Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

Christopher Fang-Yen

Second Advisor

Vijay Balasubramanian

Abstract

Understanding the neuronal control of movement has been a central goal of neuroscience for decades. In many organisms, chains of neural oscillators underlie the generation of coordinated rhythmic movements. However, the sheer complexity of spinal locomotor circuits has made understanding the mechanisms underlying rhythmic locomotion in vertebrates challenging. The roundworm C. elegans generates rhythmic undulatory movements that resemble those of swimming vertebrates, but using only a few hundred neurons. The relative simplicity of this organism has allowed a complete synaptic map of the nervous system to be developed. Moreover, C. elegans has a three-day life cycle and is amenable to a powerful battery of genetic techniques that allow the molecular basis of circuit functions to be probed much more rapidly than is possible in more complex organisms. Because of these advantages, C. elegans offers the possibility of understanding the network, cellular, and molecular principles of rhythmic locomotion in deeper detail than has been possible in any other model organism. However, it is currently unclear where in the C. elegans motor circuit rhythms are generated, and whether there exists more than one rhythm generator. I used optogenetic and lesioning experiments to probe the nature of rhythm generation in the locomotor circuit. I found that rhythmic activity in different parts of the body can be decoupled by both methods, implying that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, I localized at least two rhythmic sources to a network of cholinergic motor neurons that are distributed along the body. Moreover, I used rhythmic optogenetic manipulations to show that imposed rhythmic signals in any portion of the motor circuit can entrain oscillatory activity in the rest of the body, suggesting bidirectional coupling within the motor circuit. This organization, in which distributed oscillating circuits exist along the body but are closely linked by bidirectional coupling, is found in wide range of vertebrate and invertebrate animals. My results show that the functional architecture of the C. elegans motor circuit is highly analogous to that of much more complex organisms.

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