Specificity in Glia-Neuron Interactions

Abstract

Glia are important regulators of nervous system development and function. In both central and peripheral nervous systems, glia modulate neuron structure and function through a vast array of molecular mechanisms. One remaining question is whether a single glia regulates all its associated neurons in the same way. In this thesis, I answer this question using the cation chloride cotransporter KCC-3 in the amphid sheath (AMsh) glial cell of the model organism C. elegans. Briefly, I find that AMsh KCC-3 localizes to only one of the glia’s associated neurons, the thermosensory AFD neuron to regulate its shape and function. This localization is directed through repulsion by the cilia of other amphid neurons, and through two regions of the KCC-3 protein. First, a central sequence guides KCC-3 to apical-like adneuronal membrane, and then a C-terminal sequence localizes KCC-3 to a microdomain. In addition, I also collate our current knowledge of how peripheral glia use ionic regulation to modulate sensation. Together, this dissertation provides evidence and mechanistic details of glia-neuron specificity.