Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.; Brazhe, Alexey

doi:10.3389/fncel.2021.645068

“…The astrocytic arborization is relatively less explored. A recent study ( Verisokin et al, 2021 ) modeled the astrocyte morphology by forming Voronoi partitioning around randomly distributed seed points and matching the polygonal area patch from a given Voronoi partition to the closest astrocyte template extracted from experimental images of astrocytes. However, to the best of our knowledge, there are no published computational models that simulate the arborization of astrocyte processes.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model

Kumar

¹

,

Menon

²

,

Gayathri

³

et al. 2022

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Normal functioning of the brain relies on a continual and efficient delivery of energy by a vast network of cerebral blood vessels. The bidirectional coupling between neurons and blood vessels consists of vasodilatory energy demand signals from neurons to blood vessels, and the retrograde flow of energy substrates from the vessels to neurons, which fuel neural firing, growth and other housekeeping activities in the neurons. Recent works indicate that, in addition to the functional coupling observed in the adult brain, the interdependence between the neural and vascular networks begins at the embryonic stage, and continues into subsequent developmental stages. The proposed Vascular Arborization Model (VAM) captures the effect of neural cytoarchitecture and neural activity on vascular arborization. The VAM describes three important stages of vascular tree growth: (i) The prenatal growth phase, where the vascular arborization depends on the cytoarchitecture of neurons and non-neural cells, (ii) the post-natal growth phase during which the further arborization of the vasculature depends on neural activity in addition to neural cytoarchitecture, and (iii) the settling phase, where the fully grown vascular tree repositions its vascular branch points or nodes to ensure minimum path length and wire length. The vasculature growth depicted by VAM captures structural characteristics like vascular volume density, radii, mean distance to proximal neurons in the cortex. VAM-grown vasculature agrees with the experimental observation that the neural densities do not covary with the vascular density along the depth of the cortex but predicts a high correlation between neural areal density and microvascular density when compared over a global scale (across animals and regions). To explore the influence of neural activity on vascular arborization, the VAM was used to grow the vasculature in neonatal rat whisker barrel cortex under two conditions: (i) Control, where the whiskers were intact and (ii) Lesioned, where one row of whiskers was cauterized. The model captures a significant reduction in vascular branch density in lesioned animals compared to control animals, concurring with experimental observation.

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“…The astrocytic arborization is relatively less explored. A recent study [38] modelled the astrocyte morphology by forming Voronoi partitioning around randomly distributed seed points and matching the polygonal area patch from a given Voronoi partition to the closest astrocyte template extracted from experimental images of astrocytes. However, to the best of our knowledge, there are no published computational models that simulate the arborization of astrocyte processes.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model

Kumar

¹

,

Menon

²

,

G

³

et al. 2022

Preprint

View full text Add to dashboard Cite

Normal functioning of the brain relies on a continual and efficient delivery of energy by a vast network of cerebral blood vessels. The bidirectional coupling between neurons and blood vessels consists of vasodilatory energy demand signals from neurons to blood vessels, and the retrograde flow of energy substrates from the vessels to neurons, which fuel neural firing, growth and other housekeeping activities in the neurons. Recent works indicate that, in addition to the functional coupling observed in the adult brain, the interdependence between the neural and vascular networks begins at the embryonic stage, and continues into subsequent developmental stages. The proposed Vascular Arborization Model (VAM) captures the effect of neural cytoarchitecture and neural activity on vascular arborization. The VAM describes three important stages of vascular tree growth: (i) The prenatal growth phase, where the vascular arborization depends on the cytoarchitecture of neurons and non-neural cells, (ii) the post-natal growth phase during which the further arborization of the vasculature depends on neural activity in addition to neural cytoarchitecture, and (iii) the settling phase, where the fully grown vascular tree repositions its vascular branch points or nodes to ensure minimum path length and wire length. The vasculature growth depicted by VAM captures structural characteristics like vascular volume density, radii, mean distance to proximal neurons in the cortex. VAM-grown vasculature agrees with the experimental observation that the neural densities do not covary with the vascular density along the depth of the cortex but predicts a high correlation between neural areal density and microvascular density when compared over a global scale (across animals and regions). To explore the influence of neural activity on vascular arborization, the VAM was used to grow the vasculature in neonatal rat whisker barrel cortex under two conditions: (i) Control, where the whiskers were intact and (ii) Lesioned, where one row of whiskers was cauterized. The model captures a significant reduction in vascular branch density in lesioned animals compared to control animals, concurring with experimental observation.

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“…Large hubs eventually led to a dispersed population of intermediate-size hubs, which were still a few edge lengths away from the terminal nodes. Historically, astrocytes have been widely believed to have a 'sponge-like' or spongiform anatomy with a perforated architecture containing abundant holes and loops, and with presumably random organization (Arizono et al, 2020;Bushong et al, 2004;Savtchenko et al, 2018;Schiweck et al, 2018;Verisokin et al, 2021). This interpretation is largely based on impressions from light microscopy or lower resolution EM visualization of astrocytes and not founded on quantification of astrocytic shape in 3D space.…”

Section: Nanostructural Parts and Signatures Of Layer 2/3 Astrocytes In Mouse S1 Cortexmentioning

confidence: 99%

Organizing Principles of Astrocytic Nanoarchitecture in the Mouse Cerebral Cortex

Salmon

¹

,

Syed

²

,

Kacerovsky

³

et al. 2021

Preprint

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SUMMARYAstrocytes have complex roles in central nervous system (CNS) health and disease. Underlying these roles is an elaborate architecture based on frequent, extremely fine, but seemingly haphazard branches, as well as prominent features including tripartite synaptic complexes and perivascular endfeet. While broad categories of structures in astrocytes are known, the fundamental building blocks that compose them and their organizing principles have yet to be adequately defined. This is largely due to the absence of high-resolution datasets that can reveal nanoscopic features of astrocytes (i.e. 10-20nm diameter in x, y, and z) and a lack of computational approaches that can effectively interrogate astrocyte shape, organization, and nanoarchitecture. Here, we produced and analyzed multiple, high-resolution datasets of layer 2/3 mouse somatosensory cortex using focused ion beam scanning electron microscopy (8nm intervals) and computer vision approaches to provide a principled, quantitative analysis of astrocytic nanoarchitecture. A decomposition of astrocytes into fundamental ‘parts’ led to the discovery of unique structural components, recurring structural motifs, and assembly of parts into an organized hierarchy. New relationships were also discerned between astrocytic processes and other CNS microanatomy including mitochondria, tripartite synapses, and cerebrovasculature. By deploying computational resources to quantitatively understand the organizing principles and nanoarchitecture of astrocytes, this study reveals the specialized anatomical adaptations of these complex cells within the CNS.One Sentence SummaryUsing high-resolution serial electron microscopy datasets and computer vision, this study provides a systematic analysis of astrocytic nanoarchitecture from multiple samples of layer 2/3 of adult mouse neocortex, and presents quantitative evidence that astrocytes organize their morphology into purposeful, classifiable assemblies with unique structural and subcellular organelle adaptations related to their physiological functions.

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Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Cited by 32 publications

References 119 publications

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model

The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model

Organizing Principles of Astrocytic Nanoarchitecture in the Mouse Cerebral Cortex

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