A Framework for Understanding Small Nervous Systems

Abstract

How do we find important neurons and understand how their dynamics control behavior? Both of these are challenging and general problems in neuroscience. In this dissertation supervised by Sharad Ramanathan, I developed a framework to efficiently search for essential neurons and verify them individually using precise perturbations and measurements. I applied this framework to the small nervous system of the nematode C. elegans and uncovered neurons that control speed. Working with Dr. Ching-Han Shen, Dr. Josselin Milloz, and Tim Hallacy I screened through 41 transgenic lines that covered more than 82% of the nematode nervous system and uncovered a sparse set of three neurons which affect speed when inhibited. To measure their dynamics in freely moving animals, I worked with Dr. Askin Kocabas and Abdullah Yonar to develop a real-time image stabilization microscope that enabled me to stimulate individual neurons and probe their dynamics on the order of an hour which previously was not possible. I also developed a frequency division multiplexing imaging system which can read out pixel information faster than traditional CCD cameras. Using these tools, I showed that the dynamics in the sparse uncovered neurons were correlated with speed and also observed novel slow dynamics on the scale of tens of minutes in several other neurons. In summary, this study provides a framework to identify and study circuits essential for controlling behaviors in small nervous systems.