3D Synaptic Organization of Layer III of the Human Anterior Cingulate and Temporopolar Cortex

The human anterior cingulate and temporopolar cortices have been proposed as highly connected nodes involved in high-order cognitive functions, but their synaptic organization is still basically unknown due to the difficulties involved in studying the human brain. Using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to study the synaptic organization of the human brain obtained with a short post-mortem delay allows excellent results to be obtained. We have used this technology to analyze the neuropil (where the vast majority of synapses are found) of layer III of the anterior cingulate cortex (Brodmann’s area 24) and the temporopolar cortex, including the temporal pole (Brodmann’s area 38 ventral and dorsal) and anterior middle temporal gyrus (Brodmann’s area 21). Our results, based on 6695 synapses fully reconstructed in 3D, revealed that Brodmann’s areas 24, 21 and ventral area 38 showed similar synaptic density and synaptic size, whereas dorsal area 38 displayed the highest synaptic density and the smallest synaptic size. However, the proportion of the different types of synapses (excitatory and inhibitory), the postsynaptic targets and the shapes of excitatory and inhibitory synapses were similar, regardless of the region examined. These observations indicate that certain aspects of the synaptic organization are rather homogeneous, whereas others show specific variations across cortical regions. Since not all data obtained in a given cortical region can be extrapolated to other cortical regions, further studies on the other cortical regions and layers are necessary to better understand the functional organization of the human cerebral cortex. ### Competing Interest Statement The authors have declared no competing interest. * 3D : three-dimensional AMPA : α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AS : asymmetric synapses CA1 : Cornu Ammonis 1 CF : counting frame CSR : Complete Spatial Randomness FIB/SEM : focused ion beam/scanning electron microscopy KS : Kolmogorov-Smirnov MW : Mann-Whitney NMDA : N-methyl-D-aspartate PB : phosphate buffer PSD : postsynaptic density SAS : synaptic apposition surface SE : standard error of the mean SD : standard deviation SS : symmetric synapses Vv : volume fraction.