Advisory Committee Chair
Advisory Committee Members
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
A major challenge in neuroscience is understanding how the different neural cell types work together to process information and produce a behavioral output. Glial cells of the human brain have long been thought to act as support for the fundamental cell to cell communication at the core of cognition: neuronal synaptic communication. Research over the past several decades measuring glial activity and experimentally controlling glial cells in rodent model systems has shown that the two macroglia sub-types of glial cells (astrocytes and oligodendrocytes) have active roles in establishment, maintenance, and modulation of synaptic communication in the mammalian brain. Much of this research has utilized cell-type specific promoters to identify and genetically manipulate mammalian glial cells to better understand their role in intercellular communication in the brain. My research is aimed at examining the glia of C. elegans : a model organism chosen for a reductionist approach to research on how gene products and gene regulation work in development and function of a simple nervous system. I chose to focus on a subset of glia in this nematode, the sheath glia of the cephalic sensilla, due to cellular characteristics unique to this invertebrate and their morphological similarity to mammalian astrocytes and oligodendrocytes. I hypothesized that as the most evolutionarily ancient proto-astrocytes with some oligodendrocytes characteristics, these glia of C. elegans would exhibit a hallmark of mammalian glia: robust calcium dynamics upon stimulation. To test this hypothesis, I determined experimental applications for the hlh-17 gene promoter that would avoid confounding effects on behavior and used it to examine cultured C. elegans glia for the first time. I then adapted a genetically encoded calcium sensor to show that cultured glial cephalic sheath cells respond to membrane depolarization with increases in cytoplasmic calcium. I show that voltage-gated calcium channels underlie this response, indicating that glia of C. elegans have taken on a functional profile less like that known for mature mammalian glial cells but with some remaining commonalities. This establishes C. elegans as a model organism that can be used to study glia in a simple nervous system through contrast and comparison with macroglia of mammalian model organisms with similarities possibly representing ancient roles of glia and differences possibly representing roles taken on to meet demands imposed by a more complex nervous system.
Stout, Randy Franklin, "Calcium Dynamics Of Glial Cells And Genetic Influences On Behavior Of The Nematode Caenorhabditis Elegans" (2011). All ETDs from UAB. 3052.