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Title: Development of, and signalling to, oligodendrocytes and their precursors
Author: Clarke, L. E.
ISNI:       0000 0004 2728 3477
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Oligodendrocytes myelinate axons in the CNS to increase the speed of action potential conduction. Myelinating oligodendrocytes develop from oligodendrocyte precursor cells (OPCs). OPCs can express voltage-gated sodium and potassium channels, and receive excitatory and inhibitory synaptic input from axons. The functional relevance of voltage-gated and synaptic currents in OPCs is unknown, but electrical signalling from axons might regulate OPC development and myelination. In this thesis I investigate the electrical properties of OPCs, and how signalling to these cells regulates their proliferation, differentiation and myelination. I studied the electrical properties of OPCs in different brain areas, to investigate whether their electrical properties differ between embryonic sites of origin (in dorsal versus ventral parts of the CNS), and between brain regions (white matter versus grey matter). Firstly, using a dual reporter mouse line to colour code ventrally- and dorsally-derived oligodendrocyte lineage cells, I demonstrated that oligodendrocyte lineage cells derived from different embryonic sites are electrically similar. However, despite having indistinguishable electrical properties, dorsally-derived oligodendrocytes myelinated specific tracts in the spinal cord. Secondly, I have shown that OPCs in different brain regions have a similar expression of ion channels and precursor proteins, are all mitotically active, and generate differentiated oligodendrocytes but not neurons. Finally, having determined that all OPCs apparently have similar membrane properties, I investigated whether the inhibitory neurotransmitter GABA can regulate OPC proliferation, differentiation and myelination. I found that both oligodendrocytes and their precursors respond to GABA via the activation of GABAA receptors. In addition, endogenously released GABA was found to reduce the number of oligodendrocyte lineage cells formed, reduce the amount of myelin per axon and increase internode length. These results demonstrate that GABA, presumably released from inhibitory interneurons, can regulate myelination, and raise the possibility that GABA could also modulate CNS remyelination.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available