A Process for Digitizing and Simulating Biologically Realistic Oligocellular Networks Demonstrated for the Neuro-Glio-Vascular Ensemble

Abstract

One will not understand the brain without an integrated exploration of structure and function, these attributes being two sides of the same coin: together they form the currency of biological computation. Accordingly, biologically realistic models require the re-creation of the architecture of the cellular components in which biochemical reactions are contained. We describe here a process of reconstructing a functional oligocellular assembly that is responsible for energy supply management in the brain and creating a computational model of the associated biochemical and biophysical processes. The reactions that underwrite thought are both constrained by and take advantage of brain morphologies pertaining to neurons, astrocytes and the blood vessels that deliver oxygen, glucose and other nutrients. Each component of this neuro-glio-vasculature ensemble (NGV) carries-out delegated tasks, as the dynamics of this system provide for each cell-type its own energy requirements while including mechanisms that allow cooperative energy transfers. Our process for recreating the ultrastructure of cellular components and modeling the reactions that describe energy flow uses an amalgam of state-of the-art techniques, including digital reconstructions of electron micrographs, advanced data analysis tools, computational simulations and in silico visualization software. While we demonstrate this process with the NGV, it is equally well adapted to any cellular system for integrating multimodal cellular data in a coherent framework.

Interactive visualization and analysis of morphological skeletons of brain vasculature networks with VessMorphoVis

“…Although all are generally due to cerebral hemodynamic insufficiencies of one sort or another, there is still little etiological or diagnostic agreement about causes or precise definitions, let alone treatments ( Frantellizzi et al , 2020 ). The neuro-glia-vasculature (NGV) ensemble is often considered as a functional unit for the study of interactions among these critical components of brain energy metabolism at an oligocellular scale ( Coggan et al , 2018b ; Jolivet et al , 2015 ). Within this unit, detailed vascular maps revealing fine anatomical features of vessels and their interaction with neurons and glia are therefore critical to understanding overall brain function ( Calcinaghi et al , 2013 ; Calì et al , 2019 ; Coggan et al , 2018a ; Marín-Padilla, 2012 ; Schmid et al , 2019 ).…”

A Method for 3D Reconstruction and Virtual Reality Analysis of Glial and Neuronal Cells

“…The first proposed model for an electron microscopy setup allowing automated serial section and imaging dates back to 1981 1 ; the diffusion of such automated, improved setups to image large samples using EM increased in the last ten years 2,3 , and works showcasing impressive dense reconstructions or full morphologies immediately followed 4,5,6,7,8,9,10 .…”

Interactive Volumetric Visual Analysis of Glycogen‐derived Energy Absorption in Nanometric Brain Structures

“…We plan to use the framework for supporting other studies involving glycogen effects in the central nervous system, like learning [ACD*18], the sleep‐wake cycle [BdVK*18], and the development of neurodegenerative diseases. Current limitations are related to data preprocessing which, at current stage, requires time‐consuming human efforts, especially for dense reconstruction of neural structures from EM data [CCK*18]. This partially limits the usage of the framework to ad hoc custom ultrastructural studies.…”

“…Starting from electron microscopy images, generating labels which associate each pixel to a specific neural structure is a general task performed by domain scientists to support ultra‐structural studies. In this work, we considered a hybrid pipeline [CCK*18] involving a first, rough automatic segmentation that runs offline, performed through iLastik tool [SSKH11], for finding the gross features and processes of a cell. This first segmentation is then followed by a manual proofreading phase, performed through TrackEm2 tool [CSS*12], for specifying exact boundaries and finer details.…”