Neural-Glial Communication Networks: A Computational Approach

Ohio University, Athens OH

Investigators

Abstract

The emerging picture of brain function is that of a complex communication network between neurons and astrocytes. It has now become clear that astrocytes - the most numerous types of non-neuronal cells in the brain - are important partners to the neurons. Astrocytes listen to the neuronal chatter, respond to it and talk back to the neurons, thus modulating their functions. Understanding the complex communication network of neurons and astrocytes is therefore significant for the understanding of the brain. While this emerging field of research has been driven so far predominantly by methods of cellular and molecular biology, the main objective of this project is to add a new set of tools - mathematical and computational modeling - that can offer new avenues to explore the complex neural-glial communication network. A mathematical/computational model - consisting of functional coupled units - generates a unique conceptual framework that allows categorizing biologic processes and generating predictions. Specifically, this award will enable an exploration of the generation of signals in astrocytes in response to neuronal activity, the spatial spread of the signal through the network of astrocytes, and the effect of the spreading signal back on the neuronal circuit, all significant aspects of interactions between neurons and astrocytes. Realistic mathematical models of these interactions will be developed. After the significant components of the neural-glial communication system are understood, neuronal circuitry with an architecture resembling that in the cortex can be modeled, and the influence of astrocytes on the network will be explored. These goals will be achieved through the use of modern imaging tools employed in a cell biologist's laboratory, from which critical data on intracellular calcium signaling will be used to develop realistic mathematical modeling of the neural-glial interactions. This project has significance far beyond the specific purpose of understanding the communication network of astrocytes and neurons in the central nervous system. Quantitative and conceptual understanding of neural-glial interactions may provide a basis for a better understanding of brain disorders such as migraine and epilepsy, in which a glial component is strongly suspected. Additionally, understanding of the intracellular calcium signaling, an important signaling pathway between astrocytes, is of critical importance for signaling in a variety of tissues, such as liver, where it contributes to the release of enzymes, and in corneal and bronchial epithelia where it is involved with wound response.