Network topology analysis of the C. elegans connectome

Abstract

This thesis aims to uncover the functional design principles of nervous systems. To reach this aim, it is useful to examine a complex nervous system that is both well specified and highly tractable, making the nematode roundworm Caenorhabditis elegans an attractive model system, especially since it is the only complete connectome currently available for analysis in the cell level. In this computational study, I assessed the network topological properties of the C. elegans connectomes using graph theoretic approaches with the following three topics:

1. Vulnerability-based critical constituents of the hermaphrodite C. elegans connectome 2. Vulnerability-based critical constituents of the male C. elegans connectome 3. Asymmetry of the hermaphrodite C. elegans connectome

For the vulnerability studies, I tested the effects of individual attacks on every neuron and synaptic connection in the hermaphrodite and the male C. elegans connectomes to identify and characterize the most critical constituents of the network by quantifying the changes in key network properties of the connectomes that influence information processing. My analysis identified 12 neurons and 29 synapses of the hermaphrodite connectome and 9 neurons and 33 synapses of the male connectome that were critical to clustering, information integration and propagation. These critical constituents formed circuit-level structure to control the C. elegans connectomes. Furthermore, the biological functions of the critical constituents were related to dealing with adverse conditions and mating behaviors (hooking and backing during vulva search). My results suggest that the biological functions should be critical factors for negotiating among efficiency, wiring cost, and vulnerability to build the connectome structures. For the asymmetry study, I tested the differences of the neuronal pairs in the hermaphrodite connectome using graph theoretic measures. My results suggest the possibility of the differences in biological functions of neuronal pairs considered as symmetric pairs. We believe our study provides a significant advance in the understanding of the network topology of the C. elegans connectomes, and provides insights into the fundamental architectural design of complex nervous systems and the approaches to understanding their biological functions.