Introducing A Multi-Compartment Modeling Tool With the Potential to Analyze Branchpoint Propagation of Action Potentials Open Access

Abstract

This thesis presents a multi-compartment modeling tool implemented in Python that provides the flexibility and configurability needed to simulate action potential propagation in complex axon structures involving branch points and electrical coupling. The model’s development is motivated by the clinical significance of branch points in modulating sympathetic output and thus contributing to the pathophysiology of patients with spinal cord injuries (SCI). Sympathetic preganglionic neurons (SPNs) diverge to form axonal collaterals that synapse onto the sympathetic ganglionic chain with redundancy. The axonal branch points of such a complex network are susceptible to factors such as temperature undulations, axon geometry, and ion channel plasticity post-SCI, thereby causing conduction blocks in relaying action potentials through the sympathetic route. While similar simulation tools already exist, the significance of our model lies in its flexibility and specificity to our experimental studies on the topic. It allows for adjusting various parameters relating to axon dimensions and ion channel dynamics, which facilitates computational investigations of axonal modification of sympathetic signals. Using our modeling tool, we built two models–a Y-branch model simulating a main axon branch bifurcating into two daughter segments and a parallel-axon model with two axons coupled at the middle through gap junctions. Preliminary results were gathered to show the validity of our modeling tool and interesting observations of how axon geometry, temperature, and gGABA impact spike propagation across branch points.

Table of Contents

Introduction......................................................................................................................................1

Method.............................................................................................................................................5

Results............................................................................................................................................13

Discussion......................................................................................................................................27

References......................................................................................................................................29

Appendix........................................................................................................................................33

Figures

1.Illustration of integrating axial currents from neighboring    

compartments into the process of voltage update…………………............9

2.The Y-Branch model………………………………………………………........10

3.The parallel-axon model…………………………………………………….....12

4.Influence of temperature on branch point failure………………………...13

5.Impact of gGABA on branch point conduction block………………........15

6.Parallel-axon model (same as Figure 3 except with arrows added).…...16

7.Spike propagation with no gap junction conductance…………………....17

8.Spike propagation with low gap junction conductance……………….....18

9.Spike propagation with moderate gap junction conductance …………..20

10.Timing of spike propagation……………………………………………….....22

11.Effect of stimulus frequency on spike amplitude ………………………...24

12.Impact of extremely large gap junction conductance on spike

propagation…………………………………………………………………….........25

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Axon branch point multi-compartment axon model Axon
Committee Chair / Thesis Advisor	Prinz Astrid, Emory University
Committee Members	Sober Samuel, Emory University Hochman Shawn, Emory University Berman Gordon, Emory University

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