3D Ultrastructural Study of Synapses in the Human Entorhinal Cortex

The entorhinal cortex (EC) is a brain region that has been shown to be essential for memory functions and spatial navigation. However, detailed three-dimensional (3D) synaptic morphology analysis and identification of postsynaptic targets at the ultrastructural level have not been performed before in the human EC. In the present study, we used Focused Ion Beam/Scanning Electron Microscopy to perform a 3D analysis of the synapses in the neuropil of medial EC in layers II and III from human brain autopsies. Specifically, we studied synaptic structural parameters of 3561 synapses, which were fully reconstructed in 3D. We analyzed the synaptic density, 3D spatial distribution, and type (excitatory and inhibitory), as well as the shape and size of each synaptic junction. Moreover, the postsynaptic targets of synapses could be clearly determined. The present work constitutes a detailed description of the synaptic organization of the human EC, which is a necessary step to better understand the functional organization of this region in both health and diseaseSpanish “Ministerio de Ciencia e Innovación” (grant PGC2018-094307-B-I00); the Cajal Blue Brain Project (the Spanish partner of the Blue Brain Project initiative from EPFL, [Switzerland]); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain (CB06/05/0066); the Alzheimer’s Association (ZEN-15-321663); the European Union’s Horizon 2020 Framework Programme for Research and Innovation (grant agreement No. 945539) to Human Brain Project SGA3; the Spanish “Ministerio de Educación y Formación Profesional” (FPU14/02245 to M.M.-C.); UNED (Plan de Promoción de la Investigación, 2014-040-UNED-POST to L.B.-L.) We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).