Volume Electron Microscopy Analysis of Synapses in Associative and Primary Regions of the Human Cerebral Cortex

Abstract Functional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored due to the difficulties involved in studying the human brain at the nanoscopic level. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous synaptic datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics appeared to be specific to particular cortical regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. These observations may be included within the general rules of synaptic organization of the human cerebral cortex. The present results on nanoscopic characteristics of synapses provide further insights into the structural design of the human cerebral cortex. Significance statement Structural and functional studies investigating macroscopic connectivity in the human cerebral cortex have suggested that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. Here, thousands of synaptic junctions were 3D reconstructed in associative and primary cortical regions. We found that certain synaptic characteristics appeared to be specific to particular cortical regions —regardless of whether they are associative or primary cortex— whereas others were common to all analyzed regions. The present results provide further insights into the structural design of the human cerebral cortex.