| Summary: | Neurotransmitter signalling to neurons and glial cells plays a key role in brain development, information processing and pathological processes. This thesis focuses on neurotransmitter signalling to oligodendrocytes, the glial cells which provide myelin to speed the propagation of action potentials along neuronal axons. In cerebellar and corpus callosal slices, I used patch-clamping and immunocytochemistry to examine the properties of precursor, immature and mature oligodendrocytes, characterizing their morphology and basic electrical properties, their response to glutamate, GABA and other neurotransmitters, and the neurotransmitter receptor subunits that they express. In contrast to the currently held view, I found that oligodendrocytes express NMDA receptors. These receptors show extremely weak magnesium-block, allowing them to be activated at the resting potential, and they may be composed of NR1, NR2C and NR3 subunits. To investigate the role of these NMDA receptors in pathology, experiments on hippocampal neurons were first used to establish how best to block glycolytic and mitochondrial production of ATP to mimic the energy deprivation which occurs in ischaemia. Ischaemia-evoked glutamate release was found to activate oligodendrocyte NMDA and non-NMDA receptors. Although the normal role of the oligodendrocyte NMDA receptors may be to regulate myelination, they probably contribute to the glutamate-mediated damage which occurs to oligodendrocytes in periventricular leukomalacia (leading to cerebral palsy), stroke, spinal cord injury and multiple sclerosis. Block of these receptors may therefore offer a potential therapeutic approach to treating these disorders.
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