Volume Electron Microscopy Reveals Unique Laminar Synaptic Characteristics in the Human Entorhinal Cortex

Abstract

The entorhinal cortex (EC) plays a pivotal role in memory function and spatial navigation, connecting the hippocampus with the neocortex. The EC integrates a wide range of cortical and subcortical inputs, but its synaptic organization in the human brain is largely unknown. We used volume electron microscopy to perform a 3D analysis of the synapses in all layers of the medial EC (MEC) from the human brain. Using this technology, 12,974 synapses were fully 3D reconstructed at the ultrastructural level. The MEC presented a distinct set of synaptic features, differentiating this region from other human cortical areas. Furthermore, synaptic organization within the MEC was predominantly homogeneous, although layers I and VI exhibited several synaptic characteristics that were distinct from other layers. The present study constitutes an extensive description of the synaptic organization of the neuropil of all layers of the EC, a crucial step to better understand the connectivity of this cortical region, in both health and disease.Significance StatementAnalysis of the synaptic characteristics provides crucial data on cortical organization. However, synaptic organization data for the normal human brain is virtually non-existent. The present study analyzes synaptic characteristics of the human entorhinal cortex at the ultrastructural level. This brain region is essential for memory processes and spatial navigation, acting as an interface between sensory areas and the hippocampus. Moreover, the entorhinal cortex is one of the first regions affected by Alzheimer’s disease. The present results provide a large quantitative ultrastructural dataset of synapses in all layers of the entorhinal cortex using 3D electron microscopy. Our findings show remarkable uniformity in the synaptic characteristics. This may seem surprising given the cytoarchitectonic and innervation complexity of the medial entorhinal cortex.