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.