Mechanisms of Glial Pruning

Abstract

Glia are important regulators of nervous system function. In both peripheral and central nervous systems, glia regulate the connectivity of neural circuits by engulfing and degrading synapses and sensory structures with low activity. This process, here termed glial pruning, is a fundamental developmental method for producing robust neural circuits. More recently, glial pruning has been found to contribute to the physiological function of the nervous system. For instance, pruning has been shown to contribute to aspects of learning and memory. Altered regulation of pruning is evident in several neurological diseases, including in some neurodegenerative disease, but the mechanisms that drive this process and how they are mis-regulated in disease is an area of active research. In this thesis, I will review the current knowledge of glial pruning across animal systems as well as highlight my findings using the free-living nematode C. elegans to uncover the molecular mechanisms that drive this process. Briefly, we found that glia in C. elegans prune the specialized thermosensory ending of a sensory neuron in response to lowered neuron activity. We showed that glia can autonomously regulate the levels of engulfment and alterations in engulfment cause neuronal dysfunction. Furthermore, I describe a mechanism by which a Parkinson’s disease associated protein regulates this process in C. elegans. Together, this work demonstrates a complex molecular pathway that allows a glial cell to tune neuron function via pruning.