Student Theses and Dissertations

Christine Cho

Date of Award

2015

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Bargmann Laboratory

Abstract

Animals live in constantly changing environments with fluctuating resource availability and hazardous threats. By gathering information from past experiences, individuals modify their behavioral response to adapt to the changing environment, a phenomenon known as “experience-dependent plasticity”. This ability to change is a crucial for survival, and how an organism achieves this adaptive plasticity is a question of much interest. Research in the field has yielded insight into how changes in connectivity within the brain can drive changes in behavior. Understanding the neural mechanisms of plasticity not only satisfies intellectual curiosity, but also provides a basis for understanding pathological conditions that come from excessive or insufficient plasticity. With a well-characterized nervous system, stereotyped behaviors, and an armory of molecular and genetic tools, C. elegans is well-suited for the study of experience-dependent plasticity. Using an olfactory adaptation paradigm in which animals lose attraction to butanone after it is paired with starvation, I here describe neuronal and molecular mechanisms that are associated with and necessary for plasticity in C. elegans. In Chapter 2, I report my findings on circuit mechanisms of butanone adaptation, identifying neurons that are required for adaptation and changes in neuronal activity associated with adaptation. I show that an interneuron is required for adaptive changes in the olfactory sensory neuron. In particular, I show that nuclear translocation of a protein kinase, a process known to be necessary for adaptation, requires activity of the interneuron. This feedback from downstream neurons is transformed into changes in sensory properties. Using pharmacogenetic tools that allowed me to disrupt different parts of the circuit with temporal precision, I identified a group of neurons whose activity is required during adaptation. Finally, I performed functional calcium imaging of animals before and after adaptation, and determined that changes in neuronal responses to butanone can be detected at multiple sites within the circuit, starting as early as the as the sensory neurons. In Chapter 3, I describe the analysis of two genes, a G-protein β subunit and a K+ channel, that have different roles in adaptation. I used whole-genome sequencing and genetic mutations to identify the genes that are required for butanone adaptation, then characterized the odor-specificity of each gene. This analysis provides the basis for future work that should examine the molecular context in which these genes act and the impact they have on circuit mechanisms of adaptation.

Comments

A Thesis Presented to the Faculty of The Rockefeller University In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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