
The human entorhinal cortex exhibits a distinct set of synaptic features that differentiate this region from other human cortical areas, with a predominantly homogeneous synaptic organization across layers, except for layers I and VI.


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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 Statement Analysis 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.

### Competing Interest Statement

The authors have declared no competing interest.

*   3D
    :   three-dimensional
    AS
    :   asymmetric synapses
    CA1
    :   Cornu Ammonis 1
    CA2
    :   Cornu Ammonis 2
    CA3
    :   Cornu Ammonis 3
    CF
    :   counting frame
    CSR
    :   complete spatial randomness
    DG
    :   dentate gyrus
    EC
    :   entorhinal cortex
    HF
    :   hippocampal fissure
    FIB/SEM
    :   focused ion beam/scanning electron microscopy
    KS
    :   Kolmogorov-Smirnov
    LEC
    :   lateral entorhinal cortex
    MEC
    :   medial entorhinal cortex
    MW
    :   Mann-Whitney
    PaS
    :   parasubiculum
    PB
    :   phosphate buffer
    PRC
    :   perirhinal cortex
    PHC
    :   parahippocampal cortex
    PrS
    :   presubiculum
    PSD
    :   postsynaptic density
    S
    :   Subiculum
    SAS
    :   synaptic apposition surface
    SD
    :   standard deviation
    SE
    :   standard error of the mean
    SEM
    :   scanning electron microscopy
    SS
    :   symmetric synapses
    Vv
    :   volume fraction
    TEM
    :   transmission electron microscopy.

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

comprehensive-ultrastructural-analysis-of-synaptic-organization-in-the-human-entorhinal-cortex


Comprehensive Ultrastructural Analysis of Synaptic Organization in the Human Entorhinal Cortex
