Document Type

Dissertation

Date of Degree

Summer 2014

Degree Name

PhD (Doctor of Philosophy)

Degree In

Applied Mathematical and Computational Sciences

First Advisor

Colleen C. Mitchell

Abstract

Auditory physiology is nearly unique in the human body because of its small-diameter neurons. When considering a single node on one neuron, the number of channels is very small, so ion fluxes exhibit randomness.

Hodgkin and Huxley, in 1952, set forth a system of Ordinary Differential Equations (ODEs) to track the flow of ions in a squid motor neuron, based on a circuit analogy for electric current. This formalism for modeling is still in use today and is useful because coefficients can be directly measured.

To measure auditory properties of Firing Efficiency (FE) and Post Stimulus Time (PST), we can simply measure the depolarization, or "upstroke," of a node. Hence, we reduce the four-dimensional squid neuron model to a two-dimensional system of ODEs. The stochastic variable m for sodium activation is allowed a random walk in addition to its normal evolution, and the results are drastic. The diffusion coefficient, for spreading, is inversely proportional to the number of channels; for 130 ion channels, D is closer to 1/3 than 0 and cannot be called negligible.

A system of Partial Differential Equations (PDEs) is derived in these pages to model the distribution of states of the node with respect to the (nondimensionalized) voltage v and the sodium activation gate m. Initial conditions describe a distribution of (v,m) states; in most experiments, this would be a curve with mode at the resting state. Boundary conditions are Robin (Natural) boundary conditions, which gives conservation of the population. Evolution of the PDE has a drift term for the mean change of state and a diffusion term, the random change of state.

The phase plane is broken into fired and resting regions, which form basins of attraction for fired and resting-state fixed points. If a stimulus causes ions to flow from the resting region into the fired region, this rate of flux is approximately the firing rate, analogous to clinically measuring when the voltage crosses a threshold. This gives a PST histogram. The FE is an integral of the population over the fired region at a measured stop time after the stimulus (since, in the reduced model, when neurons fire they do not repolarize).

This dissertation also includes useful generalizations and methodology for turning other ODEs into PDEs. Within the HH modeling, parameters can be switched for other systems of the body, and may present a similar firing and non-firing separatrix (as in Chapter 3). For any system of ODEs, an advection model can show a distribution of initial conditions or the evolution of a given initial probability density over a state space (Chapter 4); a system of Stochastic Differential Equations can be modeled with an advection-diffusion equation (Chapter 5). As computers increase in speed and as the ability of software to create adaptive meshes and step sizes improves, modeling with a PDE becomes more and more efficient over its ODE counterpart.

Keywords

action potential, auditory nerve fiber, partial differential equation, population model, probability density function, separatrix

Pages

xii, 83 pages

Bibliography

Includes bibliographical references (pages 81-83).

Copyright

Copyright 2014 Rebecca Elizabeth Gasper

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