Sneyd 9706565 Intercellular calcium waves are a ubiquitous and crucial feature of intercellular communication, and perform a variety of physiological functions. Most intriguingly, intercellular calcium waves in mixed neuronal-glial cultures have been observed passing from glial cells to neurons, and thus they may possibly have an important role to play in information processing. The investigator uses mathematical models to study the mechanisms involved in intercellular calcium waves. The first part of the work involves the study of the mechanisms underlying intracellular calcium oscillations and waves in epithelial and glial cells. Secondly, in light of recent experimental evidence, previous models are modified and used to study the mechanisms of intercellular calcium wave propagation in glial cell cultures. Finally, in hippocampal explant cultures the intercellular calcium waves show a remarkable degree of spatial organisation, forming propagating plane waves and rotating spirals. The model is used to determine the mechanisms by which intracellular calcium waves can be coupled on a much larger space scale to form intercellular calsium waves with such a high degree of self-organisation. Waves of calcium that travel between cells are one important way in which cells can signal to their neighbours. Such intercellular communication, although not yet well understood, is known to play a vital role in many physiological processes. For instance, the response of an epithelial cell layer to a wound is governed (at least in part) by an intercellular calcium wave, while, in the brain, waves of calcium can travel from glia to neurons, and vice versa. Thus, calcium waves very likely have an important role to play in information processing. For these reasons, there is a great deal of interest in studying the mechanisms that underly such waves. Mathematics has an important role to play in these studies. By its very nature, wave propagation is a complex phe nomenon, not easily understood by intuition alone. Although mathematics cannot provide answers to all pertinent questions, when used in conjunction with experimental results, it can be used to interpret and understand existing results, while directing the course of future experimemtal studies. The investigator (a mathematician) and his experimental colleagues propose a coordinated series of theoretical and experimental investigations that will lead to a greater understanding of how glial cells communicate by means of calcium waves, and how such communication can coordinate activity over large regions of the hippocampus. Funding for the project is provided by the program of Applied Mathematics and the Office of Multidisciplinary Activities in MPS and by the Computational Neuroscience program in BIO.
