Date of Award

8-2011

Degree Name

MS in Biomedical Engineering

Department/Program

Biomedical and General Engineering

Advisor

Robert Szlavik

Abstract

This work focuses on modeling a demyelinated Hodgkin and Huxley (HH) neuron with Simulated Program with Integrated Circuit Emphasis (SPICE) platform. Demyelinating disorders affect over 350,000 people in the U.S and understanding the demyelination process at the cellular level is necessary to find safe ways to treat the diseases [9]. Utilizing a previous SPICE model of an electrically small cell neuron developed by Szlavik [32], an extended core conductor myelinated neuron was produced in this work. The myelinated neuron developed has seven active Nodes of Ranvier (nodes) separated by a myelin sheath. The myelin sheath can be successfully modeled with a resistive and capacitive network known as internodes. Both the Nodes of Ranvier and internode equivalent circuits were implemented in P-SPICE sub-circuit library files. Properties of the neuron can be changed in the library files to simulate neurons of different electrical or geometric properties. Using the P-SPICE code developed in this work, a myelinated neuron’s action potential was simulated and the action potential at each node was recorded. The action potential at each node was uniform in amplitude and pulse width. The conduction velocity of the action potential was calculated to be 57.15 m/s.

Demyelination can be modeled by decreasing the capacitance and increasing the resistance of the myelin [34]. Two demyelinated neuron models were simulated in this work. The first model had one internode segment demyelinated, and the second model was of three consecutive internode segments. The resulting conduction velocity was calculated for both simulations. For one and three internode segment demyelinated the conduction velocity was slowed to 44.15 m/s, and 27.15 m/s respectively. This model successfully showed that an HH neuron implemented in SPICE could show the effects of demyelination on conduction velocity

The goal of this work is to develop a demyelinated neuron so that treatments for Multiple Sclerosis (MS) and other demyelinated neurons could be simulated to test various treatments’ effectiveness. A current treatment for MS is ion channel blockers. Future work would be to use this model to test current ion channel blocker therapy and to validate if such therapies alleviate conduction slowing.

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