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 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 (FIB/SEM) to perform a three-dimensional 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 disease. Significance Statement The present study represents the first attempt to unveil the detailed synaptic organization of the neuropil of the human entorhinal cortex — a brain region that is essential for memory function and spatial navigation. Using 3D electron microscopy, we have characterized the synaptic morphology and identified the postsynaptic targets of thousands of synapses. The results provide a new, large, quantitative ultrastructure dataset of the synaptic organization of the human entorhinal cortex. These data provide critical information to better understand synaptic functionality in the human brain. Highlight Estimation of the number of synapses, as well as determination of their type, shapes, sizes and postsynaptic targets, provides critical data to better understand synaptic functionality. This study provides a new, large, quantitative ultrastructure dataset of the synaptic organization of the human entorhinal cortex using 3D electron microscopy.