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 layer III of the anterior cingulate cortex (Brodmann area 24) and the temporopolar cortex, including the temporal pole (Brodmann area 38 ventral and dorsal) and anterior middle temporal gyrus (Brodmann area 21). Our results, based on 6695 synaptic junctions fully reconstructed in 3D, revealed that Brodmann 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.

We would like to thank Carmen Álvarez and Lorena Valdés for their technical assistance, and Nick Guthrie for his excellent text editing. Competing interestThe authors declare that they have no competing interest FundingThis study was funded by grants from the following entities: Spanish "Ministerio de Ciencia e Innovación" grant PGC2018-094307-B-I00; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain, CB06/05/0066); the Alzheimer's Association (ZEN-15-321663); the European Union's Horizon 2020 Framework Programme for Research and Innovation under grant agreement No. 945539 (Human Brain Project SGA3). LB-L gained a postdoctoral contract from the UNED (Plan de Promoción de la Investigación, 2014-040-UNED-POST), MM-C was awarded a research fellowship from the Spanish "Ministerio de Educación y Formación Profesional" (FPU14/02245), NC-A was awarded a research fellowship from the Spanish "Ministerio de Ciencia e Innovación" (PRE2019-089228) and SP-A was awarded a research fellowship from the Spanish "Ministerio de Ciencia e Innovación" (FPU19/00007).