Quantifying the Behavioral Response to Optogenetic Stimulation of Mechanosensory Neurons in C. elegans

Abstract

This thesis looks at the relationship between the neural activity and the behavior of a freely moving roundworm Caenorhabditis elegans. We optically activate two mechanosensory neurons in vivo and use advanced image and statistical analysis to quantify the behavior, and consequently the behavioral changes that arise due to the perturbation of the neurvous system. We outline the procedure to measure and identify behaviors in a lower dimensional space, which allows us to explain the consequences of the activity of specific neurons, and to potentially use this analysis to further investigate functional structure of the animal nervous system. Despite technological advances, the ways in which animal brains function remain elusive due to the complexity of most animal nervous systems. The structure of most brains is also rarely well known. Our model organism has one of the best researched nervous systems in the animal kingdom. C. elegans is a transparent nematode whose brain structure has been studied in detail [29] and all of its 302 neurons and their connections have been identified. Yet, we still have only a limited knowledge of the neural dynamics and functions that specific neurons perform. One of the most interesting scientific questions today is how does the brain activity correlate with the behavior. Many experiments have been done in this field, like that of Sawin [21], but so far they have relied on subjective categorizations of behavior. We employ dimensionality reduction by Principal Component Analysis to objectively and mathematically categorize the most important components of animal behavior robustly [23, 25, 26, 27]. We find that the laser stimulation of the OLQ and CEP neuron alters the values of behavioral components we measure in a complex way, illustrating a non-trivial relationship between the activity of these two neurons and the motor activity of C. elegans. Moreover, we identify the behavior that the optogenetic stimulation of CEP neuron causes. Our ability to reconstruct the exact behavioral response thus draws a strong quantitative connection between the brain activity and behavior of C. elegans.