Publication Date
2022
Document Type
Dissertation
Committee Members
Sherif M. Elbasiouny, Ph.D. (Advisor); Caroline Cao, Ph.D. (Committee Member); Ulas Sunar, Ph.D. (Committee Member); Dan Halm, Ph.D. (Committee Member); Seif Eldawlatly, Ph.D. (Committee Member)
Degree Name
Doctor of Philosophy (PhD)
Abstract
Since Hodgkin and Huxley’s discoveries in the 1950s, mathematical modeling became an indispensable tool in neuroscience. The evolution of computer systems paved the way for computational models to improve our understanding of the nervous system. The long-term goals of this research are to develop tools for examining, understanding, and analyzing experimental data from spinal motoneurons (MNs), which are implicated in many motor disorders. Specifically, I developed high-fidelity, anatomically-detailed computational models that could be used to 1) study the cellular mechanisms underlying the non-linear MNs firing behaviors, 2) analyze the multifactorial process of MNs excitability regulation, and how it is affected by various cellular properties, and 3) identify biomarkers for early diagnosis of MNs disorders /diseases (e.g., ALS). Given the role of dendritic channels in modulating MNs excitability, the first aim of this dissertation work was to predict the spatial distribution of these channels in MNs, and how these channels affect the cell firing behavior. my simulations suggest that dendritic channels (L-type Ca2+ and SK) are likely located distal from the soma, and expressed in a punctate pattern, which provides a functional advantage to enhance synaptic inputs. Because it is empirically unfeasible to separate the currents of different SK channel isoforms. the second aim of this dissertation was to develop channel models for the SK2 and SK3 isotypes My simulations suggested that these two isoforms have different kinetic properties, which explains why a unified model for SK channels wouldn’t be accurate in simulating its currents. In the last aim of this dissertation, I developed high-fidelity MNs cell models to estimate the error in measured electrical properties that may result from truncating MNs dendrites in the slice preparation. my simulations show that slice preparation methods induce variable errors across the different measured properties, specifically dendritic channels measurements were higher (40%) than somatic ones. This explains one factor contributing to the different results from the slice vs whole cord preparations. To conclude, the results of this dissertation work provide insights about MN excitability mechanisms, advance simulation platforms to develop better algorithms for prosthetic control, and also aid with identifying biomarkers for early ALS diagnosis.
Page Count
236
Department or Program
Ph.D. in Engineering
Year Degree Awarded
2022
Copyright
Copyright 2022, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may not be modified. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
ORCID ID
0000-0002-9460-378x
