Cross-currents between Biology and Mathematics on Models of Bursting

Arthur Sherman (March 22, 2011)

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Abstract

I will trace the history of models for bursting, concentrating on square-wave bursters descended from the Chay-Keizer model for pancreatic beta cells. The model was originally developed on a biophysical and intutive basis but was put into a mathematical context by John Rinzel's fast-slow analysis. Rinzel also began the process of classifying bursting oscillations based on the bifurcations undergone by the fast subsystem, which led to important mathematical generalization by others. Further mathematical work, notably by Terman, Mosekilde and others, focused rather on bifurcations of the full bursting system, which showed a fundamental role for chaos in mediating transitions between bursting and spiking and between bursts with different numbers of spikes. The development of mathematical theory was in turn both a blessing and a curse for those interested in modeling the biological phenomena - having a template of what to expect made it easy to construct a plethora of models that were superficially different but mathematically redundant. This may also have steered modelers away from alternative ways of achieving bursting, but instructive examples exist in which unbiased adherence to the data led to discovery of new bursting patterns. Some of these had been anticipated by the general theory but not previously instantiated by Hodgkin-Huxley-based examples. A final level of generalization has been the addition of multiple slow variables. While often mathematically reducible to models with a one-variable slow subsystem, such models also exhibit novel resetting properties and enhanced dynamic range. Analysis of the dynamics of such models remains a current challenge for mathematicians.