Glial cells represent the most abundant cell population in the central nervous system (CNS), and yet, have historically been thought of as merely support cells for neurons. Over the past few decades, however, the number of identified roles that glial cells play in the CNS has expanded at an exponential rate, revealing new and exciting functions in neuron-glial communication. At synapses, astrocytes are now recognized as part of a "tripartite" complex with pre- and postsynaptic structures and can modulate synaptic transmission and plasticity. Accumulating evidence has also revealed new roles for oligodendrocytes in regulating axon diameter and integrity, and ion channel clustering. Despite our knowledge of the physiological connections between neurons and glia, relatively little is known about the morphological interplay of these cells during development and in the mature brain. The results presented in this thesis reveal the extent and time-course of rapid remodelling of astrocytes and oligodendrocytes in close proximity to dendritic spines and axons respectively. These findings provide further evidence that glia play an important role in regulating the structural plasticity of the brain. The methodology developed also provides a powerful system for the study of neuron-glial structural dynamics and may contribute to the development of novel therapeutic strategies for diseases affecting the central nervous system.

Myelin plays an essential function in the behaviour of higher organisms by increasing the speed of axonal conduction. Indeed, myelin deficiency or damage can lead to serious motor and sensory dysfunction. In the central nervous system, myelin is produced by a specialized macroglial cell known as the oligodendrocyte. Although much is known about oligodendrocytes with respect to their role in myelin production, many details regarding their development and maintenance still remain unclear. These details may be of great importance for fully understanding the fundamental properties of oligodendrocytes and for devising strategies for treating myelin-related diseases. In this thesis, we report the development of a system using organotypic hippocampal slices, viral gene delivery methods, immunostaining techniques and confocal imaging that can be used to study the properties of oligodendrocytes and myelin. This system preserves many features of the intact brain and can be used to investigate cells of the oligodendrocyte lineage at different developmental stages. Individual oligodendrocytes were targeted using this system and we showed that they can be induced to express various proteins, such as proteolipid protein and neurofascin-155, that localized to specific compartments of oligodendrocytes. This system was then used to address the importance of glutamate receptor signalling on myelin. Studies were performed at the light microscopic level using agonists and antagonists of ionotropic glutamate receptors. Myelin showed progressive pathology over the course of hours following exposure to glutamate receptor agonists and, interestingly, glutamate signalling was not essential for myelin maintenance over a 48 hour period. This thesis work thus describes the use of a novel system that can help analyze both the cellular and molecular aspects of oligodendrocyte development and maintenance.

No description available.

No description available.