-complex, spiny dendritic shaft that exhibited features characteristic of heightened synaptic communication, integration, and plasticity. Altogether, our findings provide critical proof-of-concept data demonstrating that <i>ex vivo</i> VEM analysis is an effective approach to infer <i>in vivo</i> synaptic functioning in human brain.2024-01-01T00:00:00Z2024 Sep2026-04-08T19:54:38.342Z2026-04-08T14:34:24.247ZS-EPMC109251683846398610.1101/2024.02.26.582174