toplogo
Sign In

Comprehensive Ultrastructural Analysis of Synaptic Organization in the Human Entorhinal Cortex


Core Concepts
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.
Abstract
The study used volume electron microscopy to perform a detailed 3D analysis of the synapses in all layers of the human medial entorhinal cortex (MEC). The key findings are: No significant differences in synaptic density were found between layers, with an average of 0.41 synapses/μm3. The majority of synapses were excitatory (asymmetric, AS) with a similar AS:symmetric (SS) ratio across layers. Most synapses fitted a random spatial distribution pattern, though some layers showed tendencies towards clustered or regular distributions. AS synapses were larger than SS synapses. The size of AS synapses was relatively uniform across layers, except for smaller sizes in layer VI and larger sizes in layers III and Va/b. The majority of synapses had a macular shape, with complex-shaped synapses (perforated, horseshoe, fragmented) being larger. Layer VI had the lowest proportion of macular synapses. Around 60% of synapses were established on dendritic spines, predominantly on spine heads. AS synapses preferred dendritic spines, while SS synapses preferred dendritic shafts. These findings provide a comprehensive ultrastructural dataset on the synaptic organization of the human entorhinal cortex, which is crucial for understanding the connectivity and function of this brain region in both health and disease.
Stats
The mean synaptic density across all layers was 0.41 synapses/μm3. The proportion of asymmetric (excitatory) to symmetric (inhibitory) synapses was 96:4 on average. The mean area of asymmetric synaptic junctions was 118,492 nm2, while for symmetric synapses it was 70,051 nm2. 60% of synapses were established on dendritic spines, with 59.3% being asymmetric synapses on spine heads.
Quotes
"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." "Our findings show remarkable uniformity in the synaptic characteristics. This may seem surprising given the cytoarchitectonic and innervation complexity of the medial entorhinal cortex." "The data presented here aim to represent a step towards a better understanding of the networks and connectivity characteristics of the human cerebral cortex."

Deeper Inquiries

How do the synaptic features of the entorhinal cortex compare to other brain regions involved in memory and spatial navigation, such as the hippocampus?

The synaptic features of the entorhinal cortex (EC) exhibit some similarities and differences compared to other brain regions involved in memory and spatial navigation, like the hippocampus. In terms of synaptic density, the EC showed values similar to other cortical regions but slightly lower than the hippocampus. The AS:SS ratio in the EC was consistent with that of other cortical regions, indicating a higher proportion of excitatory synapses. Additionally, the distribution of synapses in the EC appeared to be random, a common pattern observed in various brain regions. One notable difference is the layer-specific variations in synaptic size and shape observed in the EC. While AS synapses were larger than SS synapses across all layers, there were differences in the size of synapses among the layers of the EC. This layer-specific variation in synaptic size and shape may reflect unique functional characteristics of each layer within the EC. Furthermore, the preference of AS for dendritic spines and SS for dendritic shafts in the EC is consistent with the general synaptic organization observed in other brain regions involved in memory and spatial navigation. This specific targeting of postsynaptic elements may play a crucial role in the information processing and connectivity within the EC, similar to the hippocampus.

How do the potential functional implications of the layer-specific differences in synaptic size and shape observed in the entorhinal cortex?

The layer-specific differences in synaptic size and shape observed in the entorhinal cortex (EC) may have significant functional implications for information processing and connectivity within this brain region. The variations in synaptic size among the layers could reflect differences in synaptic strength, efficacy, and plasticity. Larger synapses are associated with a higher release probability and synaptic strength, potentially leading to more robust and stable synaptic connections. The prevalence of complex-shaped synapses in certain layers of the EC, such as layer VI, may indicate a specific connectivity pattern characterized by synapses with higher synaptic strengths. These larger and more complex synapses could play a crucial role in long-lasting memory-related functionality and information processing within the EC. Furthermore, the layer-specific distribution of synapses on dendritic spines and shafts suggests a targeted and specialized connectivity within the EC. The preference of excitatory synapses for dendritic spines and inhibitory synapses for dendritic shafts may contribute to the precise regulation of neural activity and information flow within the EC, supporting memory and spatial navigation functions.

Could the synaptic organization of the entorhinal cortex be altered in neurodegenerative diseases like Alzheimer's, and how might this contribute to the early pathological changes observed in this region?

The synaptic organization of the entorhinal cortex (EC) could be altered in neurodegenerative diseases like Alzheimer's, particularly considering the early pathological changes observed in this region. In Alzheimer's disease, there is a progressive loss of synapses and neuronal connectivity, leading to cognitive decline and memory impairment. The EC is one of the first regions affected by Alzheimer's disease, showing significant synaptic and neuronal loss in the early stages of the disease. The alterations in synaptic organization in the EC in Alzheimer's disease may include changes in synaptic density, synaptic size, and shape, as well as disruptions in the balance between excitatory and inhibitory synapses. These alterations could contribute to the early pathological changes observed in the EC, such as the accumulation of amyloid plaques and neurofibrillary tangles, which are hallmark features of Alzheimer's disease. Furthermore, the disruption of synaptic connectivity within the EC could impact the flow of information between the hippocampus and neocortex, leading to deficits in memory function and spatial navigation. The loss of synapses and alterations in synaptic organization in the EC may disrupt the neural circuits involved in memory processes, contributing to the cognitive decline seen in Alzheimer's disease.
0