Digital Reconstruction of the Neuro-Glia-Vascular Architecture.

Eleftherios Zisis,Alexis Arnaudon,Thomas Delemontex,Pierre Julius Magistretti,Alessandro Foni,Felix Schürmann,Lida Kanari,Benoît Coste,Marwan Abdellah,Corrado Calì,Henry Markram,Michael Gevaert,Kathryn Hess,Daniel Keller

doi:10.1093/cercor/bhab254

Abstract

Astrocytes connect the vasculature to neurons mediating the supply of nutrients and biochemicals. They are involved in a growing number of physiological and pathophysiological processes that result from biophysical, physiological, and molecular interactions in this neuro-glia-vascular ensemble (NGV). The lack of a detailed cytoarchitecture severely restricts the understanding of how they support brain function. To address this problem, we used data from multiple sources to create a data-driven digital reconstruction of the NGV at micrometer anatomical resolution. We reconstructed 0.2 mm3 of the rat somatosensory cortex with 16 000 morphologically detailed neurons, 2500 protoplasmic astrocytes, and its microvasculature. The consistency of the reconstruction with a wide array of experimental measurements allows novel predictions of the NGV organization, allowing the anatomical reconstruction of overlapping astrocytic microdomains and the quantification of endfeet connecting each astrocyte to the vasculature, as well as the extent to which they cover the latter. Structural analysis showed that astrocytes optimize their positions to provide uniform vascular coverage for trophic support and signaling. However, this optimal organization rapidly declines as their density increases. The NGV digital reconstruction is a resource that will enable a better understanding of the anatomical principles and geometric constraints, which govern how astrocytes support brain function.

Highlights

Neurons, the principal subjects of neuroscience, are structurally and functionally linked to glia and the microvasculature, forming a complex system of multidirectional communication known as the neuro-glia-vascular (NGV; Fig. 1A) ensemble (Verkhratsky and Toescu 2006)
The neuro-glia-vascular ensemble (NGV) digital reconstruction is a resource that will enable a better understanding of the anatomical principles and geometric constraints, which govern how astrocytes support brain function
We provide a data resource that can be used to investigate the morphological intricacies of the NGV anatomical reconstruction, and which paves the route for the simulation of physiology throughout an entire brain region, embedded in its actual cortical space with a biologically realistic spatial architecture, and offers the possibility to shed light on unknown questions about the microscopic brain interactions

Summary

Introduction

The principal subjects of neuroscience, are structurally and functionally linked to glia and the microvasculature, forming a complex system of multidirectional communication known as the neuro-glia-vascular (NGV; Fig. 1A) ensemble (Verkhratsky and Toescu 2006). The most common type of glia, the protoplasmic astrocytes, radially extend between 5 and 10 primary processes (Damoiseaux and Greicius 2009; Di Benedetto et al 2016; Calì et al 2019; Moye et al 2019), which ramify progressively into finer and finer branches, filling up their entire spatial extent (Bushong et al 2002) Their fine leafletlike processes wrap around the axon–spine interface (Ventura and Harris 1999; Genoud et al 2006) forming tripartite units (Araque et al 1999; Santello et al 2012).

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