Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 239-249).
The most fascinating function of the nervous system is its ability to generate consciousness, the subjective experience or qualia that distinguishes awake life from dreamless sleep. How consciousness is generated is an ancient philosophical question which has proven resistant to scientific analysis. While the human brain is known to generate consciousness, its complexity prevents acquisition of a mechanistic understanding of consciousness. Therefore, I chose to study the much simpler nervous system of the nematode Caenorhabditis elegans. I tested worms for a specific kind of learning, called trace conditioning, which correlates with conscious awareness in humans, under the assumption that if worms were able to trace condition, they might also be capable of conscious awareness. However, I was not able to show trace conditioning in worms, so the question of whether worms exhibit consciousness remains unresolved. In the process of using light in learning experiments, I noticed that worms stop feeding immediately after being exposed to short wavelength (UV) light. Curious about whether worms might actually have a subjective experience in response to light akin to primitive vision, I investigated the molecular and neural mechanisms that control this behavioral response. I identified the I2 pharyngeal neuron as a cellular light sensor required for the speed of feeding inhibition. Hydrogen peroxide elicited behavioral and cellular responses strikingly similar to those caused by light. The sensing of both light and hydrogen peroxide were mediated by the LITE-1 and GUR-3 proteins, both putative gustatory receptors, as well as by the conserved antioxidant enzyme peroxiredoxin PRDX-2. My results suggest that the LITE-1/GUR-3 family of receptors likely detects light through its generation of hydrogen peroxide or of another redox product. This is a novel mechanism by which light can be sensed. Additionally, by studying the worm's feeding response to light, I identified a pattern of neural function in which neurons appear to act independently to control sequential phases of a behavior. In the first phase, light rapidly inhibited feeding, with the I2 neuron sensing light and releasing glutamate likely onto pharyngeal muscle, where it was received by the AVR-15 glutamate-gated chloride channel. In the second phase, the inhibition of feeding was maintained via a circuit that included the extrapharyngeal neuron RIP and pharyngeal neurons I1 and MC. Finally, in the third phase, light stimulated pharyngeal contractions via the M1 neuron. These three circuits appear to be independent. I conclude that what initially appeared to be a simple reflex is instead a sequence of behavioral responses coordinated by independent neural circuits, suggesting a motif I term "parallel temporal tiling." Although I am still uncertain about whether worms have a subjective experience of light, this research will serve as a foundation for future work aimed at this very question.
by Nikhil Bhatla.
Ph. D. in Neuroscience