| Biologically-created electric fields hold the potential to regulate a variety of cellular processes which underlie fundamental cell function. This dissertation explores the potential role of such electric fields in central nervous system (CNS) development. Astrocytes receive particular emphasis in our discussion due to their role in regulating many aspects of CNS development. For example, astrocytes arrange their processes in an organized fashion during development and create a structural framework, which consequently serves as a guide to axon growth. Interestingly, cultured astrocytes organize their processes in a highly oriented fashion upon exposure to electric fields of physiologic strength. We demonstrate that the electrically aligned astrocyte can serve as a substrate capable of directing the growth of cultured dorsal root ganglion neurons. Furthermore, we show that the length of neurite extension is enhanced on electrically aligned astrocytes in comparison to those that are randomly oriented. These results support the idea that the alignment of astrocytes in vivo could be due to the presence of endogenous electric fields.;In addition to guiding cells and axons with their processes, astrocytes have also been shown to direct the migration of a variety of cell types by secreting tropic factors. One such cell, the oligodendrocyte progenitor, migrates during the embryonic period to a fiber tract in need of myelination. We examined the migration of oligodendrocyte progenitor cells in a developmental model of the optic nerve. During development and in our model system, the initiation of progenitor cell migration is coincident with events involving neuronal electrical activity. By silencing the electrical activity in the optic nerve with intraocular injections of a sodium channel blocking agent, tetrodotoxin, we demonstrate reduced progenitor cell migration into the optic nerve. These results suggest progenitor cell migration depended on retinal electrical activity. Utilizing in vitro techniques, we also provide evidence that electrical activity induces astrocytes to produce tropic factors capable of stimulating progenitor cell migration. Together, these studies support the idea that electric fields provide directional cues in the developing central nervous system which can guide the growth of axons and migrating progenitor cells to their destination. |
