The dendritic spine vicinome: characterizing its crowding in the human brain with petavoxel electron microscopy
For more than a century we have pictured the dendritic spine as the postsynaptic point where a single presynaptic bouton delivers its message. That picture is correct but incomplete, since it overlooks other neuronal elements surrounding each spine. Here we characterize that neighborhood for the first time by counting and measuring the proximity of the elements encircling each postsynaptic spine.…
For over a century, scientists have depicted the dendritic spine as the sole point of communication between a presynaptic bouton and the postsynaptic neuron. However, this picture is only partial, as it disregards the other elements that coexist around each spine. In a groundbreaking study, researchers have now characterized this surrounding neighborhood, which they have dubbed the vicinome. The vicinome encompasses the complete array of neuronal and glial components that encircle a dendritic spine.
To achieve this, the scientists utilized meticulously crafted three-dimensional meshes from the H01 petavoxel dataset, a comprehensive reconstruction of the human cerebral cortex. From this dataset, they analyzed 4,550 neighboring elements surrounding 322 spines in 17 pyramidal neurons, distributed across cortical layers 2 to 5. Each spine was classified as either apical or basal.
The study revealed a depth gradient in the number of neighboring elements, with layer 2 apical spines hosting 17.2 ± 4.2 elements per spine, while layer 5 basal spines had fewer neighbors at 12.5 ± 3.1. A linear mixed model with random intercepts per neuron confirmed a significant effect of layer (p = 4.3 x 10-5) on the number of neighbors, with large effect sizes (Cohen's d up to 1.45). Notably, the polarity of the spine showed no significant impact on neighbor number.
The minimum distance between spines and their nearest neighbors remained consistent, approximately 30 nanometers, across all groups. Although some depth-related contrasts were observed, their effect sizes remained insignificant (Cohen's d below 0.21). The researchers concluded that cortical depth, rather than the polarity of the pyramidal neuron, was the key factor influencing the number of neuronal elements neighboring the spine.
This study suggests that the vicinome could serve as a valuable measurable observable for comparisons across various regions, ages, species, and disease states. By understanding the crowding of elements within the vicinome, researchers may gain new insights into the complex organization of the human brain and its potential implications for neurological disorders.
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