Defense Date

2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Neuroscience

First Advisor

Dr. Young-Jai You

Second Advisor

Dr. Andrew Larner

Third Advisor

Dr. Babette Fuss

Fourth Advisor

Dr. Andrew Davies

Fifth Advisor

Dr. Carmen Sato-Bigbee

Abstract

Feeding behavior and its associated neural circuitry is complex and intricate in mammalian systems, however, a simple model organism, such as C. elegans provides a more basic approach to understand factors and molecules involved. The fruit-dwelling nematode provides a unique set of resources; it only consists of 959 cells, 302 of which are neurons. In addition, each neuron’s connectivity and position within the worm is known and consistent between animals. Conservation of neurotransmitters and biochemical processes add to this impressive list. These resources provide an excellent background to address feeding behavior and the neural structures governing it.

Feeding behavior in worms mimics feeding behavior in more complex organisms. They decide when to eat based on recent feeding behavior, current nutritional status, availability of food, and familiarity with the food available. Following starvation and refeeding worms enter a behavioral state similar to post-prandial sleep. The worms will stop eating and stop moving, in a state referred to as satiety quiescence. The ability to enter this state and maintain it is dependent on a pair of neurons in the head of C. elegans called ASI. Using calcium imaging and an automated satiety quiescence assay, our lab has found that this neuron pair is important for entering satiety quiescence and senses food. Feeding behavior, such as satiety quiescence, is regulated by numerous factors internal and external to the worm. Another pair of head neurons, ASH are capable of suppressing ASI’s activity in the presence of noxious stimuli and the presence of nutrients (potentially acting via ASI) can suppress ASH’s activation to noxious stimuli under starvation conditions.

The interaction between these two neuron pairs can be regulated by other signals from the rest of the worm. We identified an opioid signal that can modulate the response of ASI to noxious stimulus signaling from ASH under starvation conditions. Other signals were identified to influence satiety behavior and this circuit including serotonin, octopamine, glutamate, and adenosine. In addition to these signals, a group of transcription factors were identified that may play a role in conveying the status of fat storage within the worm to its nervous system. Nuclear hormone receptors were found to increase their expression during starvation then decrease their expression upon refeeding. Upon completion of this work, we have a reached a greater understanding of the internal and external conditions governing feeding and avoidance behaviors.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-11-2016

Available for download on Monday, May 10, 2021

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